@article {pmid41545303,
year = {2026},
author = {Huang, JJ and YousefiAsl, M and Singh, N and Grivas, P and Bhatia, S},
title = {Steroid-sparing strategies for managing immune-related adverse events.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {1},
pages = {},
doi = {10.1136/jitc-2025-013776},
pmid = {41545303},
issn = {2051-1426},
mesh = {Humans ; *Neoplasms/drug therapy/immunology ; *Immune Checkpoint Inhibitors/adverse effects ; *Drug-Related Side Effects and Adverse Reactions/drug therapy/etiology ; *Steroids/therapeutic use ; *Immunotherapy/adverse effects/methods ; },
abstract = {Although immune checkpoint inhibitors (ICI) have greatly improved outcomes in several cancer types, their use is also associated with immune-related adverse events (irAEs) that can impact any organ system and lead to significant morbidity and even mortality. Current approaches to treatment of irAEs largely rely on the use of systemic corticosteroids, which can compromise antitumor immune responses and oncologic outcomes. Prolonged use of systemic corticosteroids is also associated with its own set of toxicities. Thus, there is a critical need for steroid-sparing treatment approaches for irAEs.In this article, we review the literature for alternative therapeutic approaches for irAEs, which include targeted delivery (alternate routes of administration) of steroids (eg, budesonide) as well as systemic non-steroidal strategies using other mechanisms of action, such as integrin/cytokine blockade, antibody depletion, disease-modifying antirheumatic drugs and fecal microbiota transplant, among others. Many of these approaches have shown significant promise in their ability to induce a clinical response and improve symptoms, even in the setting of steroid-refractory or steroid-dependent irAEs. These approaches are being increasingly used as primary and secondary prophylaxis in patients at high risk of irAEs. Importantly, these strategies may mitigate steroid-associated toxicities, preserve antitumor immune responses and allow continuation of ICI after development of irAEs, hence enabling the full potential of ICI against cancer.},
}

Humans
*Neoplasms/drug therapy/immunology
*Immune Checkpoint Inhibitors/adverse effects
*Drug-Related Side Effects and Adverse Reactions/drug therapy/etiology
*Steroids/therapeutic use
*Immunotherapy/adverse effects/methods

@article {pmid41544875,
year = {2026},
author = {Zuo, G and Chang, F and Yuan, X and Shen, Y and Guo, X and Tang, B and Huang, JA and Liu, Z and Lin, Y},
title = {Differential toll-like receptor 2 activation by Akkermansia muciniphila and Bacteroides thetaiotaomicron mediates the beneficial effects of Fu brick tea polysaccharide against colitis.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108100},
doi = {10.1016/j.phrs.2026.108100},
pmid = {41544875},
issn = {1096-1186},
abstract = {Fu Brick Tea Polysaccharide (FBTP) ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the key intestinal bacterial strains and downstream molecular mechanisms mediating these protective effects remain unclear. In this study, FBTP ameliorated colitis and concurrent liver injury in a microbiota-dependent manner, primarily by enriching Akkermansia muciniphila (A. muciniphila) and depleting Bacteroides thetaiotaomicron (B. thetaiotaomicron). The essential role of the microbiota was confirmed through fecal microbiota transplantation. Mechanistically, A. muciniphila synergistically employed both its microbe-associated molecular patterns (MAMPs) and metabolic activity to activate the toll-like receptor 2 (TLR2)-Akt anti-inflammatory signaling pathway, favorably modulating Treg/Th17 immune homeostasis. However, challenging its established status as a beneficial commensal, B. thetaiotaomicron was found to activate the TLR2-NF-κB pro-inflammatory pathway driven primarily by its MAMPs, significantly exacerbating colitis, bacterial translocation, and liver injury. The pivotal role of TLR2 in mediating these divergent bacterial outcomes was confirmed through gene knockdown experiments. In conclusion, this study reveals that FBTP restores immune homeostasis by orchestrating a complex, TLR2-dependent interplay between beneficial (A. muciniphila) and pathobiontic (B. thetaiotaomicron) bacteria. This discovery not only clarifies the therapeutic mechanism of FBTP but also highlights the context-dependent risk of key commensals, offering critical insights for developing more precise microbiota-targeted interventions.},
}

@article {pmid41543761,
year = {2026},
author = {Munira, MS and Stevens, JE and Shahin, W and Wang, K and Franks, AE and Perez, ARJ and Scott, JW and Hill-Yardin, EL},
title = {Towards treatments targeting the gut to improve behavioural outcomes in autism spectrum disorder.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {41543761},
issn = {1435-1463},
support = {APP2003848//National Health and Medical Research Council/ ; },
abstract = {Autism spectrum disorder (ASD; autism) is a prevalent and heterogeneous neurodevelopmental disorder characterised by social communication difficulties, repetitive behaviour, and restricted interests. For individuals with autism, in particular those who require substantial care-giver support, irritability, heightened sensitivity and aggressive behaviours in response to sensory, social, or environmental triggers can limit access to health, education and community services and impact quality of life. Although gastrointestinal (GI) symptom severity is associated with irritable behaviours in autism, there are few approved medications to address challenging behaviour or comorbid psychiatric disorders, or gut dysfunction in autism. Here, we review the mode of action of drugs undergoing clinical trials for treating irritable behaviour and improving social communication as well as potentially gastrointestinal symptoms in individuals with autism. Repurposed medications such as pimavanserin (an atypical antipsychotic) and the antiparasitic suramin are being trialled for treating irritable behaviours and impaired social interaction, respectively, in autism. NTI164 is a medicinal cannabis-derived biopharmaceutical undergoing clinical safety and efficacy trials for improving social communication and similarly, ML-004 is an investigational drug being assessed for treating social communication deficits. Two other repurposed medications previously utilised for schizophrenia; brexpiprazole and lumateperone, as well as AB-2004, a microbial metabolite sequestering agent (with proposed actions on gut function), are undergoing clinical trials to assess impacts on irritability associated with autism. We also outline emerging findings from clinical studies on the use of gut-targeted small molecules and bacteriophage therapy, prebiotics, probiotic supplementation and faecal microbiota transplantation (FMT), and their potential impact on behavioural symptoms in autism.},
}

@article {pmid41543263,
year = {2026},
author = {Baral, B and Parajuli, M and Pinilla, J and Muniz, J and Baral, B and Cançado, GGL},
title = {Safety and efficacy of oral microbiome therapy for the treatment of recurrent Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials.},
journal = {Scandinavian journal of gastroenterology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/00365521.2026.2616310},
pmid = {41543263},
issn = {1502-7708},
abstract = {INTRODUCTION: This systematic review and meta-analysis aimed to assess the safety and efficacy of oral microbiome therapy (OMT) for the treatment of recurrent Clostridioides difficile infection (CDI).

METHODS: A comprehensive search was performed in PubMed, Cochrane library, Scopus and Embase. All randomized controlled trials (RCTs) meeting predefined inclusion criteria were included. Statistical analysis was performed using R software.

RESULTS: Three RCTs comprising 469 patients were analyzed, of whom 250 (53%) received OMT and 219 (47%) received placebo. OMT significantly reduced CDI recurrence at week 8 compared to placebo (risk ratio [RR] 0.57; 95% confidence interval [CI] 0.33-0.99; p = 0.04). In exploratory efficacy analyses, no significant differences in recurrence were observed between groups when stratified by prior fidaxomicin use (RR 0.36; 95% CI 0.03-4.01; p = 0.40) or vancomycin use (RR 0.68; 95% CI 0.30-1.55; p = 0.35). Similarly, Firmicutes engraftment at week 1 (mean difference [MD] 41.78; 95% CI -10.55 to 94.11; p = 0.12) and week 8 (MD 34.06; 95% CI -2.49 to 70.61; p = 0.07) did not show statistically significant between-group differences. Safety outcomes and adverse events were comparable between OMT and placebo.

CONCLUSION: OMT seems to reduce CDI recurrence at week 8 compared with placebo while demonstrating a comparable safety profile, supporting its role as an effective, well-tolerated therapy for recurrent CDI. New studies are necessary to confirm these findings.

REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251022230.},
}

@article {pmid41541603,
year = {2026},
author = {Cheung, SLY and Kenway, LC},
title = {Pathophysiological Mechanisms and Nonpharmacological Interventions in Irritable Bowel Syndrome: Current Insights and Future Directions.},
journal = {Journal of nutrition and metabolism},
volume = {2026},
number = {},
pages = {4520019},
pmid = {41541603},
issn = {2090-0724},
abstract = {Irritable bowel syndrome, diagnosed using the ROME IV diagnostic criteria, is one of the most common dysfunctional disorders of the gastrointestinal system with a high global prevalence. Although symptom presentation is diverse, symptoms primarily manifest as abdominal pain, bloating, and alterations to bowel habits, negatively impacting quality of life but without an associated increase in mortality risk. Disruptions to the gut-brain axis, the bidirectional communication system between the central nervous system and the enteric nervous system, are hypothesised to be at the core of irritable bowel syndrome. Dysfunction may also be associated with stress and anxiety, as well as dietary factors, among other aspects related to physical and social environment, genetic predisposition and medical history. Patients with irritable bowel syndrome have also demonstrated increased vulnerability to neurotransmitter imbalances, with abnormalities associated with changes in gastrointestinal motility, low-grade inflammation and visceral pain. Moreover, chronic stress and anxiety may significantly exacerbate symptoms through the upregulation of cortisol secretion, disrupting the gut microbiome and elevating visceral sensitivity. While the gut microbiome maintains the integrity of the gut-brain axis and intestinal barrier, decreases in its diversity heighten susceptibility to intestinal inflammation. Although there is currently no known cure for irritable bowel syndrome, research supports stress management and behavioural therapies, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, and probiotic supplementation as key interventions to alleviate symptoms. Additionally, faecal microbiota transplantation emerges as a promising intervention that addresses some of the limitations in current interventions. This literature review explores the pathophysiological mechanisms relating to irritable bowel syndrome, with insight into current interventions and future directions to directly address the underlying factors driving symptomology.},
}

@article {pmid41540689,
year = {2026},
author = {Zhang, Y and Duan, Y and Zhang, C and Yu, L and Liu, Y and Xing, L and Wang, L and Yu, N and Peng, D and Chen, W and Wang, Y},
title = {[Poria cocos polysaccharide alleviates cyclophosphamide-induced intestinal barrier dysfunction and inflammation in mice by modulating gut flora].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {46},
number = {1},
pages = {34-46},
doi = {10.12122/j.issn.1673-4254.2026.01.04},
pmid = {41540689},
issn = {1673-4254},
support = {82505171 and 82204748//Natural Science Foundation for the Youth (NSFY) of China/ ; },
mesh = {Animals ; Cyclophosphamide/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred BALB C ; Mice ; *Intestinal Mucosa/drug effects/microbiology ; *Polysaccharides/pharmacology ; Inflammation ; *Poria/chemistry ; Wolfiporia/chemistry ; Male ; },
abstract = {OBJECTIVES: To investigate the protective effects of Poria cocos polysaccharide (PCP) against cyclophosphamide (CTX)-induced intestinal mucosal injury and its impact on gut flora and their metabolites in mice.

METHODS: Adult BALB/C mice were randomized into normal control group, CTX model group, glutamine (positive control) group, and low-, medium- and high-dose PCP treatment groups. In all but the normal control group, the mice were subjected to modeling of CTX-induced intestinal mucosal injury by intraperitoneal CTX injections for 3 days, followed by treatment with gavage of normal saline, glutamine (300 mg/kg), or PCP at 75, 150, or 300 mg/kg for 7 consecutive days. The colonic expressions of tight junction proteins (occludin and ZO-1), serum endotoxin, D-lactate, and DAO levels, intestinal permeability, colon injury, and colonic cytokine levels (IL-4, IL-22, IL-17A, and IFN-γ mRNA) were assessed. Gut microbiota, short-chain fatty acids (SCFAs; mainly acetates and propionates) and colonic GPR41 expression were analyzed using 16S rRNA sequencing, GC-MS, and Western blotting, respectively. Fecal microbiota transplantation (FMT) experiment was conducted to validate the role of gut microbes in PCP-mediated repair of intestinal injuries.

RESULTS: Compared with those in the model group, the mice treated with PCP showed significantly increased colonic occludin and ZO-1 expressions, reduced serum endotoxin, D-lactate and DAO levels, and lowered intestinal permeability with increased colonic expressions of IL-4, IL-22, IL-17A, and IFN-γ mRNA. PCP treatment obviously increased the abundance of Muribaculaceae, decreased Lactobacillus and Bacteroides, increased the contents of acetate and propionate in the colon, and upregulated colonic GPR41 expression. The results of FMT experiment confirmed the crucial role of gut microbes in PCP-mediated repair of CTX-induced intestinal injuries in mice.

CONCLUSIONS: PCP can protect against CTX-induced intestinal mucosal injury in mice possibly by modulating gut flora and SCFAs metabolism to enhance intestinal defense capacity.},
}

Animals
Cyclophosphamide/adverse effects
*Gastrointestinal Microbiome/drug effects
Mice, Inbred BALB C
Mice
*Intestinal Mucosa/drug effects/microbiology
*Polysaccharides/pharmacology
Inflammation
*Poria/chemistry
Wolfiporia/chemistry
Male

@article {pmid41539854,
year = {2026},
author = {Choi, S and Kwon, H and Kim, WK and Ko, G},
title = {Attenuation of Clostridioides difficile Infection by Clostridium hylemonae.},
journal = {Journal of microbiology and biotechnology},
volume = {36},
number = {},
pages = {e2510017},
doi = {10.4014/jmb.2510.10017},
pmid = {41539854},
issn = {1738-8872},
mesh = {*Clostridium Infections/microbiology/therapy/prevention & control ; Animals ; *Clostridium/physiology/genetics ; Gastrointestinal Microbiome ; Mice ; *Clostridioides difficile ; Disease Models, Animal ; Feces/microbiology ; Metagenomics ; },
abstract = {Clostridioides difficile infection (CDI) is a bacterial infection of the colon that can cause diarrhea and colitis. The use of antimicrobials disrupts the intestinal microbiota, weakening colonization resistance and creating an environment in which C. difficile can establish infection. It is, therefore, necessary to identify specific bacteria that are helpful for the recovery of the intestinal microbiota in individuals with CDI. Previous studies have identified several strains that showed a negative correlation with C. difficile. Among these strains, C. hylemonae DSM 15053, which possesses the bai operon similar to Clostridium scindens, was selected. To test this hypothesis, we utilized a CDI mouse model and evaluated the inhibitory effect of C. hylemonae DSM 15053. Furthermore, to gain insights into the underlying mechanisms, we performed gut microbiota analysis. Contrary to our expectations, C. hylemonae DSM 15053 did not significantly produce SBAs. Interestingly, however, microbial diversity and richness were significantly higher in the C. hylemonae DSM 15053-treated group compared with the PBS control group. In addition, we observed a higher abundance of the genera Phocaeicola, Akkermansia, and Parabacteroides in the C. hylemonae DSM 15053 group. Moreover, metagenomic and metabolomic analyses revealed that C. hylemonae DSM 15053 mitigates CDI through a mechanism distinct from that of C. scindens KCTC 5591, which primarily functions as a regulator of bile acid metabolism.},
}

*Clostridium Infections/microbiology/therapy/prevention & control
Animals
*Clostridium/physiology/genetics
Gastrointestinal Microbiome
Mice
*Clostridioides difficile
Disease Models, Animal
Feces/microbiology
Metagenomics

@article {pmid41539785,
year = {2026},
author = {Huang, F and Guo, A and Liu, S and Liu, H and Zhang, Z and Lin, T and Xiao, S and Luo, K and Kong, J and Wu, L and Yan, H},
title = {Gut microbiota-derived propionate alleviate traumatic painful neuroma through inhibiting the RIG-I-NF-κB-mediated neuroinflammation.},
journal = {Food research international (Ottawa, Ont.)},
volume = {226},
number = {},
pages = {118087},
doi = {10.1016/j.foodres.2025.118087},
pmid = {41539785},
issn = {1873-7145},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology/drug effects ; *NF-kappa B/metabolism ; Mice ; *Propionates/pharmacology/metabolism ; Fecal Microbiota Transplantation ; Male ; *DEAD Box Protein 58/metabolism ; *Neuroma/drug therapy ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Disease Models, Animal ; *Neuroinflammatory Diseases ; Sciatic Nerve/injuries ; },
abstract = {Traumatic painful neuroma (TPN) is a debilitating condition that frequently develops after peripheral nerve injury, yet its pathogenesis remains poorly elucidated. Growing evidence implicates the gut microbiota in the regulation of pain and inflammatory processes, but its specific role in TPN has not been investigated. This study examines the contribution of the gut microbiota and its metabolite propionate to TPN development via modulation of the RIG-I-NF-κB signaling pathway. In a murine model of sciatic nerve transection, we identified distinct gut microbial communities between TPN-susceptible and non-susceptible mice, characterized by a reduction in beneficial bacteria and decreased fecal propionate levels in TPN-prone mice. Depletion of gut microbiota through antibiotic treatment aggravated neuroma formation and pain-like behaviors, effects that were reversible by fecal microbiota transplantation (FMT). Administration of propionate dose-dependently ameliorated neuroinflammation, fibrotic progression, and pain responses. Mechanistic studies revealed that propionate suppressed the RIG-I-NF-κB pathway activation, downregulated pro-inflammatory cytokines, and enhanced intestinal barrier integrity. Notably, FMT from propionate-treated mice replicated these protective outcomes. Our results indicate that gut microbiota-derived propionate mitigates TPN by inhibiting RIG-I-NF-κB-driven neuroinflammation and preserving gut barrier function, underscoring the gut-brain-nerve axis as a promising target for TPN therapy.},
}

Animals
*Gastrointestinal Microbiome/physiology/drug effects
*NF-kappa B/metabolism
Mice
*Propionates/pharmacology/metabolism
Fecal Microbiota Transplantation
Male
*DEAD Box Protein 58/metabolism
*Neuroma/drug therapy
Signal Transduction/drug effects
Mice, Inbred C57BL
Disease Models, Animal
*Neuroinflammatory Diseases
Sciatic Nerve/injuries

@article {pmid41539758,
year = {2026},
author = {Zhang, T and Liu, H and Yuan, J and Xie, B},
title = {Auricularia auricula polysaccharides intervention in vivo: inhibition of endogenous malodorous gas compounds through gut regulation and enhanced liver metabolism.},
journal = {Food research international (Ottawa, Ont.)},
volume = {226},
number = {},
pages = {118122},
doi = {10.1016/j.foodres.2025.118122},
pmid = {41539758},
issn = {1873-7145},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology ; *Liver/metabolism/drug effects ; Rats ; Male ; Prebiotics/administration & dosage ; *Auricularia/chemistry ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; Feces/chemistry ; Fermentation ; Fecal Microbiota Transplantation ; *Gases/metabolism ; },
abstract = {High-fat and high-protein diets increase susceptibility to endogenous malodorous gas compounds (EMGCs), particularly in long-term enclosed environments with limited nutrients. Auricularia auricula polysaccharides (AAP) are proposed to mitigate protein residues fermentation by gut microbiota, thereby reducing EMGCs accumulation and benefiting both health and environmental quality. This study elucidated the prebiotic mechanisms of AAP via rat interventions, fecal microbiota transplantation in pseudo-sterile rats, and in vitro fermentation with AAP-derived functional components and specific bacterial strains. Results demonstrated that AAP intervention effectively reduced EMGCs levels in feces and adipose tissue induced by high-fat and high-protein diets. The degradation products of AAP, including mannitol, lactose, and lyxose, along with reshaped gut microbiota, especially the functional strain Bacteroides xylanisolvens, all exhibited independent EMGCs-inhibiting activities. Mechanistically, AAP or its degradation products enhanced hepatic CYP450 expression through bile acid-mediated enterohepatic circulation, forming a gut-liver axis for EMGCs suppression. Additionally, gut metabolites lactose and maltose promoted colonic carbohydrate absorption, hepatic Col5a3 and Col1a1 enhanced hepatic protein absorption. Upregulated gut metabolites (histidine, choline bitartrate, lactose, maltose) and hepatic genes (Abcg8, Abcb9) enriched the ABC transporter pathway, expediting hepatic EMGCs excretion. This study supports AAP as a dietary supplement to inhibit EMGCs, ensuring environmental livability and health.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Polysaccharides/pharmacology
*Liver/metabolism/drug effects
Rats
Male
Prebiotics/administration & dosage
*Auricularia/chemistry
Rats, Sprague-Dawley
Diet, High-Fat/adverse effects
Feces/chemistry
Fermentation
Fecal Microbiota Transplantation
*Gases/metabolism

@article {pmid41539609,
year = {2026},
author = {Yang, D and Ren, D and Zhang, Y and Hao, Y and Yue, Y and Li, Q and Fan, Q and Sun, C and Cui, M and Zhang, M},
title = {The Gut Microbiota Dysbiosis in Geriatric Multimorbidity: Pharmacotherapeutic Implications, Pathophysiological Mechanisms, and Precision Modulation Strategies.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103023},
doi = {10.1016/j.arr.2026.103023},
pmid = {41539609},
issn = {1872-9649},
abstract = {Aging around the world is accelerating. With that comes the intersection of geriatric multimorbidity and polypharmacy, creating a large uncertainty about the pharmacological efficacy and therapeutic consequences of medications used when multiple concurrent health issues exist. The gut microbiota coordinates the way drugs work through multiple pathways: through the way drugs are metabolised, the way they maintain immune homeostasis, and the way they regulate the epithelial barrier. For these reasons, the gut microbiota is becoming an important therapeutic target for optimizing precision medicine strategies in treating patients with geriatric multimorbidities. In this narrative review, we systematically synthesize the evidence regarding how gut dysbiosis leads to decreased efficacy of multi-drug regimens through the interplay between metabolism, immune response, and barrier function in aging patients with multimorbidities, and we evaluate targeted interventions. Furthermore, we demonstrate that current interventions (e.g., probiotics, prebiotics, fecal microbiota transplants (FMT), phage therapy, and dietary modulation) have unique benefits but are limited by inter-individual variability, safety concerns, and a lack of proven long-term efficacy. Thus, many areas of microbiota-drug interactions in older adults with multimorbidity should be explored through future research. Key areas to address are: the establishment of large, multicenter longitudinal cohorts of older adults with multimorbidity that would allow for repeated collection of microbiota profiles, medication use, and health outcomes to identify the evolving interaction between multimorbidity, microbiota, and polypharmacy; the urgent need for standardized and integrated databases of microbiome-drug interactions that harmonize data formats, provide metabolic annotations and medication identifiers in order to support reproducible cross-study validation; and the further validation and application of artificial intelligence (AI) and machine learning (ML) in clinical trials. High-dimensional data collected from cohorts and databases will enable the development of predictive algorithms to identify individual drug responses and how effective microbiota-targeted interventions will be; these algorithms must then be prospectively validated. Ultimately, these initiatives are necessary to move toward the personalized management of microbiota-drug interactions in older adults with multimorbidity, providing greater safety of polypharmacy and promoting healthy aging.},
}

@article {pmid41539110,
year = {2026},
author = {Shrivastav, K and Pandey, M and Gor, H and Nema, V},
title = {Gut virome plays an extended role with bacteriome in neurological health and disease.},
journal = {Journal of the neurological sciences},
volume = {481},
number = {},
pages = {125754},
doi = {10.1016/j.jns.2026.125754},
pmid = {41539110},
issn = {1878-5883},
abstract = {The gut-brain axis (GBA) is a complex two-way communication system that links the gastrointestinal tract and the central nervous system (CNS) through neural, immune, hormonal, and microbial pathways. The microbiota-gut-brain axis (MGBA), a more specific concept, focuses on how gut microorganisms, including bacteria, viruses, and other microbes, modulate this communication and influence neurological health. This comprehensive review examines the intricate mechanisms through which gut microorganisms modulate neural function and contribute to neurological health and disease pathogenesis. The gut microbiota, comprising bacteria, viruses, fungi, and bacteriophages, produces essential neuroactive compounds including neurotransmitters- Gamma-Aminobutyric Acid (GABA), serotonin (5-HT), dopamine (DA), short-chain fatty acids (SCFAs), and metabolites that directly influence brain physiology through vagal, hormonal, and immunological pathways. Dysbiosis of the gut microbiota has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, autism spectrum disorders, and schizophrenia. In healthy conditions, beneficial bacterial strains such as Lactobacillus species synthesize GABA and regulate mood, while SCFA-producing bacteria like Fecalibacterium prausnitzii maintain blood-brain barrier integrity and exert neuroprotective effects. Conversely, pathological states demonstrate altered microbial compositions, reduced bacterial diversity, and compromised production of beneficial metabolites. Emerging evidence highlights the previously underexplored role of the gut virome, particularly bacteriophages, in regulating bacterial populations and influencing neurodevelopment. Viral dysbiosis correlates with cognitive impairment and neurodegenerative processes through modulation of bacterial metabolism and inflammatory responses. Understanding these complex host-microbiome-virome interactions provides novel therapeutic opportunities for neurological disorders through targeted interventions including probiotics, fecal microbiota transplantation, and phage-based therapies, representing a paradigm shift toward microbiome-centered approaches in neurological medicine.},
}

@article {pmid41539104,
year = {2026},
author = {Gong, Z and Xia, Y and Jiang, Y and Zhang, Y and Xu, C and Zhao, L and Zhang, R and Cai, W and Wen, Y and Ma, J and Yang, S and Gao, S},
title = {Xin-Ji-Er-Kang alleviates heart failure induced by myocardial ischemia-reperfusion injury through reshaping gut microbiota and metabolites.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {151},
number = {},
pages = {157800},
doi = {10.1016/j.phymed.2026.157800},
pmid = {41539104},
issn = {1618-095X},
abstract = {BACKGROUND: The relationship between the gut-heart axis and heart failure has attracted growing interest, making the gut microbiota a potential target for new treatments. Previously, we have reported the beneficial effects of the traditional Chinese medicine Xin-Ji-Er-Kang (XJEK) on heart failure (HF), but the influence of the intestinal microbiota on XJEK's protection of the heart remains to be confirmed.

PURPOSE: This study investigates the role of gut microbiota in XJEK's therapeutic impact on HF and elucidates its potential mechanism.

STUDY DESIGN: MIR-induced HF model mice were established and different concentrations of XJEK were administered by gavage. The pharmacological effects of XJEK were evaluated by multiple pharmacodynamic methods. Subsequently, fecal microbiota transplantation (FMT) and antibiotic-induced microbiota inhibition were used to explore the effect of XJEK on HF. We next employed 16S rRNA sequencing combined with fecal metabolomics to investigate alterations in gut microbiota and metabolic profiles, and further investigated the effects of mono-colonization with D. piger in mice.

RESULTS: XJEK administration dose-dependently enhanced cardiac function and reduced myocardial damage in MIR-induced HF mice, as evidenced by reduced cardiomyocyte hypertrophy, diminished myocardial fibrosis, and a decline in serum levels of NT-proBNP and cTnI. FMT from XJEK-treated mice to recipient mice revealed that the therapeutic effects of XJEK on heart failure partially depend on the gut microbiota. XJEK reshaped the gut microbiota, leading to elevated abundance of probiotics Faecalibacterium, Limosilactobacillus and Bifidobacterium, while pathogenic bacteria Staphylococcus was depleted. Additionally, XJEK elevated the levels of beneficial metabolites, including deoxycholic acid and β-MCA. Notably, XJEK led to a rise in the relative abundance of D. fairfieldensis, and through the study of D. piger of the same genus, it was found that Desulfovibrio may produce beneficial effects in HF mice.

CONCLUSION: XJEK effectively improved cardiac function, mitigated myocardial injury, and suppressed the progression of heart failure. XJEK improved gut microbiota composition and related metabolism, alleviating heart failure.},
}

@article {pmid41539094,
year = {2026},
author = {Wang, L and Xiong, Z and Chen, J and Liu, J and Liu, M and Yan, X and Fang, Z},
title = {Synergistic gut microbiome-host lipid axis underlies the antihypertensive effect of Qianyang Yuyin formula.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {151},
number = {},
pages = {157804},
doi = {10.1016/j.phymed.2026.157804},
pmid = {41539094},
issn = {1618-095X},
abstract = {BACKGROUND: Prehypertension (Pre-HTN) is highly prevalent and substantially increases the risk of developing hypertension and cardiovascular disease. Gut microbiota (GM) dysbiosis and altered lipid metabolism are increasingly recognized as critical regulators of blood pressure (BP). Traditional Chinese Medicine (TCM) formulas, such as Qianyang Yuyin Granules (QYYY), offer multi-target interventions, yet their preventive mechanisms in Pre-HTN remain unclear.

PURPOSE: This study aimed to investigate the antihypertensive effects of QYYY and elucidate its underlying mechanisms in a prehypertensive rat model.

METHODS: Prehypertensive spontaneously hypertensive rats (SHRs) were treated with QYYY for four weeks. Multi-omics analyses, including metagenomics, plasma metabolomics, and transcriptomics, were conducted. Causal involvement of GM was tested using antibiotic-induced pseudo-germ-free SHRs with fecal microbiota transplantation (FMT) from QYYY-treated donors, administered alone or in combination with QYYY. Gut barrier integrity, systemic inflammation, and vascular function were evaluated by histology, immunofluorescence, transmission electron microscopy, and ELISA.

RESULTS: QYYY significantly lowered SBP and DBP, reversed GM dysbiosis, normalized the Firmicutes/Bacteroidetes ratio, and modulated differential bacteria including Frisingicoccus and Blautia. These microbial shifts correlated with restoration of lysophosphatidylethanolamines (LPEs), inversely associated with BP, revealing a GM-lipid-BP axis. FMT alone was insufficient, whereas the combination of FMT+QYYY produced the strongest antihypertensive effect, restoring intestinal barrier integrity, enhancing ZO-1 expression, and normalizing Ang-II and NO levels. Transcriptomic analyses suggested PPAR and ROS signaling pathways as potential mechanisms mediating the antihypertensive effect of QYYY.

CONCLUSION: QYYY prevents BP elevation in Pre-HTN via synergistic microbiota-dependent and independent mechanisms, offering a comprehensive strategy for early hypertension prevention.},
}

@article {pmid41539089,
year = {2026},
author = {Ou, G and Wu, J and Wang, S and Bi, W and Peng, R and Liu, P and Jiang, Y and Chen, Y and Xu, H and Deng, L and Zhao, H and Chen, X and Xu, L},
title = {Plantago asiatica L. extract alleviates hyperuricemia-associated renal injury by modulating gut microbiota to inhibit NLRP3 inflammasome activation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {151},
number = {},
pages = {157771},
doi = {10.1016/j.phymed.2026.157771},
pmid = {41539089},
issn = {1618-095X},
abstract = {BACKGROUND: Plantago asiatica L. (PTGA) is a widely used herbal medicine for the treatment of gout and hyperuricemia (HUA). Emerging evidence highlights the pivotal role of the gut microbiota in the pathogenesis of gout and HUA. However, existing research has failed to identify and verify the key mediator strains of PTGA that exert its role in lowering uric acid.

METHODS: A hyperuricemia mouse model was established by intraperitoneal co-administration of hypoxanthine (100 mg/kg) combined with potassium oxonate (50 mg/kg) daily for 10 consecutive days. Serum uric acid (sUA) levels and renal function parameters were assessed using biochemical assay kits. 16S rRNA sequencing combined with non-targeted metabolomics was employed to characterize alterations in gut microbiota and intestinal metabolites. Western blotting was performed to examine the expression of intestinal and renal uric acid transporters, intestinal tight junction proteins, and NLRP3 inflammasome-related proteins. Finally, the mediate role of gut microbiota was verified through fecal microbiota transplantation (FMT) and oral supplementation with Lachnospiraceae bacterium.

RESULTS: In the HUA model, elevated sUA levels (p < 0.01), activation of the renal NLRP3 inflammasome (p < 0.05), renal edema, and impaired renal function were accompanied by gut microbiota dysbiosis. PTGA extract markedly reduced sUA levels by approximately 70 % compared to the model group (p < 0.01), regulated uric acid transporter expression in both the intestine and kidney (p < 0.05), and reshaped gut microbiota composition. Moreover, PTGA enhanced intestinal uric acid catabolism of uric acid in the intestine. FMT and Lachnospiraceae bacterium supplementation experiments further confirmed the regulation of the gut microbiota is a key mediator of PTGA's therapeutic efficacy.

CONCLUSION: This study demonstrates that PTGA exerts hypouricemic and renoprotective effects through modulation of the gut-kidney axis by enriching Lachnospiraceae, promoting intestinal uric acid catabolism, and suppressing renal NLRP3 inflammasome activation. These findings provide novel mechanistic insights into the gut microbiota-dependent therapeutic action of herbal medicine, distinguishing this work from previous studies focused solely on direct organ-level effects.},
}

@article {pmid41538937,
year = {2026},
author = {Yan, H and Wang, C and Wang, H and Liu, J and Zhou, H and Zhong, W and Wang, X and Chen, Y and Ju, Z and Tong, H and Zhang, Y},
title = {Perfluorooctane sulfonates drives colitis via a gut microbiota-bile acid-endoplasmic reticulum stress axis in mice: Mechanistic validation and targeted interventions.},
journal = {Journal of hazardous materials},
volume = {503},
number = {},
pages = {141122},
doi = {10.1016/j.jhazmat.2026.141122},
pmid = {41538937},
issn = {1873-3336},
abstract = {Perfluorooctane sulfonate (PFOS), a widespread environmental pollutant, is implicated in systemic toxicity, yet its role in colitis remains unclear. This study aimed to investigate whether PFOS exacerbates colitis via the gut microbiota-bile acid-endoplasmic reticulum stress (ERS) axis and to explore potential interventions. Following 15-week oral PFOS exposure (0.1 or 0.3 mg/kg/d), mice developed dose-dependent colitis, featuring weight loss, colon shortening, barrier dysfunction, and elevated inflammation. High-dose PFOS disturbed bile acid homeostasis, depleting conjugated species like tauroursodeoxycholic acid (TUDCA) while accumulating deconjugated bile acids such as deoxycholic acid (DCA), thereby activating ERS pathways (PERK/eIF2α, IRE1/XBP1, ATF6). Gut microbiota analysis revealed reduced diversity, a lower Firmicutes/Bacteroidetes ratio, increased bacteria with bile salt hydrolase (BSH) activity (e.g., Lachnospira), and decreased potential bacteria (e.g., Akkermansia). Interventions with TUDCA, a BSH inhibitor, or fecal microbiota transplantation from healthy donors alleviated colitis, restored conjugated bile acids, and suppressed ERS. These findings demonstrate that PFOS triggers colitis via BSH-mediated bile acid deconjugation and ERS activation, highlighting the therapeutic potential of targeting this axis.},
}

@article {pmid41538653,
year = {2026},
author = {Zhang, H and Sun, J and Zheng, X and Yang, H and Xie, A and Ding, Y and Mei, Y and Li, J and Hu, Y and Ren, M and Liu, Y and Liang, Y},
title = {Fermented Lacticaseibacillus Paracasei Cultures Ameliorate Colitis by Modulating Microbiota-Derived Tryptophan Metabolism and Macrophage Polarization.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e13920},
doi = {10.1002/advs.202513920},
pmid = {41538653},
issn = {2198-3844},
support = {HBNYHXGG2024-10//Hubei Provincial Agricultural Science and Technology Research Project/ ; 2024AFB698//Natural Science Foundation of Hubei Province, China/ ; 2022BCE006//Key Research and Development Program of Hubei Province/ ; 2662025SKPY011//Fundamental Research Funds for the Central Universities/ ; },
abstract = {High-density solid-state fermented probiotic products, combining live bacteria with microbial and substrate-derived bioactives, offer a potential solution to address dysregulation of gut microbiota-immune homeostasis associated with inflammatory bowel disease (IBD). However, their synergistic efficacy against IBD remains elusive. Here, we discuss our high-density solid-state fermented Lacticaseibacillus paracasei culture (PYW) and its effects on dextran sulfate sodium (DSS)-induced colitis. Comparison of the effects of PYW, enriched with viable cells and bioactive metabolites-obtained via fermentation with wheat bran-with those of its thermally inactivated postbiotic (SPYW) shows superior efficacy of PYW than SPYW, with a viable bacterial load of ≥ 5 × 10[10] CFU g[-1] being indispensable. PYW effectively restores microbiota structure, restructures the gut tryptophan metabolic network, enriching indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA), which activate the aryl hydrocarbon receptor (AhR) signaling pathway, suppress pro-inflammatory mediators, and strengthen mucosal barriers. Antibiotic depletion abolishes the effects of PYW, while fecal microbiota transplantation from PYW-treated donors and exogenous ILA/IAA supplementation replicate its anti-colitic benefits. These findings suggest that PYW alleviates colitis via microbiota-dependent enrichment of ILA/IAA and subsequent AhR pathway activation, highlighting its potential as a probiotic therapeutic targeting the microbiota-metabolism-immunity regulatory axis in IBD.},
}

@article {pmid41536244,
year = {2026},
author = {Girdhar, K and Dedrick, S and Rhodes, L and Kim, D and Powis, A and Mahon, C and Chapdelaine, H and Obaid, L and McNamara, M and Altindis, E},
title = {Diet, gut microbiome, and type 1 diabetes: from risk to translational opportunity.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2614039},
doi = {10.1080/19490976.2026.2614039},
pmid = {41536244},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 1/microbiology/therapy/etiology/immunology ; Animals ; *Diet ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; Fecal Microbiota Transplantation ; },
abstract = {The incidence of type 1 diabetes (T1D) has risen sharply in recent decades, implicating the role of environmental factors in disease pathogenesis. Diet, a primary driver of gut microbiome development and composition, along with other environmental exposures, has emerged as a potential modulator of T1D risk and progression. While nutrients, such as certain vitamins, may exert protective effects, the roles of other dietary factors (e.g., early exposure to dietary antigens) remain unclear. Importantly, diet shapes the gut microbiome, which produces immunomodulatory metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), and others that directly influence immune responses. This review presents evidence on how specific dietary factors, including macronutrients (fats, carbohydrates, proteins, such as gluten and milk proteins), fibers, and breastfeeding, affect the gut microbiome and T1D. We also discuss the effects of microbiome-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, on T1D and their potential as future therapeutic strategies. Although animal studies provide compelling mechanistic insights, the results from human trials remain inconsistent, underscoring the urgent need for longitudinal and interventional studies to establish causality. Understanding the complex interplay between diet, the gut microbiome, and immune homeostasis is essential for developing personalized strategies to prevent and treat T1D and delay-related complications.},
}

Humans
*Gastrointestinal Microbiome
*Diabetes Mellitus, Type 1/microbiology/therapy/etiology/immunology
Animals
*Diet
Prebiotics/administration & dosage
Probiotics/administration & dosage
Fecal Microbiota Transplantation

@article {pmid41535719,
year = {2026},
author = {Almonte, AA and Thomas, S and Iebba, V and Kroemer, G and Derosa, L and Zitvogel, L},
title = {Gut dysbiosis in oncology: a risk factor for immunoresistance.},
journal = {Cell research},
volume = {},
number = {},
pages = {},
pmid = {41535719},
issn = {1748-7838},
support = {INCA_16698//CNIB (INCA)/ ; 955575//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; },
abstract = {The gut microbiome is recognized as a determinant of response to immune checkpoint inhibitor (ICI) therapies in cancer. However, the clinical translation of microbiome science has been hampered by inconsistent definitions of dysbiosis, inadequate biomarker frameworks, and limited mechanistic understanding. In this review, we synthesize the current state of knowledge on how gut microbial composition and function influence ICI efficacy, highlighting both correlative and causal evidence. We discuss computational approaches based on α-diversity or taxonomic abundance and argue for more functionally and clinically informative models, such as the topological score (TOPOSCORE) and other dysbiosis indices derived from machine learning. Using retrospective analyses of metagenomic datasets from thousands of patients and healthy controls, we examine microbial patterns that distinguish responders from non-responders. We also explore how dysbiosis perturbs immunoregulatory pathways, including bile acid metabolism, gut permeability, and mucosal immunomodulation. Finally, we assess emerging therapeutic strategies aimed at correcting microbiome dysfunction - including dietary modification, bacterial consortia, and fecal microbiota transplantation - and describe how they are being deployed in multiple clinical trials. We conclude with a brief discussion of the ONCOBIOME initiative, which works with international partners to incorporate microbiome science into oncology workflows. By refining our understanding of gut-immune interactions and translating it into action, microbiome-informed oncology may unlock new therapeutic potential for patients previously resistant to immunotherapy.},
}

@article {pmid41535683,
year = {2026},
author = {Chen, S and Yuan, Y and Wang, Y and Peng, Y and Tun, HM and Jiang, Z and Miao, Y and Lee, S and Yin, X and Shen, X and DeLeon, O and Chang, EB and Chan, FKL and Sun, Y and Ng, SC and Su, Q},
title = {Identification of antimicrobial peptides from ancient gut microbiomes.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68495-0},
pmid = {41535683},
issn = {2041-1723},
support = {2025 Youth Science and Technology Talent Development Program//China Association for Science and Technology (China Association for Science & Technology)/ ; },
abstract = {Fecal coprolites preserve ancient microbiomes and are a potential source of extinct but highly efficacious antimicrobial peptides (AMPs). Here, we develop AMPLiT (AMP Lightweight Identification Tool), an efficient tool deployable to portable hardware for AMP screening in metagenomic datasets. AMPLiT demonstrates AUPRC performances of 0.9486 ± 0.0003 and reasonable overall training time of 3200 ± 53 s. By computationally utilizing AMPLiT, we analyze seven ancient human coprolite metagenomes, identifying 160 AMP candidates. Of 40 representative peptides synthesized, 36 (90%) peptides demonstrate measurable antimicrobial activity at 100 μM or less in vitro. Strikingly, approximately two-thirds of these peptides are sourced from Segatella copri, a dominant ancient gut commensal that is conspicuously underrepresented in modern populations, particularly those with Westernized lifestyles. Representative S. copri-derived AMPs exhibit disruptions against membranes of pathogenic bacteria, coupled with low cytotoxicity and hemolytic risk. In vivo, lead peptides demonstrate potent antibacterial and wound-healing efficacy comparable to traditional antibiotics, especially in combating gram-positive pathogens. Our findings highlight the ancient gut microbiomes as sources of novel AMPs, offering valuable insights into the historical role of S. copri in human health and its decline in contemporary populations.},
}

@article {pmid41535300,
year = {2026},
author = {Wong, OWH and Xu, Z and Chan, SSM and Mo, FYM and Shea, CKS and Su, Q and Wan, MYT and Cheung, CP and Ching, JYL and Tang, W and Tun, HM and Chan, FKL and Ng, SC},
title = {A novel synbiotic (SCM06) for anxiety and sensory hyperresponsiveness in children with autism spectrum disorder: an open-label pilot study.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-025-00902-8},
pmid = {41535300},
issn = {2055-5008},
support = {NCI202346//New Cornerstone Science Foundation/ ; },
abstract = {Anxiety and sensory hyperresponsiveness are common in children with autism spectrum disorder (ASD), but effective treatments are lacking. Targeting the microbiota-gut-brain axis is a promising strategy. This open-label pilot study evaluated SCM06, a novel synbiotic designed to target anxiety and sensory hyperresponsiveness, in 30 children with ASD (mean age 8.2 years, 22 males). We assessed symptom improvement, compliance, and safety, and collected stool samples for metagenomics and metabolomic analysis over 12 weeks. SCM06 was safe and well-tolerated, and significant improvements were observed in anxiety, sensory hyperresponsiveness, and abdominal pain. Following SCM06 treatment, increase in Bifidobacterium pseudocatenulatum was associated with improved functional abdominal pain (p = 0.0011, p_adj = 0.054), while the abundances of valeric acid and butyric acid increased (p_adj = 0.004 and p_adj = 0.072). Key microbial species, Coprococcus comes and Veillonella dispar, were candidate mediators of symptom improvements. Further randomised controlled trials are warranted to confirm its clinical efficacy.},
}

@article {pmid41447757,
year = {2026},
author = {Mandala, A and Undi, RB and Janssen, RC and Sugino, KY and Zhao, W and Nelson, BN and Teague, AM and Patil, NY and Zemsky Berry, K and Varshney, R and Bergman, BC and Rudolph, MC and Joshi, AD and Rajala, RVS and Jonscher, KR and Friedman, JE},
title = {Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.},
journal = {EBioMedicine},
volume = {123},
number = {},
pages = {106098},
pmid = {41447757},
issn = {2352-3964},
mesh = {Animals ; Female ; *Indoles/administration & dosage/pharmacology ; Mice ; Humans ; Pregnancy ; Male ; Gastrointestinal Microbiome/drug effects ; *Liver/metabolism/pathology/drug effects ; *Dietary Supplements ; *Fatty Liver/prevention & control/etiology/metabolism/pathology ; Disease Models, Animal ; Prenatal Exposure Delayed Effects ; Receptors, Aryl Hydrocarbon/metabolism ; Diet, Western/adverse effects ; Maternal Exposure ; Ceramides/metabolism ; Fecal Microbiota Transplantation ; Hepatic Stellate Cells/metabolism/drug effects ; Indoleacetic Acids ; },
abstract = {BACKGROUND: Disruptions in early-life gut microbiota and metabolites associated with maternal Western-style diet (WD) during critical windows of development are linked to metabolic and inflammatory diseases in offspring, including metabolic dysfunction-associated steatotic liver disease (MASLD) in later life. These disturbances can alter microbial metabolite production, such as tryptophan derivatives, which are crucial for immune and metabolic regulation. However, the specific effects of maternal supplementation with tryptophan metabolites on offspring gut microbiome maturation and MASLD risk remain unexplored.

METHODS: WD-fed mouse dams were supplemented with microbial metabolites indole (Ind) or indole-3-acetic acid (I3A) during gestation and lactation; male offspring were weaned to chow diet for 9 weeks, followed by a 4-week WD challenge. Fecal microbiota transfer (FMT) was performed from offspring to naïve recipients, followed by a 4-week WD challenge. Human LX-2 stellate cells were used to study mechanisms for indole and very long-chain (VLC) ceramide effects on TGF-β-induced fibrosis.

FINDINGS: Maternal supplementation with Ind or I3A had long-term protective effects in adult WD-challenged offspring against excess weight gain, steatosis, stellate cell activation, and fibrosis. Perinatal exposure to Ind or I3A activated offspring aryl hydrocarbon receptor (AHR) signalling in gut and liver, which trans-repressed known and new target genes, including ceramidases Asah2 and Acer3, leading to increased VLC ceramides. FMT from offspring with perinatal exposure to Ind protected recipients from WD-induced fibrogenesis and increased beneficial VLC ceramides in recipient livers. In vitro, LX-2 stellate cells cultured with Ind or VLC ceramides demonstrated an anti-fibrotic effect, which was abolished by AHR inhibition.

INTERPRETATION: Maternal indole supplementation, through sustained activation of AHR in offspring gut and liver and an increase in hepatic VLC ceramides, prevents diet-induced MASLD and fibrosis in offspring, offering a novel therapeutic pathway for prevention of paediatric MASLD.

FUNDING: See Acknowledgements.},
}

Animals
Female
*Indoles/administration & dosage/pharmacology
Mice
Humans
Pregnancy
Male
Gastrointestinal Microbiome/drug effects
*Liver/metabolism/pathology/drug effects
*Dietary Supplements
*Fatty Liver/prevention & control/etiology/metabolism/pathology
Disease Models, Animal
Prenatal Exposure Delayed Effects
Receptors, Aryl Hydrocarbon/metabolism
Diet, Western/adverse effects
Maternal Exposure
Ceramides/metabolism
Fecal Microbiota Transplantation
Hepatic Stellate Cells/metabolism/drug effects
Indoleacetic Acids

@article {pmid41392089,
year = {2025},
author = {Wilson, BC and Tweedie-Cullen, RY and Albert, BB and Derraik, JGB and Ho, D and Depczynski, M and Creagh, C and Edwards, T and Gali, S and Thabrew, H and Cutfield, WS and O'Sullivan, JM},
title = {Encapsulated faecal microbiota transfer in young women with anorexia nervosa: an open-label feasibility pilot trial.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {571},
pmid = {41392089},
issn = {2041-1723},
mesh = {Humans ; *Anorexia Nervosa/therapy/microbiology ; Female ; Pilot Projects ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome/physiology ; Feasibility Studies ; Young Adult ; Adult ; Adolescent ; Treatment Outcome ; Feces/microbiology ; },
abstract = {Perturbations of the gut microbiome have been associated with anorexia nervosa (AN) suggesting microbiome-modulation treatments, like faecal microbiota transfer (FMT), may offer therapeutic benefits. This open-label feasibility pilot trial evaluated the tolerability and microbiological impact of encapsulated, multi-donor FMT in 18 young women with AN (Registration: ACTRN12621001504808). Participants completed clinical and microbiome assessments at enrolment (3 weeks pre-treatment), baseline, and 3, 6, and 12 weeks post-treatment. Fifteen participants completed FMT, and 11 completed the final follow-up. The primary outcome was the change in gut microbiome composition from baseline to 3 weeks compared with natural variation between enrolment and baseline. FMT produced a significantly greater shift post-treatment (mean ± SD Bray-Curtis dissimilarity 0.36 ± 0.11; p = 0.0007), with participants gaining 38 ± 16 new species. Donor-derived strains comprised 41 ± 12% of the microbiome at 3 weeks, with engraftment persisting at 6 and 12 weeks. FMT was generally well tolerated; adverse events were mostly mild to moderate and overlapped with typical AN symptomatology. Monitoring of clinical outcomes supported the safety profile and suggested potential improvements in anxiety and metabolic parameters; however, the small sample and absence of a control arm preclude safety and efficacy inference. Overall, these findings warrant further investigation through randomised controlled trials in AN.},
}

Humans
*Anorexia Nervosa/therapy/microbiology
Female
Pilot Projects
*Fecal Microbiota Transplantation/methods/adverse effects
*Gastrointestinal Microbiome/physiology
Feasibility Studies
Young Adult
Adult
Adolescent
Treatment Outcome
Feces/microbiology

@article {pmid41535289,
year = {2026},
author = {Panah, FM and Støving, RK and Sjögren, M and Micali, N and Maschek, S and Reis, KD and Mirsepasi-Lauridsen, HC and Petersen, AM and Nielsen, DS and Helms, M and Rasmussen, MA and Barfod, KK},
title = {Impact of a single fecal microbiome transplantation in adult women with anorexia nervosa: an open-label feasibility pilot trial.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68455-8},
pmid = {41535289},
issn = {2041-1723},
support = {R370-2021-863//Lundbeckfonden (Lundbeck Foundation)/ ; },
abstract = {Anorexia nervosa (AN) is a severe mental disorder characterized by restrictive eating and disturbance in the way one's body weight or shape is experienced, often accompanied by depression and anxiety. Current evidence-based treatments for AN have limited efficacy, with less than half of the patients achieving full recovery in long-term follow-up studies. Recent findings have identified gut microbiota (GM) dysbiosis as a potential contributor to AN pathology through the gut-brain axis. This open-label, non-randomized, feasibility trial (Clinicaltrials.gov Identifier: NCT05834010) evaluated the feasibility of utilizing fecal microbiota transplantation (FMT) to modify the GM and GM-associated signaling in females with AN and to examine biological effects following a single FMT procedure. Adult female participants diagnosed with AN were recruited. FMT was administered either orally via capsules or as rectal enema. Stool and blood samples were collected pre- and one week post-FMT to assess GM composition, hormonal changes, and biomarkers. Primary endpoints: Feasibility of FMT in individuals with AN and preferred route of FMT. Secondary endpoints: A single FMT treatment can alter GM composition in individuals with AN short term and relevant gut brain signaling in serum. 18/22 participants (81%) completed FMT and sampling and 19/22 participants chose oral capsules, with no serious adverse effects reported. GM analysis showed significant shifts toward donor composition 1-week post-FMT, with improved stool consistency. No significant changes were observed in psychopathology measures or appetite-related biomarkers. Oral FMT is a feasible intervention for adult women with AN, leading to changes in GM profile. Future studies should focus on placebo-controlled trials to assess the efficacy of repeated oral treatments and explore long-term effects on GM, appetite, body weight, sex hormones, disorder-specific symptoms, and overall well-being.},
}

@article {pmid41532069,
year = {2026},
author = {Mu, S and Chang, M and Shen, Y and Wu, X and Han, Y and Xiang, H and Luo, Y and Chen, Y and Zheng, H and Song, Z and Tong, C},
title = {Gut microbiota metabolite butyric acid alleviated Klebsiella Pneumoniae induced lung injury by regulating CX3CR1[+]NK via PI3K/AKT pathway.},
journal = {Burns & trauma},
volume = {14},
number = {},
pages = {tkaf069},
doi = {10.1093/burnst/tkaf069},
pmid = {41532069},
issn = {2321-3868},
abstract = {BACKGROUND: The expression of CX3CR1 is regulated by the gut microbiota and is correlated with the prognosis of sepsis in patients. However, the underlying mechanism has remained uncertain. This study aims to explore the role of gut microbiota components in regulating CX3CR1 expression and its impact on pneumonia-induced lung injury during sepsis.

METHODS: Mice were fed a mixture of antibiotics to establish a pseudogerm-free mouse model and then infected with Klebsiella pneumoniae. Fecal microbiota transplantation (FMT) was performed on microbiota-depleted mice, and 16S rRNA gene sequencing and targeted metabolomics were used to identify the key metabolites. Flow cytometry was employed to analyze the phenotypes of natural killer (NK) cells. Butyric acid was added as a supplement for rescue. Next, NK92 cells were pretreated with butyric acid to explore the potential signaling pathways involved.

RESULTS: In the animal study, we revealed that the expression of CX3CR1 on NK cells depended on the intestinal microbiota and its metabolites, which were related to the survival rates of gut microbiota-depleted mice after K. pneumoniae infection. FMT increased the percentage of CX3CR1[+] NK cells in the lungs of these mice, restored the disordered microbiota and metabolites, and alleviated the lung injury induced by infection. Among the metabolites, butyric acid was identified as the key metabolite and was shown to increase the proportion of CX3CR1[+] NK cells and interferon (IFN)-γ secretion, reduce bacterial loads, increase lung tissue damage, and increase survival rates. In vitro, butyric acid activated the PI3K/AKT pathway in NK92 cells, promoted CX3CR1 expression, and enhanced NK cell activity and migration ability.

CONCLUSIONS: We concluded that butyric acid alleviated K. pneumoniae-induced lung injury by regulating CX3CR1[+] NK cells via the PI3K/AKT pathway.},
}

@article {pmid41530748,
year = {2026},
author = {Zhang, Y and Sun, C and Wang, Y and Zhang, H and Fan, Y and Zhao, H and Li, P},
title = {Targeting gut-liver-kidney axis: microbiota-derived metabolites and therapeutic implications.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-025-02625-x},
pmid = {41530748},
issn = {1478-811X},
support = {82174296//National Natural Science Foundation of China/ ; },
abstract = {The gut-liver-kidney axis has emerged as a central regulatory network orchestrating metabolic, immune, and inflammatory homeostasis across organ systems. At its core lies the dynamic interplay between gut microbiota and host metabolism. Dysbiosis and impaired intestinal barrier integrity facilitate the systemic translocation of microbial metabolites-such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine-N-oxide (TMAO), and tryptophan derivatives-which profoundly influence hepatic lipid metabolism, renal immune responses, and overall metabolic balance. This review examines the molecular mechanisms through which gut-derived metabolites contribute to liver and kidney pathology, emphasizing inter-organ signaling and the pathological cascade of the "leaky gut-hepatic injury-renal dysfunction" loop. We critically evaluate emerging therapeutic strategies targeting this axis, including probiotic supplementation, fecal microbiota transplantation (FMT), dietary modulation (low-protein, high-fiber regimens), and pharmacological detoxification (e.g., AST‑120, molecular adsorbent recirculating systems [MARS]). Finally, we propose a conceptual "diet-microbiota-drug" triad to guide precision interventions, and discuss current challenges such as interindividual variability, the lack of standardized assessment tools, and the need for integrative multi‑omics and clinical validation. A deeper mechanistic understanding of gut-organ crosstalk may pave the way for innovative therapies to restore systemic metabolic homeostasis.},
}

@article {pmid41530607,
year = {2026},
author = {Miller, CB and Bader, GA and Kay, CL},
title = {Fecal Microbiota Transplantation in 2025: Two Steps Forward, One Step Back.},
journal = {Current gastroenterology reports},
volume = {28},
number = {1},
pages = {5},
pmid = {41530607},
issn = {1534-312X},
mesh = {*Fecal Microbiota Transplantation/trends/methods ; Humans ; *Irritable Bowel Syndrome/therapy ; *Clostridium Infections/therapy ; *Inflammatory Bowel Diseases/therapy ; },
abstract = {PURPOSE OF REVIEW: This review summarizes the history and current landscape of fecal microbiota transplantation (FMT), with an emphasis on use of the therapy for Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). We clarify indications, evidence, and current recommendations for FMT-highlighting major advances and minor setbacks that have led to the state of FMT in 2025.

RECENT FINDINGS: After decades of steady progress, the U.S. Food and Drug Administration (FDA) approved the first FMT-based therapies: fecal microbiota, live-jslm and fecal microbiota spores, live-brpk-in 2022 and 2023, respectively. The 2024 American Gastroenterological Association (AGA) Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases made specific recommendations for conventional FMT and these FDA-approved therapies for multiple CDI presentations, as well as for IBD and IBS. Conventional FMT remains an option for CDI; however, OpenBiome's halt of shipped, frozen FMT preparations on December 31, 2024, has made access more challenging in 2025. Although first reported almost seventy years ago, extensive efforts over the last two decades have placed FMT in routine algorithms for many patients with CDI. While understanding of the intestinal microbiome's role in other gastrointestinal conditions is expanding, and FMT may modulate these pathways, additional evidence is needed before FMT becomes routine outside CDI.},
}

*Fecal Microbiota Transplantation/trends/methods
Humans
*Irritable Bowel Syndrome/therapy
*Clostridium Infections/therapy
*Inflammatory Bowel Diseases/therapy

@article {pmid41530574,
year = {2026},
author = {Deng, YH and Liu, Q and Luo, XQ},
title = {The gut-kidney axis in pediatric acute kidney injury: a review of pathophysiological mechanisms and therapeutic frontiers.},
journal = {Pediatric nephrology (Berlin, Germany)},
volume = {},
number = {},
pages = {},
pmid = {41530574},
issn = {1432-198X},
support = {2024JJ6595//Natural Science Foundation of Hunan Province/ ; },
abstract = {Acute kidney injury (AKI) is a frequent and severe condition in hospitalized children, leading to significant morbidity, mortality, and long-term risk of chronic kidney disease. This review explores the gut-kidney axis, a concept describing the bidirectional relationship between the gut microbiome and kidney function, as a critical driver of pediatric AKI. In critically ill children, interventions such as broad-spectrum antibiotics and necessary nutritional support strategies (e.g., parenteral nutrition or fasting) can cause profound gut microbial imbalance (dysbiosis). This dysbiosis initiates a deleterious feedback loop, exacerbating kidney injury. Key mechanisms include the disruption of the intestinal barrier (leaky gut), which allows bacterial endotoxins to enter the bloodstream, triggering renal inflammation via Toll-like receptor 4 signaling. Concurrently, the dysbiotic gut increases production of directly nephrotoxic gut-derived uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, while failing to produce protective anti-inflammatory metabolites like short-chain fatty acids. While therapies targeting the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, are theoretically promising, their clinical use in pediatric AKI is unsupported by evidence and carries substantial risks, particularly iatrogenic infection. A significant knowledge gap exists due to a relative lack of pediatric-specific clinical research. The conclusion emphasizes an urgent need for longitudinal, multi-omics studies in children to understand this axis, identify functional biomarkers, and develop safe, targeted therapies to improve outcomes.},
}

@article {pmid41529466,
year = {2026},
author = {Wang, Z and Yu, Y and Shao, W and Zhao, Y and Li, Z and Han, J and Wen, J and Meng, Y and Lin, Y and Wang, S},
title = {Puerarin ameliorates alcoholic liver disease by regulating intestinal flora and MAPK/Nrf2 signalling pathways.},
journal = {Ecotoxicology and environmental safety},
volume = {309},
number = {},
pages = {119699},
doi = {10.1016/j.ecoenv.2026.119699},
pmid = {41529466},
issn = {1090-2414},
abstract = {Puerarin is a natural flavonoid glycoside extracted from the traditional Chinese medicine Puerariae Lobatae Radix or Pueraria lobata (Willd), known for its hepatoprotective properties. While prior studies indicate that PR can mitigate ALD, the underlying mechanisms by which PR exerts its anti-ALD effects via intestinal flora remain poorly understood. This study aimed to investigate the metabolic differences of PR in normal and ALD model rats were analyzed using UHPLC-HRMS. Further validation of PR metabolic products in vivo through in vitro fecal fermentation. Additionally, the relationship between the anti-ALD properties of PR and intestinal flora was explored using 16S rRNA sequencing technology, with confirmation obtained from fecal microbiota transplantation (FMT) experiments and functional strain experiments. Finally, through non-targeted metabolomics and liver transcriptomics combined with in vitro cell pharmacological studies, the mechanism of action of PR and its in vitro fermentation metabolites against ALD was explored. In the PR metabolic test, 20 metabolites were identified in the serum, urine, and feces of normal and ALD model rats, primarily associated with reactions including deglycosylation, hydrogenation, aldehyde esterification, hydroxylation, and methylation. 6 metabolites were verified in vitro transformation system. Subsequently, we used FMT experiments and 16S rRNA sequencing to find that intestinal flora imbalance can lead to liver disease and PR can improve liver disease by regulating intestinal flora. Based on multi-omics analysis and in vitro pharmacological activity analysis, PR and its in vitro fermented metabolites inhibit MAPK and Nrf2 pathways, further reducing inflammation and oxidative stress. The results of this study show that PR can improve ALD, with its mechanism of action potentially involving regulation of the intestinal flora, suppression of inflammatory responses, and inhibition of oxidative stress.},
}

@article {pmid41527151,
year = {2026},
author = {Li, JY and Huang, HB and Shi, CW and Pan, TX and Li, MH and Wang, N and Shan, JJ and Jiang, YL and Yang, WT and Cao, X and Wang, JZ and Guan, JY and Yu, SY and Wang, CF and Yang, GL},
title = {Increased caecal Intestinimonas abundance inhibits E. tenella gametogenesis via EtGFAT regulation and alleviates infection through immunity.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02302-8},
pmid = {41527151},
issn = {2049-2618},
support = {32072888, U21A20261, 32202819//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Chicken coccidiosis caused by Eimeria tenella (E. tenella) poses a major threat to global poultry production, with its tropism for the caecal microenvironment and dynamic interactions with the resident microbiota remaining incompletely understood. The caecal microbiota plays a critical role in host‒parasite interplay, yet the mechanisms through which microbial homeostasis influences E. tenella development and host resistance remain elusive. This study aimed to elucidate the causal relationship between caecal dysbiosis and E. tenella pathogenesis, with a focus on identifying microbiota-derived regulators of parasite development and host immunity.

RESULTS: Antibiotic-induced caecal dysbiosis (ABX) significantly impaired E. tenella macrogametogenesis, demonstrating microbiota-dependent regulation of parasitic development. Faecal microbiota transplantation (FMT) validated this causal link, revealing that microbial reconstitution restored parasite maturation. Notably, Intestinimonas spp. were identified as key inhibitors of E. tenella development through transcriptional regulation of the EtGFAT gene (Eimeria tenella glucosamine: fructose-6-phosphate aminotransferase), a critical mediator of macrogamete formation. Furthermore, the transplantation of Intestinimonas butyriciproducens (I. butyriciproducens) attenuated clinical manifestations of infection while increasing IFN-γ secretion from CD8[+] T lymphocytes, thereby enhancing host resistance to E. tenella.

CONCLUSIONS: This study revealed that caecal microbiota homeostasis is indispensable for E. tenella developmental progression and highlights Intestinimonas as a pivotal microbial regulator of parasite biology. The dual role of I. butyriciproducens in suppressing parasitic virulence and potentiating adaptive immune responses underscores the therapeutic potential of microbiota-targeted strategies. These findings provide a foundation for the development of novel anticoccidial interventions through targeted manipulation of caecal microbial communities. Video Abstract.},
}

@article {pmid41461024,
year = {2026},
author = {Ng, DZW and Koh, M and Low, A and Liu, L and Jumat, NHB and Zhang, Z and Koh, XQ and Zhu, M and Muthiah, M and Dan, YY and Lee, JWJ and Chan, ECY},
title = {Robust Workflow for Multiclass Host-Gut Microbial Cometabolite Quantitation in Human Stool via 3-Nitrophenylhydrazine Derivatization and LC-MS/MS: A Validated Analytical Platform for Translational Studies.},
journal = {Analytical chemistry},
volume = {98},
number = {1},
pages = {555-570},
doi = {10.1021/acs.analchem.5c05360},
pmid = {41461024},
issn = {1520-6882},
mesh = {Humans ; Tandem Mass Spectrometry/methods ; *Gastrointestinal Microbiome ; *Feces/chemistry/microbiology ; Chromatography, Liquid ; *Phenylhydrazines/chemistry ; *Fatty Acids, Volatile/analysis/metabolism ; *Bile Acids and Salts/analysis/metabolism ; Workflow ; Amino Acids, Branched-Chain/analysis/metabolism ; Tryptophan/analysis/metabolism ; Liquid Chromatography-Mass Spectrometry ; },
abstract = {Host-gut microbial co-metabolites, including short-chain fatty acids (SCFA), bile acids (BA), tryptophan metabolites, and branched-chain amino acids (BCAA), have key immune-metabolic functions affecting human health. Dysbiosis-induced alterations in their levels are implicated in the pathogenesis of diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). However, simultaneous quantitation of these chemically diverse analytes in stool remains analytically challenging due to their diverse physicochemical properties and wide concentration ranges. Here, we developed and rigorously validated a derivatization and targeted liquid chromatography tandem mass spectrometry workflow for the simultaneous quantitation of host-gut microbial cometabolites in human stool. A 3-nitrophenylhydrazine derivatization protocol was optimized by systematically adjusting reagent concentrations and introducing postreaction quenching to suppress in-line acetic acid derivatization. Chromatographic separation was enhanced by using a novel dual-additive mobile-phase strategy (formic acid and ammonium acetate in aqueous and organic phase, respectively) coupled to a mixed-mode C18-anion-exchange stationary phase, enabling improved resolution and sensitivity across chemically diverse metabolite classes. Our optimized analytical method achieved accurate, sensitive, and efficient quantitation of 38 metabolites (15 SCFA, 16 BA, 4 tryptophan metabolites, 3 BCAA) within 23 min, demonstrating excellent linearity (r[2] > 0.99) and precision (CV < 15%), with short- (autosampler, 4 °C) and long-term (freezer, -20 °C) stability. Comparative analysis of healthy controls and MASLD stools revealed distinct metabolic signatures, including reduced SCFA and C6-oxidized BA, and elevated conjugated and secondary BA derivatives in MASLD. Our study establishes an analytically rigorous platform for multiclass host-gut cometabolite quantitation in stool, with demonstrated utility for translational research into gut-liver axis disorders.},
}

Humans
Tandem Mass Spectrometry/methods
*Gastrointestinal Microbiome
*Feces/chemistry/microbiology
Chromatography, Liquid
*Phenylhydrazines/chemistry
*Fatty Acids, Volatile/analysis/metabolism
*Bile Acids and Salts/analysis/metabolism
Workflow
Amino Acids, Branched-Chain/analysis/metabolism
Tryptophan/analysis/metabolism
Liquid Chromatography-Mass Spectrometry

@article {pmid41527019,
year = {2026},
author = {Zhong, J and Zhu, B and Zou, Z and Li, Y and Feng, Y and Wu, K and Hou, X},
title = {Gut microbiota mediates the beneficial effects of exercise on autism-like behaviors.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-025-04632-x},
pmid = {41527019},
issn = {1471-2180},
support = {no. 2025A04J4356//the Guangzhou Municipal Science and Technology Bureau, Basic Research Program/ ; no. 2023B0303020001//the Key-Area Research and Development Program of Guangdong Province/ ; no. 2021ZDJS021//the Provincial Significant Scientific Research Projects for General Universities in Guangdong Province/ ; },
abstract = {BACKGROUND: The gut-brain axis plays a critical role in autism spectrum disorder (ASD), but the mechanisms through which exercise modulates gut microbiota, short-chain fatty acids (SCFAs), and central neurotransmitters to ameliorate ASD-like behaviors remain unclear. This study aimed to investigate the effects of exercise on ASD-like behaviors, gut microbiota, and metabolism in a valproic acid (VPA)-induced ASD rat model and to validate these findings via fecal microbiota transplantation (FMT).

METHODS: ASD rat models were established through prenatal exposure to VPA and divided into four groups: exercise (E_ASD), non-exercise (ASD), FMT, and sham FMT (sFMT). The E_ASD group underwent 6 weeks of voluntary wheel running, while the FMT group received fecal microbiota from the E_ASD group for 4 weeks. Behavioral assessments were conducted to evaluate cognitive and social functions. Fecal microbiota composition was analyzed via 16S rRNA sequencing, while SCFAs and neurotransmitters were measured using gas and liquid chromatography-mass spectrometry.

RESULTS: Six weeks of voluntary exercise significantly alleviated ASD-like behaviors, particularly improving social interactions. Exercise also altered gut microbiota composition, increasing Limosilactobacillus and Lactobacillus while decreasing Allobaculum. Additionally, SCFAs and neurotransmitter levels in the prefrontal cortex were modulated. Notably, FMT from the exercise group replicated these behavioral and metabolic improvements in ASD rats. Exercise improves ASD-like behaviors by modulating gut microbiota, SCFAs, and neurotransmitter levels, and FMT offers further validation of these effects.

CONCLUSION: These findings highlight exercise and FMT as promising strategies for alleviating ASD-related symptoms through gut-brain axis modulation.},
}

@article {pmid41526816,
year = {2026},
author = {Yang, Y and Wang, Y and Li, J and Gao, Y and Wu, Z and Tan, X and Feng, S and Cheng, W and Zhang, H and Gan, Q and Wei, H and Li, Q},
title = {Fecal microbiota transplantation from healthy piglets ameliorates intestinal inflammation in mice by modulating recipient metabolism.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-025-04590-4},
pmid = {41526816},
issn = {1471-2180},
support = {2025J01556//Fujian Provincial Natural Science Foundation of China/ ; },
}

@article {pmid41525948,
year = {2026},
author = {Valia, D and Karama, I and Ingelbeen, B and Garba, Z and Kleef, EV and Lompo, P and Tiendrebeogo, EW and Kaboré, B and Kiemdé, F and Yougbare, S and Tiendrebeogo, AL and Van Puyvelde, S and Prizzon, A and Vandenbroucke, AT and Argudín, MA and Kabamba, BM and Jacobs, J and Tinto, H and van der Sande, MAB and Robert, A and Rodriguez-Villalobos, H},
title = {Faecal colonisation with extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in rural Burkina Faso.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2026.01.001},
pmid = {41525948},
issn = {1469-0691},
abstract = {OBJECTIVES: The burden of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) is rising globally and often linked to community-acquisition in low-resource settings. In sub-Saharan Africa (sSA), AMR occurrence in rural areas remains under-studied despite anticipated higher risks. We investigated the epidemiology and genetic characteristics of ESBL-E in rural Burkina Faso.

METHODS: In a community-based cross-sectional survey (May 2021-May 2022), participants were randomly selected in two health catchment areas and through face-to-face interviews, field workers collected data on hygiene, animal presence, household characteristics, and healthcare use. Stool samples were also collected for ESBL-E screening. Prevalence of ESBL-producing E. coli (ESBL-EC) and K. pneumoniae (ESBL-KP) was estimated, and associated factors assessed. Based on resistance profiles and PCR screening, selected isolates underwent whole-genome sequencing.

RESULTS: Among 1,482 participants, ESBL-E prevalence was 61.3% (58.8-63.7%): ESBL-EC 53.0% (50.5-55.5%) and ESBL-KP 22.3% (20.3-24.5%). Colonisation was more common in the rainy than dry season (70.2% vs 53.6%, p<0.001) and among individuals not washing hands with soap before meals (62.5% vs 49.0%, p<0.001). Ciprofloxacin-resistance exceeded 65% in both species. The predominant ESBL-gene was blaCTX-M-15 (47.3% in ESBL-EC, 19.9% in ESBL-KP), with one ESBL-EC isolate carrying blaNDM-5. IncF plasmids predominated, and plasmid-mediated quinolone-resistance genes (qnr, aac(6')-ib-cr, oqxAB) were frequently co-detected with ESBL genes.

CONCLUSION: ESBL-E prevalence was high and associated with poor hygiene and seasonal variation. Higher rainy season prevalence was not explained by reported antibiotic use and may reflect increased environmental exposure risks, which requires further exploration. Improving hygiene-standards and establishing community-level AMR surveillance can provide effective steps forward in mitigating AMR burden in rural sSA.},
}

@article {pmid41525005,
year = {2026},
author = {Mir, PA and Kumar, N and Bhutia, GT and Chaudhary, P and Kaur, G and Gupta, SK},
title = {The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41525005},
issn = {2509-2723},
abstract = {Alzheimer's disease (AD), the most common cause of dementia in the aging population, is marked by amyloid-beta (Aβ) plaques, tau tangles, and progressive neuronal degeneration, placing heavy clinical and socioeconomic burdens on healthcare worldwide. Aging remains the strongest risk factor, with chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and impaired proteostasis creating a vulnerable brain environment that accelerates AD onset and progression. Recent evidence highlights the gut-glia-immune axis as a critical pathway linking age-related microbiome changes to glial dysfunction. Microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, regulate microglial maturation, astrocytic activity, and neuroimmune signaling. However, age-associated dysbiosis disrupts glial homeostasis, amplifies neuroinflammation, and impairs amyloid clearance, thereby worsening neurodegeneration. Preclinical models including germ-free mice and fecal microbiota transplantation along with clinical studies of elderly AD patients, provide compelling evidence of microbiome-driven modulation of disease. From a therapeutic perspective, microbiome-targeted interventions including probiotics, prebiotics, synbiotics, and microbiota-directed small molecules offer promising strategies to restore glial balance, reduce inflammation, and protect cognitive function. This review highlights the therapeutic potential of probiotics, synbiotics, and fecal microbiota transplantation for mitigating neuroinflammation and cognitive decline in Alzheimer's disease. However, given the multifactorial nature of neurodegenerative disorders, these strategies are unlikely to be universally effective and must be tailored to individual patient profiles.},
}

@article {pmid41523758,
year = {2025},
author = {Khan, AS and Kamthan, M and Ali, A},
title = {Understanding the intricate interactions between microbiota and host.},
journal = {World journal of experimental medicine},
volume = {15},
number = {3},
pages = {101277},
pmid = {41523758},
issn = {2220-315X},
abstract = {The review examines the intricate relationship between the microbiota and its host, highlighting how these microbial communities influence various physiological functions beyond simple coexistence. The microbiota plays a crucial role in regulating the immune system, metabolism, and overall health. We explore the diverse microbial populations inhabiting different body regions and their essential contributions to maintaining balance within the host. Recent research has uncovered molecular mechanisms that govern microbiota-host interactions, offering new insights into how these microbes support health and, conversely, how imbalances known as dysbiosis can increase susceptibility to diseases. While much attention has been given to the gut microbiota, this review also explores the influence of microbes in other parts of the body, including their effects on various organs and tissues. Additionally, we discuss emerging evidence on the gut-brain axis, illustrating how the microbiota can impact brain function and behavior. Understanding this connection could open new possibilities for treating neurological and psychological disorders. Finally, we evaluate microbiota-based therapies such as probiotics and fecal microbiota transplantation, emphasizing the importance of personalized approaches. By integrating findings from multiple disciplines, this review provides a comprehensive perspective on the microbiota's vital role in human health and its potential as a therapeutic target.},
}

@article {pmid41523687,
year = {2026},
author = {Zhang, S and Cheng, X and Chen, L and Wang, Y},
title = {2'-Fucosyllactose (2'-FL) alleviates choline-deficient fat diet-induced nonalcoholic steatohepatitis (NASH) by remodeling intestinal flora.},
journal = {Food science and biotechnology},
volume = {35},
number = {1},
pages = {203-213},
pmid = {41523687},
issn = {2092-6456},
abstract = {UNLABELLED: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease lacking effective treatment. This study investigated 2'-Fucosyllactose (2'-FL) for its therapeutic potential. In vitro, 2'-FL reduced lipid accumulation, oxidative stress, and inflammation in Hepa1-6 cells. In a NASH mouse model, 2'-FL alleviated key disease features: hepatic steatosis, inflammation, and oxidative stress. Furthermore, 2'-FL intervention reversed NASH-associated gut microbiota dysbiosis, specifically by increasing Bacteroidota and decreasing Firmicutes at the phylum level. Fecal microbiota transplantation (FMT) validated the role of gut microbiota in these effects. The findings indicate that 2'-FL ameliorates NASH by remodeling the gut microbiota, thereby reducing endotoxemia and improving lipid metabolism. This suggests 2'-FL as a promising dietary intervention for metabolic liver diseases.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-025-02034-3.},
}

@article {pmid41522487,
year = {2026},
author = {Al Qassab, M and Chaarani, N and Hamou, A and Harb, R and Jradi, A and Zeineddine, M and Ghadieh, HE and Khattar, ZA and Azar, S and Kanaan, A and Harb, F},
title = {The Gut Microbiota-Insulin Resistance Axis: Mechanisms, Clinical Implications, and Therapeutic Potential.},
journal = {FASEB bioAdvances},
volume = {8},
number = {1},
pages = {e70080},
pmid = {41522487},
issn = {2573-9832},
abstract = {Emerging evidence highlights the pivotal role of the gut microbiota (GM) in regulating host metabolism and contributing to the development of insulin resistance (IR). Gut dysbiosis alters the production of critical metabolites, including short-chain fatty acids (SCFAs), bile acids, indole derivatives, and trimethylamine N-oxide (TMAO), which influence intestinal barrier integrity, inflammatory pathways, and glucose homeostasis. Recent clinical and translational studies indicate that SCFAs can improve fasting insulin and HOMA-IR, although the magnitude of benefit varies substantially across individuals, highlighting ongoing controversy surrounding their metabolic effects. Altered microbial regulation of bile-acid metabolism has also been implicated in impaired lipid and glucose signaling, reinforcing the relevance of FXR- and TGR5-mediated pathways in IR. Elevated TMAO levels have further been associated with adverse metabolic outcomes, though debate persists regarding its causal role versus its function as a diet-dependent biomarker. Microbiota-targeted strategies, including dietary fiber, probiotics, and fecal microbiota transplantation (FMT), show potential to modulate these metabolic pathways, yet clinical results remain inconsistent. This narrative review synthesizes recent mechanistic discoveries and clinical findings on microbiota-derived metabolites in IR, highlights key controversies, and outlines future priorities for translating microbiome science into effective and personalized interventions for metabolic disease prevention and management.},
}

@article {pmid41522358,
year = {2026},
author = {Jin, Y and Zhang, SJ and Zhuang, S and Li, P and Miao, H and Zhao, YY},
title = {Microbiota-gut-kidney axis in health and renal disease.},
journal = {International journal of biological sciences},
volume = {22},
number = {2},
pages = {750-770},
pmid = {41522358},
issn = {1449-2288},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Kidney/metabolism ; Animals ; *Renal Insufficiency, Chronic/microbiology/metabolism ; *Kidney Diseases/microbiology/metabolism ; Dysbiosis ; Acute Kidney Injury/microbiology/metabolism ; },
abstract = {Gut microbiota plays a central role in programming host metabolic function and immune modulation in both health and disease. Microbial dysbiosis leads to an increase in opportunistic pathogens and a reduction in beneficial bacteria, which collectively result in the excessive production of detrimental metabolites, particularly uremic toxins such as indoxyl sulfate and trimethylamine-N-oxide, while concurrently decreasing beneficial metabolites, such as short-chain fatty acids and tryptophan catabolites, including indole-3-aldehyde. The accumulation of harmful metabolites and depletion of protective metabolites contribute to fibrosis progression through various mediators, including the renin-angiotensin system, reactive oxygen species, Toll-like receptor 4, aryl hydrocarbon receptor, inhibitor of kappa B/nuclear factor kappa B, and Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathways. This review highlights the pathogenic link between gut microbiota and kidney damage via the gut-kidney axis, encompassing acute kidney injury (AKI) and chronic kidney disease (CKD). Innovative therapeutic strategies, including microbial therapeutics (such as probiotics, prebiotics, and synbiotics), natural products (such as neohesperidin, isoquercitrin, and polysaccharides), and fecal microbiota transplantation, have been proposed to restore microbial balance and improve kidney function. Targeted modulation of the gut microbiota offers a promising strategy for developing novel treatments in AKI, CKD, and the transition from AKI-to-CKD. This approach has the potential to prevent or mitigate these conditions and their complications.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Kidney/metabolism
Animals
*Renal Insufficiency, Chronic/microbiology/metabolism
*Kidney Diseases/microbiology/metabolism
Dysbiosis
Acute Kidney Injury/microbiology/metabolism

@article {pmid41521300,
year = {2026},
author = {Deng, W and Chen, D and Wei, Y and Chen, W and Chen, K and Zhong, H and He, X},
title = {Washed microbiota transplantation relieves atopic dermatitis via gut-skin microbiome rebalancing.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-026-04717-1},
pmid = {41521300},
issn = {1471-2180},
support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; 82300440//National Natural Science Foundation of China Youth Program/ ; },
abstract = {BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease in which dysbiosis of gut and skin microbiota contributes to pathogenesis and severity. Washed microbiota transplantation (WMT)-an improved form of fecal microbiota transplantation with enhanced safety and microbiota quality control-has shown efficacy in a single reported adolescent case. However, clinical data on WMT in AD and its effects on the skin and gut microbiota remain limited.

METHODS: Twenty-three patients with moderate-to-severe AD received at least two courses of WMT between January 2022 and December 2023. Disease activity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index, the Eczema Area and Severity Index (EASI), the Numeric Rating Scale (NRS) for itch, and the Dermatology Life Quality Index (DLQI). Peripheral blood counts, cytokine profiles, lymphocyte subsets, and gut and skin microbiota were assessed before and after treatment.

RESULTS: WMT was well tolerated (58 sessions; 5.2% mild adverse events) and significantly improved SCORAD, EASI, DLQI, and NRS scores, with greater EASI reductions in adults than in children. Absolute basophil counts decreased significantly after treatment, whereas other hematologic and cytokine parameters remained stable. Gut microbiota showed an increased Gut Microbiome Health Index, a decreased Microbial Dysbiosis Index, and enrichment of short-chain fatty acid-producing taxa, including the Eubacterium coprostanoligenes group, Lachnospiraceae, and Coprococcus. Skin microbiota shifted from Staphylococcus dominance to higher abundances of Acinetobacter, Perlucidibaca, and other potentially protective genera, inversely correlating with disease severity and systemic inflammation.

CONCLUSIONS: WMT appears safe and effective in alleviating clinical manifestations of AD while reshaping both gut and skin microbiota. These parallel microbial shifts support the gut-skin axis as a therapeutic target and highlight WMT as a promising microbiota-centered intervention for immune-mediated skin diseases.},
}

@article {pmid41520913,
year = {2026},
author = {Yang, X and Liu, Y and Miao, K},
title = {Microbiome-Modulated Immunotherapy in Oncology: Current Applications and Future Prospects.},
journal = {Seminars in cancer biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.semcancer.2026.01.001},
pmid = {41520913},
issn = {1096-3650},
abstract = {Cancer immunotherapy has transformed oncology, yet therapeutic efficacy remains heterogeneous and frequently limited by primary or acquired resistance. Increasing evidence demonstrates that both intra- and extratumoral microbiota critically modulate antitumor immunity, influencing clinical responses of immunotherapy and immune-related adverse events (irAEs). Microbial communities regulate the tumor immune microenvironment through multiple mechanisms, including microbe-associated molecular patterns, microbial metabolites, and outer membrane vesicles, acting on tumor or immune cells. These insights have fostered the development of microbiome-based applications in oncology, ranging from predictive biomarkers to therapeutic interventions such as engineered bacteria, fecal microbiota transplantation, probiotics, prebiotics, outer membrane vesicles, bacteriophages, and dietary modulation. Early-phase clinical studies indicate that microbiota-targeted strategies can enhance immunotherapy efficacy or mitigate irAEs, although strain specificity, interindividual variability, and safety remain significant challenges. Future progress will require mechanistic elucidation, integration of multi-omics analyses, standardization of methodologies, and personalized intervention frameworks to translate microbiome modulation into clinically actionable, precision immunotherapy.},
}

@article {pmid41520280,
year = {2026},
author = {van de Guchte, M and Mondot, S and Cadiou, J and Raghuvanshi, R and Rous, C and Doré, J},
title = {Improving ulcerative colitis prospects through fecal microbiota transfer: atypical donor microbiota can boost success rate.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2609457},
doi = {10.1080/19490976.2025.2609457},
pmid = {41520280},
issn = {1949-0984},
mesh = {*Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/microbiology ; Animals ; Rats ; *Gastrointestinal Microbiome ; Humans ; Disease Models, Animal ; *Feces/microbiology ; Dysbiosis/therapy ; Treatment Outcome ; },
abstract = {Fecal microbiota transfer (FMT) has been used with variable success in the experimental treatment of ulcerative colitis (UC), and efforts to improve its efficacy very much remain a matter of trial and error. We recently predicted that atypical donor microbiota could improve results. Here, we provide experimental support for this prediction in a rat model where we induced a transition of the intestinal ecosystem to an alternative state characterized by chronic low-grade inflammation and dysbiosis. While autologous FMT did barely or not enhance the restoration of a healthy microbiota compared to a control group without FMT, the atypical allogenic microbiota from one of two donor rat strains proved remarkably successful in the restoration of a healthy microbiota, in some cases accompanied by a healthy distal colon histology. These results allow the rationalization of research efforts towards improvement of FMT efficacy in humans, and indicate that (initial) success of FMT should be monitored at the microbiota level as much as at the level of clinical symptoms. More importantly, they provide further support for our earlier published, clinical-data-based, conceptual model of the intestinal ecosystem which suggests promising opportunities for therapeutic innovation in UC treatment. This model notably predicts that, and explains why, symbio-therapy, acting on both microbiota and inflammation, may be more efficient than conventional inflammation-directed therapies, and can be used to guide and monitor treatments.},
}

*Fecal Microbiota Transplantation/methods
*Colitis, Ulcerative/therapy/microbiology
Animals
Rats
*Gastrointestinal Microbiome
Humans
Disease Models, Animal
*Feces/microbiology
Dysbiosis/therapy
Treatment Outcome

@article {pmid41519323,
year = {2026},
author = {Wang, L and Lu, C and Li, S and Wu, T and Ren, X and Song, S and Ai, C},
title = {Laminaria japonica fucoidan ameliorates D-galactose-induced cognitive impairment via the regulation of tryptophan metabolism along the gut-brain axis.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {150151},
doi = {10.1016/j.ijbiomac.2026.150151},
pmid = {41519323},
issn = {1879-0003},
abstract = {Aging is a multifactorial biological process in which chronic inflammation and oxidative stress are central to the development of age-related disorders, including neurodegenerative decline. Fucoidan, a sulfated polysaccharide extracted from brown algae, has well-documented anti-inflammatory and antioxidant effects, and therefore has the potential to be a neuroprotective agent against cognitive impairment associated with aging. In the present study, the major fucoidan fraction (LJF-2) isolated from Laminaria japonica was examined for its neuroprotective properties in a D-galactose induced aging mouse model. Oral administration of LJF-2 for 8 weeks significantly improved spatial learning and memory and suppressed neuroinflammatory responses and oxidative stress while significantly reducing the activation of astrocytes and microglia. These neuroprotective effects were linked to the regulation of key proteins involved in neuronal protection and synaptic function, such as neprilysin and synapsin, by cAMP response element-binding protein signaling. Furthermore, LJF-2 significantly remodeled the gut microbiota through a reduction in the abundance of the Bacteroidota, Proteobacteria, and several putative pathogenic genera, which enhanced the intestinal barrier integrity and modified the microbial metabolite profiles, especially those associated with tryptophan metabolism. Fecal microbiota transplantation experiments further confirmed the role of the gut microbiota modulated by LJF-2 in mediating its neuroprotective effects through reduction of oxidative stress and inflammation. Collectively, these findings suggest that LJF-2 may be a promising therapeutic approach to address the aging-related cognitive decline by modulating the gut-brain axis.},
}

@article {pmid41519109,
year = {2026},
author = {Hoedt, EC and Talley, NJ},
title = {Toward a personalized diet-microbiome strategy in inflammatory bowel disease: Matching donor, diet, and patient.},
journal = {Med (New York, N.Y.)},
volume = {7},
number = {1},
pages = {100918},
doi = {10.1016/j.medj.2025.100918},
pmid = {41519109},
issn = {2666-6340},
mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diet therapy ; *Fecal Microbiota Transplantation/methods ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; *Diet ; },
abstract = {Fecal microbiota transplant plus dietary change to restore the imbalance of an individual's microbiome to relieve disorders such as inflammatory bowel disease has not been established but has promise. In this commentary, we suggest the need to embrace a more nuanced, personalized approach, one that considers microbial functionality, dietary context, and host compatibility.},
}

Humans
*Inflammatory Bowel Diseases/microbiology/therapy/diet therapy
*Fecal Microbiota Transplantation/methods
*Precision Medicine/methods
*Gastrointestinal Microbiome
*Diet

@article {pmid41518808,
year = {2026},
author = {Qu, J and Jiang, X and Ma, Y and Sheng, X and Pi, C and Wang, Y and Xu, Q and Li, R and Wang, P and Qian, D and Wang, J and Yi, Z and Yi, J and Wen, L and Liu, S},
title = {Unveiling the gut-brain axis: How chronic exposure to arsenic-induced microglial pyroptosis drives Alzheimer's disease-like pathology.},
journal = {Journal of hazardous materials},
volume = {503},
number = {},
pages = {141087},
doi = {10.1016/j.jhazmat.2026.141087},
pmid = {41518808},
issn = {1873-3336},
abstract = {Arsenic, a pervasive environmental contaminant in groundwater, poses a severe global threat to public health. Chronic arsenic exposure has been linked to neurological impairment, however, its specific pathogenic mechanism and whether the gut-brain axis plays a key role remain unclear. This study investigated the role of gut microbiota and its metabolite indoxyl sulfate (IS) in mediating chronic exposure to arsenic-induced cognitive impairment and Alzheimer's disease (AD)-like pathology, with a specific focus on microglial pyroptosis. We found that chronic arsenic exposure induced cognitive dysfunction and intestinal barrier injury, disrupted gut microbiota composition, promoted IS accumulation in serum and brain, and activated the AhR/NF-κB/NLRP3 signaling pathway, triggering microglial pyroptosis and elevating AD-like pathological markers in mice. Meanwhile, fecal microbiota transplantation (FMT) from arsenic-exposed mice recapitulated cognitive impairment, elevated IS levels, and neuroinflammation in recipient mice. Furthermore, arsenic upregulated hepatic IS-synthesis genes (CYP2E1, Sult1d1) and downregulated renal IS-excretion gene (ABCG2). In vitro, arsenic and IS co-exposure promoted M1 polarization and enhanced pyroptosis by activating the AhR/NF-κB/NLRP3 signaling pathway, while suppressing phagocytosis-related proteins (TREM2, SYK and CD36). Furthermore, SiAhR treatment could alleviated microglial inflammatory injury and enhancing the microglia's phagocytic capacity induced by arsenic and IS co-exposure in BV2 cells through inhibiting the AhR/NF-κB/NLRP3-mediated pyroptosis signaling pathway. In conclusion, chronic arsenic exposure induced cognitive impairment and AD-like pathological via the gut microbiota-AhR-pyroptosis cascade, where in IS accumulation served a key mediator. These findings provide new insights into preventing arsenic-related cognitive damage.},
}

@article {pmid41517132,
year = {2025},
author = {Lu, S and Gao, M and Kuttappan, D and Amalaradjou, MA},
title = {Low-Fat Cheddar Cheese Influences Gut Microbiota Composition and Diversity in Human Microbiota-Associated Mice.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
pmid = {41517132},
issn = {2304-8158},
support = {430855//Foundation for Food and Agriculture Research New Innovator Award/ ; },
abstract = {Cheese is a complex fermented dairy food containing bioactive nutrients and microorganisms that can influence host physiology. However, most existing evidence of its health effects derives from observational studies or investigations of isolated components rather than the whole food matrix. The present study examined the impact of low-fat Cheddar cheese as a whole food on the gut microbiota using a human microbiota-associated (HMA) mouse model. Germ-free C57BL/6 mice were colonized with human fecal microbiota and randomly assigned to either a control diet or a diet supplemented with low-fat Cheddar cheese (7.5% w/w) for six weeks. Fecal samples were collected longitudinally and analyzed by 16S rRNA gene (V3-V4 region) amplicon sequencing. Human microbiota transplantation successfully established a stable, human-like gut microbial community in the mice. Cheese supplementation significantly increased alpha diversity (Shannon and Chao1 indices) and altered microbial composition, characterized by a higher relative abundance of Firmicutes and a reduction in Bacteroidetes (p < 0.001). At the genus level, Lactococcus and Streptococcus were enriched in cheese-fed mice, reflecting potential viable transfer of cheese-derived lactic acid bacteria. These findings provide experimental evidence that low-fat Cheddar cheese can beneficially influence the human-derived gut microbiota in an animal model and highlight the need for further clinical research to validate these effects in humans.},
}

@article {pmid41516340,
year = {2026},
author = {Liu, M and Wang, Y and Huang, H},
title = {Gut Microbiota-Derived Propionic Acid Mediates ApoA-I-Induced Amelioration of MASLD via Activation of GPR43-Ca[2+]-CAMKII-ATGL Hepatic Lipolysis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
pmid = {41516340},
issn = {1422-0067},
support = {5232004//Beijing Natural Science Foundation/ ; 32071130//National Natural Science Foundation of China/ ; },
mesh = {*Gastrointestinal Microbiome ; *Propionates/metabolism/pharmacology ; Animals ; *Receptors, G-Protein-Coupled/metabolism ; *Apolipoprotein A-I/metabolism/genetics ; *Lipolysis/drug effects ; Liver/metabolism ; Male ; Mice ; Humans ; Fecal Microbiota Transplantation ; Calcium/metabolism ; Mice, Inbred C57BL ; *Fatty Liver/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism ; },
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread hepatic condition characterised by hepatic lipid accumulation and inflammation. Emerging research highlights the contribution of the intestinal microbiota and its metabolic byproducts to the pathogenesis of MASLD through the gut-liver axis. Apolipoprotein A-I (apoA-I), the principal structural component of high-density lipoprotein (HDL), is linked to various metabolic disorders; however, its function in MASLD has not yet been clearly elucidated. This study sought to examine whether apoA-I protects against MASLD, with a focus on the possible role of the gut microbiota and propionic acid (PPA). The contribution of the gut microbiota was evaluated using faecal microbiota transplantation (FMT) and antibiotic cocktail (ABX)-mediated depletion. Microbial composition was assessed via 16S rRNA sequencing, and concentrations of short-chain fatty acids (SCFAs) were quantified. The effects of PPA on MASLD were examined using in vivo and in vitro models. The results showed that apoA-I overexpression alleviated MASLD in a gut microbiota-dependent manner, restored microbial homeostasis, and elevated PPA levels. PPA supplementation improved MASLD phenotypes. Mechanistically, PPA treatment was associated with the activation of the GPR43-Ca[2+]-CAMKII-ATGL pathway, suggesting that PPA plays a role in stimulating hepatic lipolysis and enhancing mitochondrial β-oxidation. These findings reveal a novel pathway through which apoA-I ameliorates MASLD by modulating the gut microbiota and increasing PPA levels, which activate a hepatic lipolysis cascade. The apoA-I-microbiota-PPA axis represents a promising therapeutic target for MASLD intervention.},
}

*Gastrointestinal Microbiome
*Propionates/metabolism/pharmacology
Animals
*Receptors, G-Protein-Coupled/metabolism
*Apolipoprotein A-I/metabolism/genetics
*Lipolysis/drug effects
Liver/metabolism
Male
Mice
Humans
Fecal Microbiota Transplantation
Calcium/metabolism
Mice, Inbred C57BL
*Fatty Liver/metabolism
*Non-alcoholic Fatty Liver Disease/metabolism

@article {pmid41516146,
year = {2025},
author = {Barbu, AC and Stoleru, S and Zugravu, A and Poenaru, E and Dragomir, A and Costescu, M and Aurelian, SM and Shhab, Y and Stoleru, CM and Coman, OA and Fulga, I},
title = {Dopamine and the Gut Microbiota: Interactions Within the Microbiota-Gut-Brain Axis and Therapeutic Perspectives.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
doi = {10.3390/ijms27010271},
pmid = {41516146},
issn = {1422-0067},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dopamine/metabolism ; *Brain/metabolism ; Animals ; Parkinson Disease/metabolism/microbiology/therapy ; *Brain-Gut Axis ; Gastrointestinal Tract/metabolism/microbiology ; Fecal Microbiota Transplantation ; },
abstract = {The microbiota-gut-brain axis (MGBA) comprises a complex bidirectional communication network integrating neural, immune, metabolic, and endocrine pathways. Dopamine, traditionally viewed as a central neurotransmitter, also plays essential roles in the gastrointestinal (GI) tract, where it regulates motility, secretion, barrier homeostasis, and mucosal immunity. Growing evidence indicates that the gut microbiota significantly contributes to intestinal dopamine metabolism through specialized enzymatic pathways, particularly tyrosine decarboxylase in Enterococcus species and catechol dehydroxylase in Eggerthella species. These microbial reactions compete with host processes, alter dopaminergic tone, and degrade orally administered levodopa (L-DOPA), providing a mechanistic explanation for the variability in treatment response in Parkinson's disease (PD). Beyond PD, microbially mediated alterations in dopaminergic signaling have been implicated in mood disorders, neurodevelopmental conditions, metabolic dysfunction, and immune-mediated diseases. This review synthesizes current mechanistic and translational evidence on the dopamine-microbiota interface, outlines microbial pathways shaping dopaminergic activity, and highlights therapeutic opportunities including microbiota modulation, dietary strategies, fecal microbiota transplantation, and targeted inhibitors of microbial dopamine metabolism. Understanding this interface offers a foundation for developing personalized approaches in neurogastroenterology and neuromodulatory therapies.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Dopamine/metabolism
*Brain/metabolism
Animals
Parkinson Disease/metabolism/microbiology/therapy
*Brain-Gut Axis
Gastrointestinal Tract/metabolism/microbiology
Fecal Microbiota Transplantation

@article {pmid41515997,
year = {2025},
author = {Ahmed, I and Nijs, J and Vanroose, M and Vandeputte, D and Kindt, S and Elma, Ö and Hendrix, J and Huysmans, E and Lahousse, A},
title = {Oral and Gut Health, (Neuro) Inflammation, and Central Sensitization in Chronic Pain: A Narrative Review of Mechanisms, Treatment Opportunities, and Research Agenda.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
doi = {10.3390/ijms27010114},
pmid = {41515997},
issn = {1422-0067},
mesh = {Humans ; *Chronic Pain/therapy/microbiology/etiology/metabolism ; Animals ; *Gastrointestinal Microbiome ; *Central Nervous System Sensitization ; *Oral Health ; *Neuroinflammatory Diseases ; Dysbiosis ; },
abstract = {Given the limited efficacy of current interventions and the complexity of chronic pain, identifying perpetuating factors is crucial for uncovering new mechanistic pathways and treatment targets. The oral and gut microbiome has emerged as a potential modulator of pain through immune, metabolic, and neural mechanisms. Contemporary evidence indicates that chronic pain populations exhibit altered oral and gut microbiota, characterized by reduced short-chain fatty acid (SCFA)-producing taxa and an overrepresentation of pro-inflammatory species. These compositional changes affect metabolites such as SCFAs, bile acids, and microbial cell wall components, which interact with host receptors to promote peripheral and central sensitization. Microbiota-derived metabolites modulate peripheral sensitization by altering nociceptive neuron excitability and stimulating immune cells to release pro-inflammatory cytokines that increase blood-brain barrier permeability, activate microglia, and amplify neuroinflammation. Activated microglia further disrupt the balance between excitatory and inhibitory neurotransmission by enhancing glutamatergic activity and weakening GABAergic signaling, thereby contributing to the induction and maintenance of central sensitization. While observational studies establish associations between dysbiosis and chronic pain, animal models and early human fecal microbiota transplantation studies suggest a potential causal role of dysbiosis in pain, although human evidence remains preliminary and influenced by diet, lifestyle, and comorbidities. Overall, microbiota appears to regulate pain via peripheral and central mechanisms, and targeting it through specific interventions, such as dietary modulation to enhance SCFA production, alongside broader lifestyle measures like sleep, physical activity, stress management, and oral hygiene, may represent a new therapeutic strategy for the management of chronic pain.},
}

Humans
*Chronic Pain/therapy/microbiology/etiology/metabolism
Animals
*Gastrointestinal Microbiome
*Central Nervous System Sensitization
*Oral Health
*Neuroinflammatory Diseases
Dysbiosis

@article {pmid41514614,
year = {2025},
author = {Peddireddi, RSS and Kuchana, SK and Kode, R and Khammammettu, S and Koppanatham, A and Mattigiri, S and Gobburi, H and Alahari, SK},
title = {Role of Gut Microbiome in Oncogenesis and Oncotherapies.},
journal = {Cancers},
volume = {18},
number = {1},
pages = {},
doi = {10.3390/cancers18010099},
pmid = {41514614},
issn = {2072-6694},
abstract = {The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care.},
}

@article {pmid41512666,
year = {2026},
author = {Liu, JB and Li, S and Sun, GZ and Lin, ZX and Miao, ZM},
title = {Gut microbiota modulation by novel synbiotic improves production performance and ovarian function in aged laying hens via gut-ovary axis.},
journal = {Poultry science},
volume = {105},
number = {3},
pages = {106394},
doi = {10.1016/j.psj.2026.106394},
pmid = {41512666},
issn = {1525-3171},
abstract = {The management of oxidative stress and ovarian dysfunction associated with aged laying hens, which is highly involved in gut microbiota, has been suggested as a feasible approach to improve production performance. Here, we investigated the effects of a novel synbiotic (Bacillus amyloliquefaciens + inulin, BAI), a gut microbiota regulator, on the improvement of production performance in aged laying hens, and dissected the underlying mechanisms using multi-omics analysis. Our findings showed that, compared to the control, high-dosage BAI supplementation significantly improved production performance; enhanced intestinal health, evidenced by the increase of villus height (p < 0.01), the expression of gut barrier-related genes (Claudin-1 and Claudin-2) (all p < 0.001), and immune levels (SIgA and IFN-γ) (all p < 0.01); meliorated ovarian function, confirmed by reduced oxidative stress (p < 0.001) and pathological lesions, as well as increased follicle numbers (p < 0.01 or p < 0.001), serum contents of reproductive hormone (estrogen, luteinizing hormone, and follicle-stimulating hormone) (p < 0.05 or p < 0.001), and the mRNA levels of yolk precursor synthesis-associated genes (APOVLDL-Ⅱ, VTG-Ⅱ, and VLDLR) (all p < 0.001). The 16S rRNA sequencing showed that BAI augmented the relative amount of Lactobacillus, Akkermansia, and Bacteroides and other short-chain fatty acids (SCFAs)-producers. Blood metabolome analysis demonstrated that the predominant metabolites changed by BAI were principally involved in SCFA metabolism, steroid hormone biosynthesis, steroid biosynthesis, and intestinal immune network for IgA production. Ovarian transcriptome analysis indicated that BAI significantly inhibited pathways of ferroptosis and peroxisome, confirmed by RT-qPCR. Furthermore, fecal microbiota transplantation (FMT) from BAI-treated aged hens improved production performance, ovarian function, and oxidative stress status in antibiotic-administrated hens. In sum, our study uncovers that BAI improves production performance and ovarian dysfunction via gut microbiota in aged laying hens. Thus, modulating gut microbiome is an effective approach to laying rate reduction of aged hens.},
}

@article {pmid41511706,
year = {2026},
author = {Shekar, P and Pradeep, S and Shivamallu, C and Prashant, A and Vishwanath, P},
title = {Immune-microbiota crosstalk in colorectal cancer: mechanistic pathways, biomarkers, and translational therapeutics.},
journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico},
volume = {},
number = {},
pages = {},
pmid = {41511706},
issn = {1699-3055},
abstract = {Colorectal cancer (CRC) is caused by a complex interaction between genetic, environmental, and microbial risk factors, and intestinal microbiota has critical roles in inflammation, immunology, and epithelial integrity. Pathobionts from the intestines (Fusobacterium nucleatum, Bacteroides fragilis, and E. coli that produce colibactin) promote DNA damage, immunity protection from cancer therapy, and resistance to chemotherapy treatments. The beneficial commensals and metabolites of intestinal microbes (namely butyrate) increase the mucosal immune response and inhibit tumor-specific signaling mechanisms. Microbe controlled changes of populations of myeloid, lymphoid, and regulatory cells dictate the state of the tumor-immune system and provide actionable checkpoints and biomarkers for cancer therapy. An enormous variety of clinical interventions based on the gut microbiota (probiotics, prebiotics, and fecal microbiota transfer) and diagnostic approaches is currently being developed. Translational issues are difficult due to the interindividual variability and regulatory complexity of tumors. Research needs include standardizing multi-omics data from multidisciplinary teams and mechanistic validation in organoid and gnotobiotic models as well as prediction algorithms to optimize the microbiome-based medicine for individual patients. Targeting the immune-microbiota axis may provide new therapeutic strategies in the diagnosis, prognosis, and therapy of CRC.},
}

@article {pmid41508489,
year = {2026},
author = {Qu, Q and Zhou, Q and Peng, X and Li, Z and Jia, M and Zhang, Y and Yang, C and Dai, X and Sheng, M and Kang, J and Shi, X},
title = {Monascus fermentation enhances the lipid-lowering properties of ginseng in vivo and component assay.},
journal = {Food research international (Ottawa, Ont.)},
volume = {225},
number = {},
pages = {118067},
doi = {10.1016/j.foodres.2025.118067},
pmid = {41508489},
issn = {1873-7145},
mesh = {*Panax/chemistry ; Animals ; *Fermentation ; *Monascus/metabolism ; Mice ; Gastrointestinal Microbiome/drug effects ; Male ; *Hyperlipidemias/drug therapy ; Mice, Inbred C57BL ; *Hypolipidemic Agents/pharmacology ; Lovastatin/pharmacology ; Fecal Microbiota Transplantation ; Lipid Metabolism/drug effects ; Liver/metabolism ; Ginsenosides ; Lipids/blood ; },
abstract = {Hyperlipidemia is a global health concern characterized by elevated lipid levels and increased cardiovascular risk. Ginseng (Panax ginseng) has lipid-lowering properties, and Monascus fermentation can yield monacolin K, a natural statin. However, it remains unclear whether Monascus-fermented ginseng (MFG) offers synergistic benefits over ginseng or Monascus alone. This study aimed to compare the lipid-lowering efficacy of MFG versus unfermented ginseng, Monascus, and their non-fermented combination in hyperlipidemic mice. Multi-omics analyses (hepatic transcriptomics, serum/fecal metabolomics, and gut microbiota profiling) were integrated to elucidate underlying mechanisms, and fecal microbiota transplantation (FMT) assessed the causal role of MFG-altered microbiota. MFG supplementation markedly improved serum lipid profiles and attenuated hepatic steatosis, outperforming ginseng, Monascus, or their unfermented combination. Phytochemical analysis confirmed that fermentation introduced monacolin K into MFG and increased its rare ginsenoside content, distinguishing it from unfermented ginseng. Mechanistically, MFG increased hepatic p-AMPK and upregulated fatty acid oxidation while downregulating lipogenesis (SREBP-1c, FAS). Metabolomics revealed elevated short-chain fatty acid levels and enhanced bile acid biotransformation in MFG-treated mice. MFG reshaped gut microbiota composition and enriched beneficial taxa. Importantly, FMT from MFG-fed donors recapitulated the lipid-lowering effects in recipients, confirming a microbiota-mediated mechanism. In conclusion, MFG exerts superior lipid-lowering effects through complementary host metabolic and gut microbial modulation, highlighting fermented herbal products as promising interventions against hyperlipidemia.},
}

*Panax/chemistry
Animals
*Fermentation
*Monascus/metabolism
Mice
Gastrointestinal Microbiome/drug effects
Male
*Hyperlipidemias/drug therapy
Mice, Inbred C57BL
*Hypolipidemic Agents/pharmacology
Lovastatin/pharmacology
Fecal Microbiota Transplantation
Lipid Metabolism/drug effects
Liver/metabolism
Ginsenosides
Lipids/blood

@article {pmid41508463,
year = {2026},
author = {Dong, Y and Xie, Y and Yao, R and Mai, Y and Zhang, L and Wang, H and Wang, H and Zhang, J},
title = {Lactobacillus fermentum ZNL16 attenuates ETEC-induced intestinal injury by regulating gut microbiota and short-chain fatty acid metabolism to suppress the IL-17/JAK2-STAT3 pathway.},
journal = {Food research international (Ottawa, Ont.)},
volume = {225},
number = {},
pages = {118038},
doi = {10.1016/j.foodres.2025.118038},
pmid = {41508463},
issn = {1873-7145},
mesh = {Animals ; *Gastrointestinal Microbiome ; *Fatty Acids, Volatile/metabolism ; *Limosilactobacillus fermentum/physiology ; STAT3 Transcription Factor/metabolism ; Mice ; *Probiotics/pharmacology ; Interleukin-17/metabolism ; *Enterotoxigenic Escherichia coli ; Signal Transduction ; Fecal Microbiota Transplantation ; Janus Kinase 2/metabolism ; Mice, Inbred C57BL ; *Escherichia coli Infections/microbiology ; Male ; Intestinal Mucosa/microbiology/metabolism ; Intestines/microbiology ; Butyric Acid ; },
abstract = {Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea, threatening neonates, travelers, and livestock by disrupting the intestinal barrier and weakening immunity. Lactobacillus fermentum has been shown to enhance barrier integrity and modulate immune activity, while gut microbiota and their metabolites are critical regulators of intestinal health. Our findings demonstrate that Lactobacillus fermentum ZNL16 improved intestinal barrier function and reduced inflammation via the IL-17/JAK2-STAT3 signaling pathway, while also promoting microbial balance and short-chain fatty acid metabolism. Antibiotic-induced microbiota depletion confirmed that these protective effects are microbiota-dependent. Furthermore, fecal microbiota transplantation (FMT) from ZNL16-treated mice and sodium butyrate supplementation both alleviated ETEC-induced intestinal damage. Taken together, our findings demonstrate the capacity of L. fermentum ZNL16 to safeguard intestinal barrier integrity and modulate immune responses, supporting its promise as a candidate for probiotic development.},
}

Animals
*Gastrointestinal Microbiome
*Fatty Acids, Volatile/metabolism
*Limosilactobacillus fermentum/physiology
STAT3 Transcription Factor/metabolism
Mice
*Probiotics/pharmacology
Interleukin-17/metabolism
*Enterotoxigenic Escherichia coli
Signal Transduction
Fecal Microbiota Transplantation
Janus Kinase 2/metabolism
Mice, Inbred C57BL
*Escherichia coli Infections/microbiology
Male
Intestinal Mucosa/microbiology/metabolism
Intestines/microbiology
Butyric Acid

@article {pmid41507585,
year = {2026},
author = {Hsu, CL and Shukla, S and Freund, L and Chou, AC and Yang, Y and Bruellman, R and Raya Tonetti, F and Cabré, N and Mayo, S and Lim, HG and Magallan, V and Cordell, BJ and Lang, S and Demir, M and Stärkel, P and Llorente, C and Palsson, BO and Mandyam, C and Boland, BS and Hohmann, E and Schnabl, B},
title = {Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {41507585},
issn = {2058-5276},
support = {BX004594//Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development)/ ; CTORA23-208366//American Association for the Study of Liver Diseases (AASLD)/ ; CTORA23-208366//American Association for the Study of Liver Diseases (AASLD)/ ; K99 AA031328/AA/NIAAA NIH HHS/United States ; R01 AA029106, R21 AA030654, P30 AR073761//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; DE-AC02-05CH11231//U.S. Department of Energy (DOE)/ ; },
abstract = {Auto-brewery syndrome (ABS) is a rarely diagnosed disorder of alcohol intoxication due to gut microbial ethanol production. Despite case reports and a small cohort study, the microbiological profiles of patients remain poorly understood. Here we conducted an observational study of 22 patients with ABS and 21 unaffected household partners. Faecal samples from individuals with ABS during a flare produced more ethanol in vitro, which could be reduced by antibiotic treatment. Gut microbiome analysis using metagenomics revealed an enrichment of Proteobacteria, including Escherichia coli and Klebsiella pneumoniae. Genes in metabolic pathways associated with ethanol production were enriched, including the mixed-acid fermentation pathway, heterolactic fermentation pathway and ethanolamine utilization pathway. Faecal metabolomics revealed increased acetate levels associated with ABS, which correlated with blood alcohol concentrations. Finally, one patient was treated with faecal microbiota transplantation, with positive correlations between gut microbiota composition and function, and symptoms. These findings can inform future clinical interventions for ABS.},
}

@article {pmid41506765,
year = {2026},
author = {Rognstad, ØB and Botteri, E and Hoff, G and Bretthauer, M and Nguyen, HD and Schult, AL and Holme, Ø and Randel, KR},
title = {Use of claims data to identify adverse events after colonoscopy in a randomised colorectal cancer screening trial in Norway: a cross-sectional study.},
journal = {BMJ open},
volume = {16},
number = {1},
pages = {e109883},
doi = {10.1136/bmjopen-2025-109883},
pmid = {41506765},
issn = {2044-6055},
mesh = {Humans ; Cross-Sectional Studies ; Norway/epidemiology ; Male ; Female ; Middle Aged ; *Colonoscopy/adverse effects ; *Colorectal Neoplasms/diagnosis ; Aged ; *Early Detection of Cancer/adverse effects/methods ; Retrospective Studies ; *Gastrointestinal Hemorrhage/etiology/epidemiology ; Intestinal Perforation/etiology/epidemiology ; *Insurance Claim Review ; Occult Blood ; },
abstract = {OBJECTIVES: Accurate identification of adverse events after colonoscopy is essential for quality assurance in colorectal cancer (CRC) screening. Review of medical records is labour intensive as adverse events are infrequent. The object of this study was to investigate the accuracy of claims data in identifying adverse events after colonoscopy in CRC screening.

DESIGN: Cross-sectional, retrospective.

SETTING AND PARTICIPANTS: Males and females aged 50-74 years were randomised to once-only sigmoidoscopy or biennial faecal immunochemical test in a CRC screening trial at two screening centres in Norway. Participants in the present study underwent follow-up colonoscopy from 2012 to April 2020 after initial positive screening test. We reviewed medical records for adverse events within 30 days following 11 205 colonoscopies.

The primary outcome of the study was to assess the sensitivity of claims data from the Norwegian Patient Registry to identify lower gastrointestinal bleeding using emergency contact International Statistical Classification of Diseases and Related Health Problems 10th Revision diagnostic code sets under two definitions: a stringent definition (codes explicitly identifying bleeding) and a broad definition (including suggestive codes). Secondary outcome measures included the sensitivity to identify perforation using a stringent and a broad definition. Additionally, we assessed whether incorporating procedure codes and non-emergency contacts improved accuracy.

RESULTS: 87 cases of lower gastrointestinal bleeding and eight perforations were confirmed. Sensitivity for bleeding differed between the centres (p<0.001). At centre 1, sensitivity was 48.6% (95% CI 31.9% to 65.6%) using the stringent and 89.2% (95% CI 74.6% to 97.0%) using the broad definition. At centre 2, sensitivity was 36.0% (95% CI 22.9% to 50.8%) and 50.0% (95% CI 35.5% to 64.5%), respectively. Combined sensitivity for perforation was 37.5% (95% CI 8.5% to 75.5%) using the stringent and 62.5% (95% CI 24.5% to 91.5%) using the broad definition. Adding procedure codes and non-emergency contacts slightly increased sensitivity but increased false positives.

CONCLUSIONS: Use of claims data underestimated adverse event rates following colonoscopy. Difference in coding practice across hospitals underscores the need for standardised reporting in screening programmes.

TRIAL REGISTRATION NUMBER: NCT01538550.},
}

Humans
Cross-Sectional Studies
Norway/epidemiology
Male
Female
Middle Aged
*Colonoscopy/adverse effects
*Colorectal Neoplasms/diagnosis
Aged
*Early Detection of Cancer/adverse effects/methods
Retrospective Studies
*Gastrointestinal Hemorrhage/etiology/epidemiology
Intestinal Perforation/etiology/epidemiology
*Insurance Claim Review
Occult Blood

@article {pmid41506296,
year = {2026},
author = {He, D and Chen, Y and Xue, M and Gao, X and Yan, A and Sun, Y and Li, X and Liu, J and Hu, G and Fu, S},
title = {Orally Administered Neohesperidin (Neo) Alleviates Lipopolysaccharide-Induced Mastitis by Suppressing TLR4/NF-κB and Activating AMPK/Nrf2/HO-1 Signaling, and Regulating Intestinal Flora Structure.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c12129},
pmid = {41506296},
issn = {1520-5118},
abstract = {The impairment of the blood-milk barrier (BMB) during mastitis severely compromises breastfeeding efficacy, highlighting an urgent need for effective nonantibiotic interventions. Natural anti-inflammatory and traditional Chinese medicine (TCM) compounds have thus garnered increasing attention as promising alternatives. Neohesperidin (Neo), a major bioactive flavonoid derived from the TCM herbs such as Citrus aurantium and its related species, has been historically associated with heat-clearing and detoxifying properties in TCM theory. However, its role in mastitis remains unclear. Herein, we investigated the protective effects of Neo on BMB integrity using an LPS-induced mastitis model. Our results demonstrate that Neo significantly alleviates mammary tissue damage and preserves BMB function. Further mechanistic studies indicate that Neo attenuates LPS-induced inflammatory responses and oxidative stress in mammary epithelial cells by inhibiting the TLR4/NF-κB pathway and concurrently activating the AMPK/Nrf2/HO-1 axis. Additionally, 16S rRNA sequencing and fecal microbiota transplantation (FMT) experiments demonstrated that Neo alleviates mastitis by modulating the gut microbiota (increasing beneficial bacteria and reducing harmful bacteria). In summary, this study confirms that Neo can mitigate mastitis and protect BMB function through its anti-inflammatory, antioxidant, and microbiota-regulating effects. The research not only elucidates the molecular mechanisms by which Neo exerts its mammary protective effects through inflammation-oxidative stress-gut microbiota but also provides new insights for the prevention and treatment of mastitis.},
}

@article {pmid41505077,
year = {2026},
author = {Ghaemi, M and Ghaemi, A and Tavakkoli, H and Mashhadinejad, M and Kheradmand, D},
title = {The MOF-Microbiome Axis: a New Paradigm for Precision Nanomedicine.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41505077},
issn = {1867-1314},
abstract = {The gut microbiome is crucial for human health, and its imbalance, known as dysbiosis, is associated with diseases such as inflammatory bowel disease, metabolic disorders, and neurological disorders. Traditional treatments, such as probiotics and fecal microbiota transplants, often lack precision, making the emerging field of nanomedicine a promising alternative. This review introduces the "MOF-Microbiome Axis," which explores the interactions between metal-organic frameworks (MOFs), versatile, porous materials, and the gut microbiome. It focuses on designing gastrointestinal-targeted MOFs that are biocompatible and responsive to stimuli. We discuss how MOFs can serve as scaffolds, controlled-release vehicles, and metabolite scavengers, highlighting their therapeutic applications in targeted antimicrobial therapy, enhanced probiotic delivery, and immunomodulation. The review also addresses important challenges in biosafety, scalable production, and personalized treatment, suggesting future directions such as bio-hybrid systems and precision microbiome editing. Overall, the MOF-Microbiome Axis offers a new perspective on microbiome engineering and advanced therapeutic approaches.},
}

@article {pmid41504254,
year = {2026},
author = {Lin, P},
title = {The importance of the microbiome in uveitis.},
journal = {Current opinion in ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICU.0000000000001197},
pmid = {41504254},
issn = {1531-7021},
abstract = {PURPOSE OF REVIEW: The purpose of this review was to summarize the literature on preclinical and clinical studies demonstrating the impact of the intestinal microbiome in noninfectious uveitis.

RECENT FINDINGS: Preclinical studies using the experimental autoimmune uveitis (EAU) model have shown commensals such as Desulfovibrio and Prevotella, as well as Ruminococcaceae, associated with uveitis, which overlap with some clinical studies in uveitis patients. Interventions that target the microbiome that can be developed for the treatment of uveitis include antibiotics, fecal metabolites or metabolite agonists that are protective in uveitis, probiotics, dietary interventions, or fecal microbial transplant.

SUMMARY: There is significant data supporting the importance of the intestinal microbiome in noninfectious uveitis through enrichment or depletion of certain gut bacteria as well as their metabolites. Targeting the intestinal microbiome or their metabolites might be a viable option for the treatment of noninfectious uveitis.},
}

@article {pmid41503829,
year = {2026},
author = {Zhang, H and Wang, Y and Ning, B and Wang, Y and Sun, T and Xu, J},
title = {The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2611203},
doi = {10.1080/07853890.2025.2611203},
pmid = {41503829},
issn = {1365-2060},
mesh = {Humans ; *Obesity/complications/microbiology/immunology ; *Breast Neoplasms/microbiology/immunology/pathology/therapy ; *Gastrointestinal Microbiome/physiology/immunology ; Female ; *Dysbiosis/microbiology/complications/immunology ; Prognosis ; Probiotics/therapeutic use ; },
abstract = {BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC.

METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening.

DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies.

CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.},
}

Humans
*Obesity/complications/microbiology/immunology
*Breast Neoplasms/microbiology/immunology/pathology/therapy
*Gastrointestinal Microbiome/physiology/immunology
Female
*Dysbiosis/microbiology/complications/immunology
Prognosis
Probiotics/therapeutic use

@article {pmid41503825,
year = {2026},
author = {Kang, K and Kim, JY and Yim, JJ and Kim, D},
title = {Gut-lung axis and microbiome alterations in mycobacterial infections: from pathogenesis to therapeutic potential.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2612428},
doi = {10.1080/19490976.2025.2612428},
pmid = {41503825},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology/therapy ; *Lung/microbiology/immunology ; Animals ; Probiotics ; Fecal Microbiota Transplantation ; *Mycobacterium Infections/microbiology/therapy ; },
abstract = {Mycobacterial lung diseases, including tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), are increasingly recognized as disorders influenced not only by host immunity but also by microbiota. Emerging evidence identifies the gut-lung axis (GLA) as a key bidirectional communication network linking intestinal and pulmonary homeostasis. Mycobacterial infection itself induces airway and gut dysbiosis through immune and metabolic disturbances, which is further exacerbated by prolonged antibiotic therapy. Dysbiosis within either site reciprocally affects the other via GLA, leading to reduced microbial diversity, impaired epithelial integrity, and systemic inflammation. These alterations disrupt metabolite-mediated immunoregulation and attenuate IL-22-driven epithelial defense, thereby weakening bacterial clearance and promoting chronic inflammation. Distinct microbial features, such as the depletion of beneficial SCFA-producing taxa and enrichment of pro-inflammatory anaerobes, are observed in both TB and NTM-PD. Moreover, therapy-induced microbiome remodeling influences treatment response and disease relapse. Restoring microbial balance through probiotics, prebiotics, postbiotics, dietary modulation, or fecal microbiota transplantation offers a promising adjunctive strategy. This review integrates current evidence linking microbiome dysbiosis to mycobacterial pathogenesis and highlights microbiome-targeted interventions as an emerging therapeutic frontier in pulmonary mycobacterial diseases.},
}

Humans
*Gastrointestinal Microbiome
*Dysbiosis/microbiology/therapy
*Lung/microbiology/immunology
Animals
Probiotics
Fecal Microbiota Transplantation
*Mycobacterium Infections/microbiology/therapy

@article {pmid41503791,
year = {2026},
author = {Jin, J and Yao, G and Zhang, X and Zhang, T and Ye, H and Zhou, X and Yu, Y and Zhao, Y and Qin, Z and Chen, H and Bi, Y and Wang, X and Ren, X and Zhang, Y and Wang, Z and Zhang, Q},
title = {Gut virome dysbiosis contributes to premature ovarian insufficiency by modulating gut bacteriome.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2611645},
doi = {10.1080/19490976.2025.2611645},
pmid = {41503791},
issn = {1949-0984},
mesh = {Female ; Animals ; *Dysbiosis/microbiology/virology ; *Primary Ovarian Insufficiency/microbiology/virology/therapy ; *Gastrointestinal Microbiome ; Rats ; Humans ; Adult ; *Virome ; Fecal Microbiota Transplantation ; *Bacteria/genetics/classification/isolation & purification/virology ; Young Adult ; Feces/virology ; Ovary ; Rats, Sprague-Dawley ; },
abstract = {BACKGROUND: Premature ovarian insufficiency (POI) significantly impairs female fertility and poses substantial health risks; however, its pathogenesis is incompletely understood, and effective therapeutic interventions are limited. Although gut bacteriome has been closely associated with ovarian dysfunction, the role and therapeutic potential of gut viruses, which far outnumber bacteria, remain largely unexplored.

RESULTS: Therefore, we recruited 60 healthy reproductive-aged women and recently diagnosed POI patients and investigated these concerns using various techniques, including whole-genome shotgun sequencing of virus-like particle (VLP) and fecal virome transplantation (FVT) in CTX-induced POI rats. We found considerable interindividual variability in the gut virome. The virome of POI patients exhibited significant dysbiosis, characterized by a marked reduction in virulent phage, significant changes in predominant phages, and a notable increase in horizontal gene transfer of resistance genes and virulence factors. Furthermore, gut VLPs from the healthy reproductive-aged women significantly improved the condition of POI rats. Conversely, gut VLPs from POI patients markedly impaired the ovarian function and reproductive capacity of healthy rats. The above regulatory effect is primarily due to modulations of gut bacteriome, specifically the estrobolome, and intestinal barrier integrity, which subsequently affect hypothalamic-pituitary-ovarian axis hormone levels and regulate ovarian oxidative stress and inflammation, thereby influencing ovarian function.

CONCLUSIONS: Our findings demonstrate the critical roles of the gut virome in regulating ovarian function and provide new insights into the pathogenesis of POI. This study also underscores the therapeutic potential of the gut virome in improving ovarian dysfunction and female infertility including POI.},
}

Female
Animals
*Dysbiosis/microbiology/virology
*Primary Ovarian Insufficiency/microbiology/virology/therapy
*Gastrointestinal Microbiome
Rats
Humans
Adult
*Virome
Fecal Microbiota Transplantation
*Bacteria/genetics/classification/isolation & purification/virology
Young Adult
Feces/virology
Ovary
Rats, Sprague-Dawley

@article {pmid41503704,
year = {2026},
author = {De Palma, G and Costanzini, A and Mohan, V and Sidani, S and Saqib, Z and Pigrau, M and Lu, J and Causada Calo, N and Pinto-Sanchez, I and Verdu, EF and Marcon, M and Barbara, G and Stanghellini, V and De Giorgio, R and Collins, SM and Bercik, P},
title = {The role of gut microbiota in chronic intestinal pseudo-obstruction: exploring fecal microbiota transplantation as a treatment option.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2610597},
doi = {10.1080/19490976.2025.2610597},
pmid = {41503704},
issn = {1949-0984},
mesh = {*Fecal Microbiota Transplantation ; *Intestinal Pseudo-Obstruction/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; Male ; Female ; Middle Aged ; Adult ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/isolation & purification ; Chronic Disease/therapy ; Aged ; Feces/microbiology ; Disease Models, Animal ; Italy ; },
abstract = {Chronic intestinal pseudo-obstruction (CIPO) is characterized by bowel dilation and obstructive symptoms without any structural blockage. Although the microbiota is known to affect gastrointestinal function, its role in CIPO is poorly understood. We aimed to characterize the CIPO microbiota, investigate its role in disease expression and explore the therapeutic role of fecal microbiota transplantation (FMT). CIPO patients (n = 14) and healthy controls (HC, n = 12) were recruited from Italy and Canada. Microbiota profiles and functions were assessed by 16S rRNA sequencing and PICRUSt. Germ-free NIH Swiss mice were colonized with HC and CIPO microbiota, their intestinal transit and bowel distension were assessed by videofluoroscopy and computed tomography (CT), and the expression of host genes by NanoString®. The CIPO microbiota exhibited reduced microbial diversity with dominance of Proteobacteria and altered metabolic function. Mice with CIPO microbiota developed marked bowel distension and slow intestinal transit associated with altered expression of multiple genes related to immunity, the intestinal barrier and neuromuscular function. FMT from a HC improved the microbiota profile, intestinal transit and bowel distension in both CIPO mice and a selected CIPO patient, in whom a marked clinical improvement was sustained for 8 y. Thus, our findings support the use of microbiota-directed therapies to induce clinical improvement in CIPO patients.},
}

*Fecal Microbiota Transplantation
*Intestinal Pseudo-Obstruction/therapy/microbiology
*Gastrointestinal Microbiome
Animals
Humans
Mice
Male
Female
Middle Aged
Adult
RNA, Ribosomal, 16S/genetics
Bacteria/classification/genetics/isolation & purification
Chronic Disease/therapy
Aged
Feces/microbiology
Disease Models, Animal
Italy

@article {pmid41503678,
year = {2026},
author = {Zhou, S and Guo, L and Chen, N and Liu, H and Liu, X and Li, J and Dong, S and Liu, J and Wang, X and Ran, Y and Liu, M and Chu, H and Li, Y and Yang, H and Zhao, J and Zhou, L},
title = {Depression Aggravates Immune-Mediated Hepatitis Through NLRP3 Overactivation Induced by Intestinal Microbiota.},
journal = {CNS neuroscience & therapeutics},
volume = {32},
number = {1},
pages = {e70743},
pmid = {41503678},
issn = {1755-5949},
support = {81860109//National Natural Science Foundation of China/ ; 21JCZDJC00880//Natural Science Foundation of Tianjin Municipality/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Male ; Mice ; Humans ; Female ; *Hepatitis, Autoimmune/metabolism/immunology/complications ; Middle Aged ; Adult ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Depression/metabolism/complications ; Concanavalin A/toxicity ; *Depressive Disorder, Major/metabolism ; Inflammasomes/metabolism ; },
abstract = {BACKGROUND: Depression is associated with adverse effects in patients with autoimmune hepatitis (AIH). However, the underlying mechanism remains unclear. This study explores the impact of depression and related intestinal microbiota on immune-mediated hepatitis.

METHODS: We assessed depression in 260 AIH patients receiving 2-year standardized treatment and 173 healthy controls. In mice, depressive-like behaviors were induced by chronic unpredictable mild stress (CUMS), and immune-mediated hepatitis was induced by intravenous injection of concanavalin A (ConA). Fecal microbiota transplantation (FMT) was performed using samples from patients with major depressive disorder (MDD) and controls.

RESULTS: Depression was common in patients with AIH (106/260, 40.8%) and was associated with cirrhosis. Compared with nondepressed AIH patients, those with depression showed exacerbated intestinal barrier dysfunction and hepatic NLR family pyrin domain containing 3 (NLRP3) inflammasome overactivation. In the ConA-induced hepatitis model, CUMS exposure aggravated these abnormalities, which were then attenuated by mirtazapine. Furthermore, mice colonized with MDD microbiota exhibited greater intestinal barrier disruption and hepatic NLRP3 inflammasome overactivation than those colonized with control microbiota. Notably, gut-derived Lactococcus formosensis, isolated from the livers of MDD microbiota-colonized mice, could translocate to the liver and induce hepatic NLRP3 inflammasome overactivation. In addition, vaccination against L. formosensis prevented translocation and alleviated liver injury in monocolonized mice.

CONCLUSION: Depression aggravates immune-mediated hepatitis through disruption of intestinal barrier integrity and overactivation of hepatic NLRP3 inflammasome. Gut-derived L. formosensis could translocate to the liver and induce liver injury in mice. This study provides the necessity of screening for depression in patients with AIH.},
}

Animals
*Gastrointestinal Microbiome/physiology
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
Male
Mice
Humans
Female
*Hepatitis, Autoimmune/metabolism/immunology/complications
Middle Aged
Adult
Fecal Microbiota Transplantation
Mice, Inbred C57BL
*Depression/metabolism/complications
Concanavalin A/toxicity
*Depressive Disorder, Major/metabolism
Inflammasomes/metabolism

@article {pmid41211649,
year = {2026},
author = {Zhao, QK and Ning, YX and Xu, TC and Zhao, ZA and Pei, YF and Niu, JY and Li, XD and Chen, HS},
title = {Electroacupuncture Alleviates Brain Injury Through Vagus Nerve Activation and Gut Microbiota in a Rat Model of Ischemic Stroke.},
journal = {Journal of the American Heart Association},
volume = {15},
number = {1},
pages = {e045929},
doi = {10.1161/JAHA.125.045929},
pmid = {41211649},
issn = {2047-9980},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Electroacupuncture/methods ; *Vagus Nerve/physiopathology/metabolism ; Rats ; Male ; Disease Models, Animal ; Rats, Sprague-Dawley ; *Infarction, Middle Cerebral Artery/therapy/microbiology ; *Ischemic Stroke/therapy/microbiology/physiopathology/metabolism ; Brain/metabolism ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND: Emerging evidence implicates gut microbiota dysbiosis in exacerbating stroke pathogenesis via the gut-brain axis, suggesting novel therapeutic targets. While electroacupuncture (EA) demonstrates anti-inflammatory effects through vagus nerve activation, its neuroprotective mechanisms via vagus nerve-microbiota crosstalk remain unexplored.

METHODS: Rats with middle cerebral artery occlusion received daily ST36 (Acupoint Zusanli) EA for 1 to 7 days postischemia. Subdiaphragmatic vagotomy and fecal microbiota transplant were implemented to validate pathway specificity. Multimodal assessments included longitudinal neurological scoring, infarct volume, systemic/neuroinflammatory profiling (enzyme-linked immunosorbent assay, immunohistochemistry), intestinal fucosylation dynamics (quantitative polymerase chain reaction, lectin staining), and 16S ribosomal RNA sequencing of gut microbiota.

RESULTS: EA significantly improved neurological outcomes and reduced infarct volumes at 3 to 7 days after middle cerebral artery occlusion (versus controls), which was abolished by vagotomy. Mechanistically, EA restored gut barrier integrity through vagus-dependent upregulation of fucosyltransferase 2 (Fut2)-driven epithelial α1,2-fucosylation, enhancing mucin 2+ goblet cell density and tight junction protein expression (ZO-1/occludin/claudin-1). Concurrent microbiota shifts included Lactobacillales/Bacteroidales enrichment (linear discriminant analysis >4.0) and pathobiont suppression, which was reversed by vagotomy. Crucially, fecal microbiota transplant from EA-treated donors replicated neuroprotection in germ-free recipients, achieving 33% infarct reduction and 30% survival improvement (P=0.012), whereas fecal microbiota transplant from vagotomized donors showed no therapeutic benefits.

CONCLUSIONS: EA at ST36 produced neuroprotection through activating vagal efferent pathways to orchestrate intestinal mucosal repair via Fut2-mediated fucosylation, which reshape microbial ecosystems and attenuate neuroinflammation. These findings establish a previously unrecognized vagus nerve-gut-brain axis mechanism for stroke recovery, positioning microbiota-directed neuromodulation by EA as a translatable therapeutic strategy.},
}

Animals
*Gastrointestinal Microbiome/physiology
*Electroacupuncture/methods
*Vagus Nerve/physiopathology/metabolism
Rats
Male
Disease Models, Animal
Rats, Sprague-Dawley
*Infarction, Middle Cerebral Artery/therapy/microbiology
*Ischemic Stroke/therapy/microbiology/physiopathology/metabolism
Brain/metabolism
Fecal Microbiota Transplantation

@article {pmid41503571,
year = {2026},
author = {Bajaj, JS and Fagan, A and Sterling, RK and Sikaroodi, M and Gallagher, ML and Lee, H and Matherly, SC and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Thacker, LR and McGinley, JP and Khoruts, A and Gillevet, PM},
title = {The multi-omic basis for hepatic encephalopathy recurrence: Analysis of the THEMATIC trial.},
journal = {JHEP reports : innovation in hepatology},
volume = {8},
number = {1},
pages = {101634},
doi = {10.1016/j.jhepr.2025.101634},
pmid = {41503571},
issn = {2589-5559},
abstract = {BACKGROUND & AIMS: The THEMATIC trial demonstrated that fecal microbiota transplantation (FMT) reduces recurrence of hepatic encephalopathy (HE) in patients already receiving lactulose and rifaximin. The aim of this analysis was to identify multi-omic predictors of HE recurrence among THEMATIC trial participants.

METHODS: The THEMATIC trial enrolled patients with cirrhosis and HE who received oral or enema FMT vs. placebo (1-3 administrations) and were followed for 6 months. Outcomes included safety and HE recurrence. Serum, urine, and stool samples were collected at baseline and post-FMT for all participants. Stool metagenomics, serum and urine metabolomics, inflammatory cytokines, and clinical data were analyzed. Differences between patients with and without HE recurrence were assessed using pathway, random forest, and latent factor analyses.

RESULTS: HE recurred in 10 of 60 patients (17%), with significantly higher recurrence in the placebo vs. the FMT groups (40% vs. 8%; p = 0.005). Due to the low recurrence rate in the FMT arms, all patients with recurrence were combined and compared with those without recurrence. Stool metagenomics showed that the abundance of short-chain fatty acid (SCFA) producers (Faecalibacterium, Eubacterium, Bacteroides, Blautia spp.) was lower, while that of GABA-producing taxa (Lactobacillus, Bifidobacterium spp.) was higher, in patients with recurrence. Urine and serum metabolomes separated HE recurrence groups on PLS-DA, with serum butyrate and isobutyrate being most significantly associated (p = 0.008). Pathway analyses revealed upregulation of GABA and neurotransmitter pathways in patients with HE recurrence. Random forest and latent factor analysis indicated that SCFA producers and secondary bile acids were protective, whereas IL-6, GABA producers, nicotine metabolites, and primary bile acids were associated with HE recurrence.

CONCLUSIONS: Secondary analysis of the THEMATIC randomized controlled trial indicates that HE recurrence in patients on lactulose and rifaximin is associated with distinct microbiome and metabolomic profiles, particularly involving SCFAs, GABA metabolism, bile acids, and IL-6.

IMPACT AND IMPLICATIONS: Fecal microbiota transplantation (FMT) reduced hepatic encephalopathy (HE) recurrence in patients receiving lactulose and rifaximin in the THEMATIC trial, but the multi-omic mechanisms underlying this effect were unclear. In this secondary analysis, we found that HE recurrence - regardless of FMT or placebo assignment - was associated with distinct multi-omic signatures, including reduced short-chain fatty acid-producing and increased pathobiont taxa, lower urinary and serum short-chain fatty acids, secondary bile acids, and acetaminophen derivatives, and higher GABA-related and nicotine metabolites, along with elevated IL-6 levels. Notably, patients with greater donor microbiota engraftment had lower rates of HE recurrence. These findings suggest that HE recurrence after FMT reflects a multifactorial process involving alterations in gut metagenomics, systemic metabolomics, inflammation, and donor engraftment.

TRIAL REGISTRATION: www.clinicaltrials.gov: NCT03796598.},
}

@article {pmid41503356,
year = {2025},
author = {Alobaidi, S},
title = {The gut-kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1675458},
doi = {10.3389/fmed.2025.1675458},
pmid = {41503356},
issn = {2296-858X},
abstract = {Chronic kidney disease (CKD) remains a major global health issue, affecting millions and presenting persistent diagnostic and therapeutic challenges. Conventional biomarkers such as serum creatinine and estimated glomerular filtration rate have well-recognized limitations, underscoring the need for novel diagnostic tools and interventions. Emerging evidence highlights the gut-kidney axis as a central contributor to CKD pathogenesis, shaped by microbial dysbiosis and altered metabolite production. Harmful metabolites such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide promote inflammation, endothelial dysfunction, and fibrosis, while loss of protective short-chain fatty acids impairs barrier integrity and immune regulation. This review integrates mechanistic, translational, clinical, and therapeutic perspectives, offering a comprehensive and distinctive synthesis of current knowledge. We emphasize both harmful and protective microbial metabolites, incorporate the often-overlooked oral-gut-kidney axis, and highlight advances in multi-omics and computational approaches for biomarker discovery. Microbiome-targeted interventions-including dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation-are critically evaluated with respect to efficacy, safety, and translational readiness. By bridging basic science, clinical evidence, and therapeutic implications, this review provides a forward-looking framework for integrating microbiome insights into CKD diagnosis and management. Our synthesis complements existing literature while highlighting unmet needs, thereby informing future research priorities and guiding the development of clinically relevant microbiome-based strategies.},
}

@article {pmid41502951,
year = {2025},
author = {Oliveira, RA and McSpadden, E and Pandey, B and Lee, K and Yousef, M and Chen, RY and Triebold, C and Haro, F and Aksianiuk, V and Patel, R and Shriram, K and Ramanujam, R and Kuehn, S and Raman, AS},
title = {Statistical design of a synthetic microbiome that suppresses diverse gut pathogens.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.02.28.582635},
pmid = {41502951},
issn = {2692-8205},
abstract = {Engineering functional microbiomes is challenging due to complex interactions between bacteria and their environments [1-6] . Using a set of 848 gut commensal strains and clearance of multi-drug resistant Klebsiella pneumoniae (Kp -MH258) as a target function, we engineered a functional 15-member synthetic microbiome-SynCom15-through a statistical approach agnostic to strain phenotype, mechanism of action, bacterial interactions, or composition of natural microbiomes. Our approach involved designing, building, and testing 96 metagenomically diverse consortia, learning a generative model using community strain presence/absence as input, and distilling model constraints through statistical inference. SynCom15 cleared Kp -MH258 across in vitro , ex vivo , and in vivo environments, matching the efficacy of a fecal microbiome transplant in a clinically relevant murine model of infection. The mechanism of suppression by SynCom15 was related to fatty acid production coupled with environmental acidification. SynCom15 also suppressed other pathogens- Clostridioides difficile , Escherichia coli , and other K. pneumoniae strains-but through different mechanisms. Sensitivity analysis revealed models trained on strain presence/absence captured the statistical structure of pathogen suppression, illustrating that community representation was key to our approach succeeding. Our framework, 'Constraint Distillation', could be a general and efficient strategy for building emergent complex systems, offering a path towards synthetic ecology more broadly.},
}

@article {pmid41500422,
year = {2026},
author = {Jin, J and Li, F and Hu, Y and Zhang, Z and Zhang, R and Xing, F},
title = {Gut microbiota dysbiosis transmits deoxynivalenol toxicity and triggers liver inflammation.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.01.011},
pmid = {41500422},
issn = {2090-1224},
abstract = {INTRODUCTION: Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is known to compromise gut barrier integrity and induce systemic inflammation.

OBJECTIVES: This study demonstrates that intestinal microbiota play a central role in DON-induced liver inflammation.

METHODS: Through oral exposure and fecal microbiota transplantation (FMT) experiments in mice, we observed that DON disrupts intestinal structure, alters microbial composition, and activates liver inflammation via the TLR4/MyD88/NF-κB pathway.

RESULTS: Notably, liver inflammation was replicated in pseudo-germ-free mice colonized with microbiota from DON-exposed donors, even in the absence of direct DON exposure. Microbial analysis identified Alloprevotella, a mucin-degrading genus associated with increased intestinal permeability, and Pseudomonas, a pathogenic genus enriched in the liver, as key candidate microbial drivers of this effect.

CONCLUSION: These findings underscore that dysbiosis, especially involving specific bacterial genera, can independently trigger liver inflammation, highlighting a microbiota-mediated pathogenic mechanism in mycotoxin toxicity.},
}

@article {pmid41498910,
year = {2026},
author = {Li, Y and Shen, X and Wang, D and Sun, K},
title = {The gut microbiome in colorectal cancer: mechanisms of carcinogenesis and emerging microbiota-targeted therapies.},
journal = {Discover oncology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s12672-025-04367-1},
pmid = {41498910},
issn = {2730-6011},
}

@article {pmid41497693,
year = {2025},
author = {Rusman, RD and Akil, F and Parewangi, ML and Daud, NA and Bachtiar, R and Kusuma, SH and Rifai, A},
title = {Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention.},
journal = {World journal of experimental medicine},
volume = {15},
number = {4},
pages = {107316},
pmid = {41497693},
issn = {2220-315X},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease, closely linked with metabolic syndrome. Recent evidence spotlights the gut-liver axis as a major player in MASLD pathogenesis. Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia, hepatic inflammation, insulin resistance and fibrosis. Microbial metabolites including short-chain fatty acids, bile acids and ethanol impact host metabolism and immunity, and their dysregulation contributes to disease progression. This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition, leaky gut, toll-like receptor signalling and immune dysregulation. It also reviews microbially targeted therapeutic strategies, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation, diet changes, and postbiotic metabolites. Although these interventions may have clinical potential, the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions. Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach. Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic. In conclusion, modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.},
}

@article {pmid41496455,
year = {2026},
author = {Ramesh, A and Subbarayan, R and Shrestha, R and Adtani, PN},
title = {Exploring Fecal Microbiota Transplantation: Potential Benefits, Associated Risks, and Challenges in Cancer Treatment.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {9},
number = {1},
pages = {e70455},
doi = {10.1002/cnr2.70455},
pmid = {41496455},
issn = {2573-8348},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Tumor Microenvironment/immunology ; Immunotherapy/methods ; Animals ; Risk Assessment ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a groundbreaking strategy for modulating the gut microbiome and improving cancer treatment outcomes. This review synthesizes the current evidence on the role of FMT in oncology, focusing on its potential to enhance the efficacy of immunotherapy, restore microbiome homeostasis, and mitigate cancer-associated complications.

RECENT FINDINGS: Preclinical and clinical studies have demonstrated that FMT can reprogram the tumor microenvironment, augment immune checkpoint inhibitor responses, and reduce chemotherapy-induced toxicity. However, risks such as pathogen transmission, immune dysregulation, and unintended microbial shifts necessitate rigorous donor screening and a personalized approach. Challenges in standardization, regulatory frameworks, and mechanistic understanding further complicate their clinical translation. Emerging innovations, including precision microbial consortia, synthetic biology, and biomarker-driven strategies, have the potential to address these limitations.

CONCLUSION: While FMT holds transformative potential in cancer care, its integration into oncological practice requires robust clinical validation, long-term safety assessments, and interdisciplinary collaboration to harness its full therapeutic potential.},
}

Humans
*Fecal Microbiota Transplantation/methods/adverse effects
*Neoplasms/therapy/immunology/microbiology
*Gastrointestinal Microbiome/immunology
Tumor Microenvironment/immunology
Immunotherapy/methods
Animals
Risk Assessment

@article {pmid41496048,
year = {2026},
author = {He, C and Zhou, F and Fang, X},
title = {Meta-analysis of the effectiveness of fecal microbiota transplantation in the treatment of metabolic-associated fatty liver disease: A systematic review based on liver inflammation indicators and fat content.},
journal = {Medicine},
volume = {105},
number = {1},
pages = {e46886},
pmid = {41496048},
issn = {1536-5964},
support = {jkws202318//Health and Sanitation Scientific Research Project of the Metallurgical Safety and Health Branch of the Chinese Society for Metals/ ; },
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Randomized Controlled Trials as Topic ; Body Mass Index ; Treatment Outcome ; *Fatty Liver/therapy ; Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/therapy ; Male ; Middle Aged ; Liver/pathology ; },
abstract = {BACKGROUND: Metabolic-associated fatty liver disease (MASLD) affects over 25% of the global population, progressing from hepatic steatosis to fibrosis. Current therapies show limited efficacy, and gut microbiota dysbiosis via the gut-liver axis highlights fecal microbiota transplantation (FMT) as a novel intervention.

METHODS: Following preferred reporting items for systematic reviews and meta-analyses guidelines, 8 randomized controlled trials were systematically selected from PubMed, Cochrane, Embase, and Web of Science (inception to September 2025). MASLD patients receiving FMT (any protocol) versus standard care were evaluated for alanine aminotransferase (ALT), aspartate aminotransferase (AST), proton density fat fraction, and body mass index (BMI). Risk of bias was assessed using Cochrane ROB 1.0.

RESULTS: FMT significantly reduced ALT (mean difference [MD] = -6.81, 95% confidence interval [-10.29, -3.33], P = .0001) and AST (MD = -7.13, [-10.45, -3.80], P < .0001) versus standard care. Subgroup analysis revealed greater ALT improvement in patients aged <50 years (MD = -14.00, [-22.79, -5.20], P = .002). Proton density fat fraction decreased markedly (MD = -3.50, [-5.12, -1.87], P < .0001), while BMI showed no significant change (MD = -0.69, [-1.49, 0.11], P = .09).

CONCLUSION: FMT effectively improves hepatic inflammation and steatosis in MASLD, with age modulating ALT response. Lack of BMI improvement suggests localized liver effects rather than systemic metabolic impact, supporting FMT as a targeted adjunctive therapy.},
}

Humans
*Fecal Microbiota Transplantation/methods
Alanine Transaminase/blood
Aspartate Aminotransferases/blood
Randomized Controlled Trials as Topic
Body Mass Index
Treatment Outcome
*Fatty Liver/therapy
Gastrointestinal Microbiome
*Non-alcoholic Fatty Liver Disease/therapy
Male
Middle Aged
Liver/pathology

@article {pmid41494302,
year = {2025},
author = {Yi, J and Tang, Y and Chen, Y and Chen, L and Geng, D and Liu, L and Yu, J and Zou, L and Zeng, J and Lan, M and Gao, W and Gao, M},
title = {Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy.},
journal = {Biomaterials},
volume = {329},
number = {},
pages = {123967},
doi = {10.1016/j.biomaterials.2025.123967},
pmid = {41494302},
issn = {1878-5905},
abstract = {Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root-derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota-metabolite-macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.},
}

@article {pmid41494100,
year = {2026},
author = {Wang, D and Dai, S and Li, D and Du, P and Zhao, Y and Chen, Y and Ye, Y and Zhou, M and Ren, W and Liu, X and Zhao, B},
title = {Bovine Milk-Derived Extracellular Vesicles Attenuate Liver Injury by Modulating the Gut-Liver Axis via Faecalibaculum-Mediated SCFA Production.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c12208},
pmid = {41494100},
issn = {1520-5118},
abstract = {Chronic liver injury represents a core pathological substrate in a spectrum of hepatic disorders, wherein gut-liver axis homeostasis critically drives progression. Although bovine milk extracellular vesicles (mEVs) positively regulate intestinal homeostasis, the mechanisms underlying their gut microbiota-linked hepatoprotection remain unclear. Herein, we demonstrated that mEVs (0.6 mg/kg/d) effectively alleviated carbon tetrachloride (CCl4, 1 mg/kg)-induced liver injury, as evidenced by reduced hepatic inflammation and fibrosis. Concurrently, mEVs also markedly attenuated colonic barrier disruption and inflammation concomitant with liver injury. Gut microbiota analysis revealed that mEVs notably enriched the relative abundances of Faecalibaculum and Lactobacillus, which correlated positively with mEV-enhanced colonic short-chain fatty acid (SCFA)/free fatty acid receptor (FFAR) signaling. Furthermore, a causal link between the mEV-reshaped gut microbiota and the resulting hepatoprotection was further established via fecal microbiota transplantation (FMT). In summary, these findings revealed that mEVs attenuated liver injury in a gut microbiota-dependent manner, offering valuable insights into microbiota-targeted and mEV-based therapeutic strategies for hepatic disorders.},
}

@article {pmid41493848,
year = {2026},
author = {Kawaguchi, Y and Terui, K and Fumita, T and Shibata, R and Yoshizawa, H and Ogasawara, S and Kondo, T and Ozawa, Y and Inaba, Y and Hishiki, T},
title = {Cholestasis-reducing effects of bezafibrate on survivors of biliary atresia with native livers: A prospective phase II trial.},
journal = {Hepatology communications},
volume = {10},
number = {1},
pages = {},
pmid = {41493848},
issn = {2471-254X},
mesh = {Humans ; Male ; Female ; *Bezafibrate/therapeutic use/administration & dosage ; *Biliary Atresia/complications/surgery ; *Cholestasis/drug therapy/etiology ; Prospective Studies ; Adult ; *Hypolipidemic Agents/therapeutic use/administration & dosage ; Young Adult ; Adolescent ; Alkaline Phosphatase/blood ; Liver ; Treatment Outcome ; Survivors ; gamma-Glutamyltransferase/blood ; },
abstract = {BACKGROUND: Long-term survivors of biliary atresia (BA) require liver transplantation owing to cholestasis-associated complications. Bezafibrate (BZF), an antihyperlipidemic agent, can improve cholestasis-induced liver damage. Herein, we evaluated the cholestasis-reducing effect of BZF on survivors of BA with native livers, a condition that has not been previously assessed in any study.

METHODS: In this single-center, single-arm, open-label, uncontrolled, prospective phase II trial, patients were enrolled from a central registry system at the Chiba University Data Center. Postoperative patients (n=10) aged older than 18 years (median age, 29 y) with BA and increased serum ALP levels were enrolled between July 2021 and March 2022. Patients with high total bilirubin or alanine aminotransferase levels, recent changes in BA medication, cholangitis within 3 months, renal dysfunction, or liver transplantation were excluded. Participants were administered 400 mg BZF orally in 2 daily doses for 12 weeks and subsequently underwent a 12-week observation. Other drugs were continued. The primary endpoint was the change in ALP levels after 12 weeks of oral BZF administration. The secondary and exploratory endpoints were changes in gamma-glutamyl transpeptidase and triglyceride levels, fecal microbiota, and bile acids.

RESULTS: The mean change in the ALP level was -67 U/L (±20 U/L; p=0.0042). Changes in ALP and gamma-glutamyl transpeptidase levels differed between week 0 and week 6. Adverse events occurred in 5 patients. BZF administration increased the number of Fusicatenibacter without affecting microbiome diversity or bacterial phylum abundance while decreasing lithocholic acid levels and increasing chenodeoxycholic acid levels.

CONCLUSIONS: BZF decreased cholestasis markers in survivors of BA with native livers, indicating its potential as an alternative to delayed liver transplantation for this population.},
}

Humans
Male
Female
*Bezafibrate/therapeutic use/administration & dosage
*Biliary Atresia/complications/surgery
*Cholestasis/drug therapy/etiology
Prospective Studies
Adult
*Hypolipidemic Agents/therapeutic use/administration & dosage
Young Adult
Adolescent
Alkaline Phosphatase/blood
Liver
Treatment Outcome
Survivors
gamma-Glutamyltransferase/blood

@article {pmid41492974,
year = {2026},
author = {Qiu, Y and Lyu, X and Zhang, D and Xu, H and He, X and Chen, J and Liu, H and Liu, Y and Xie, L},
title = {Gut Microbiota in Pulmonary Arterial Hypertension: Murine Models and Human Microbial Signatures, Pathogenic Mechanisms, and Emerging Therapeutic Avenues.},
journal = {Comprehensive Physiology},
volume = {16},
number = {1},
pages = {e70094},
doi = {10.1002/cph4.70094},
pmid = {41492974},
issn = {2040-4603},
support = {U21A20333//National Natural Science Foundation of China/ ; 2023YFC2705701//National Key Research and Development Program of China/ ; XZ202501ZY0116//Science and Technology Projects of Xizang Autonomous Region/ ; XZ202401ZY0013//Science and Technology Projects of Xizang Autonomous Region/ ; 2023NSFSC0530//Sichuan Province Science and Technology Support Program/ ; },
mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Pulmonary Arterial Hypertension/microbiology/therapy/metabolism ; Mice ; Disease Models, Animal ; Fecal Microbiota Transplantation ; },
abstract = {Pulmonary arterial hypertension (PAH) is a chronic, severe cardiopulmonary disease characterized by the progressive increase in pulmonary vascular resistance (PVR) because of the proliferation and fibrosis of the pulmonary arterioles. Although the disease originates in the pulmonary vasculature, it ultimately leads to right heart failure and death. PAH is associated with high mortality rates and poor prognosis, with no therapies currently available to reverse pulmonary vascular remodeling, imposing substantial socioeconomic burdens. Growing interest in the gut-lung axis has highlighted the role of gut microbiota and their metabolites in the occurrence and development of PAH. Evidence showed that gut dysbiosis and metabolite imbalances, involving reduced short-chain fatty acids (SCFAs), increased trimethylamine-N-oxide (TMAO), and dysregulated tryptophan metabolism, contributed to pulmonary vascular remodeling. This review systematically compares gut microbiota and metabolites across PAH murine models (including chronic hypoxia, SU5416/hypoxia [SuHx], monocrotaline [MCT], and non-classical models) and patients (adults and children). The analysis aims to identify disease-specific microbial and metabolic signatures. It is also discussed how the microbiota and their metabolites may influence inflammation around the pulmonary vasculature. Furthermore, the potential of probiotic therapy, fecal microbiota transplantation (FMT), and mesenchymal stem cells (MSCs) therapies as novel treatment strategies for PAH is discussed.},
}

Humans
Animals
*Gastrointestinal Microbiome/physiology
*Pulmonary Arterial Hypertension/microbiology/therapy/metabolism
Mice
Disease Models, Animal
Fecal Microbiota Transplantation

@article {pmid41492376,
year = {2026},
author = {Huang, L and Zheng, Y and Liu, Q and Feng, Y and Ma, Z and Zhao, X and Wei, X and Yu, X and Lv, X and Lv, J and Li, L and Liu, H and Ze, X and Zhang, M},
title = {Milk fat globule membrane ameliorates depressive-like behaviors in chronic unpredictable mild stress rats by modulating the microbiota-gut-brain axis.},
journal = {Bioscience of microbiota, food and health},
volume = {45},
number = {1},
pages = {66-78},
pmid = {41492376},
issn = {2186-6953},
abstract = {Depression is one of the common psychiatric disorders, and it has been reported that the imbalance in the microbiota-gut-brain (MGB) axis contributes to the pathogenesis of depression. Milk fat globule membrane (MFGM) can impact the gut-brain axis by regulating the intestinal flora and metabolite production. The aim of this study was to investigate whether MFGM could ameliorate depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) and further elucidate the potential mechanism through a fecal microbiota transplantation (FMT) experiment. Male Sprague-Dawley rats were provided with an MFGM diet for 5 weeks after the induction with CUMS. Depressive-like behaviors were assessed, and the levels of neurotransmitters, neuroendocrine hormones, microbiota, short-chain fatty acids (SCFAs), and tight junction proteins, including occludin and zonula occludens-1 (ZO-1), were measured. It was revealed that MFGM could alleviate the depressive-like behaviors in CUMS rats. MFGM up-regulated the expression of occludin and ZO-1 and ameliorated intestine pathological changes in CUMS rats. Moreover, MFGM increased the levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine and decreased the levels of neuroendocrine hormones in CUMS rats. Furthermore, it was confirmed that the concentrations of SCFAs, DA, 5-HT, and tight junction proteins significantly increased in the recipient rats that were inoculated with the fecal microbiota from the rats after MFGM treatment. These findings demonstrated that MFGM could alleviate depressive-like behaviors in CUMS rats and was possibly associated with modulation of the gut microbiota and up-regulation of SCFAs and monoamine neurotransmitters.},
}

@article {pmid41484843,
year = {2026},
author = {Sadeghi, R and Abdol Homayuni, MR and Fateh, A and Ebrahimzadeh, N and Riazi-Esfahani, H and Yazdani Moghadam, M and Nikfar, R and Pakzamir, P and Siadat, SD},
title = {The gut-eye axis: microbiota and their role in diabetic retinopathy: a systematic review and meta-analysis.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {7},
pmid = {41484843},
issn = {1471-2415},
abstract = {PURPOSE: To systematically evaluate the relationship between gut microbiota dysbiosis and diabetic retinopathy (DR), exploring microbial diversity, composition, metabolic function, and causal associations via the gut–eye axis.

METHOD: A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches across PubMed, Scopus, Embase, and Web of Science identified studies examining gut microbiota in diabetic patients with and without DR. Eighteen eligible studies—including observational, cohort, and Mendelian randomization (MR) designs—were critically appraised. Meta-analyses pooled standardized mean differences (SMDs) for alpha diversity indices (Chao1, ACE, OTUs, Shannon, Simpson) between DR, diabetes without retinopathy (DM), and healthy controls (HC), using random-effects models with heterogeneity assessments.

RESULTS: Gut microbiota in DR patients showed inconsistent alpha diversity changes but consistent beta diversity shifts, indicating distinct microbial community structures. Meta-analysis across eight studies (268 DR, 269 DM, 99 HC) revealed no significant differences in alpha diversity between DR and DM (e.g., Shannon SMD 0.01, 95% CI -0.44 to 0.45; I²=74%) or DR and HC (e.g., Shannon SMD 0.02, 95% CI -1.30 to 1.33; I²=71%), with moderate to high heterogeneity. DR cohorts exhibited altered Firmicutes/Bacteroidetes ratios, reduced short-chain fatty acid (SCFA)-producing genera (e.g., Faecalibacterium, Roseburia), and increased pro-inflammatory taxa (e.g., Escherichia-Shigella, Pseudomonas). Functional analyses revealed dysregulated amino acid and lipid metabolism, with specific taxa-metabolite correlations.

CONCLUSION: This review substantiates gut microbiota dysbiosis as a potential contributor to DR pathogenesis via the gut–eye axis. While no robust changes in alpha diversity were found, compositional and functional alterations highlight specific microbial taxa and pathways as potential therapeutic targets. Microbiota modulation through diet, probiotics, or fecal transplantation may offer novel strategies to complement conventional DR management. However, high heterogeneity, demographic limitations, and methodological variations warrant further longitudinal and ethnically diverse studies to validate these findings and guide clinical translation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-025-04599-3.},
}

@article {pmid41491927,
year = {2026},
author = {Yao, T and Xiong, Y and Hu, Q and Chen, Y and Li, D and Yan, J and Yang, J and Wang, Y and Cao, H and Zhang, F and Zhuang, R and Sun, J},
title = {Maternal gestational diabetes mellitus leads to adverse growth patterns and disease risk in offspring in vivo: evidence from cross-generational effects on gut microbiota.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-025-04591-3},
pmid = {41491927},
issn = {1471-2180},
support = {2023YFF1104301//National Key R&D Program of China/ ; BK20241756//Basic Research Program of Jiangsu/ ; HB2023063//Medical Key Discipline Program of Wuxi Health Commission/ ; KX-25-A14; KX-25-C108//The Soft Science Project of Wuxi Science and Technology Association/ ; },
}

@article {pmid41490838,
year = {2026},
author = {Gao, W and Yan, S and Zhang, L and Chen, L and Che, J and Huang, W and Chen, Y and Liu, A and Zhu, Y and Yang, Y and Peng, Z and Tan, C and Schnabl, B and Hou, X and Yang, L and Chu, H},
title = {Escherichia coli expressing the kpsM gene exacerbates drug-induced liver injury through up-regulating α1,2-fucosyltransferase and disturbing the host taurine metabolism-from animal models and clinical studies.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.12.012},
pmid = {41490838},
issn = {2090-1224},
abstract = {BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is a leading cause of acute liver failure. Patients with DILI have disorders of the gut microbiota, yet little is known about the influence of gut microbes on this disease. Herein, we investigated the alterations of gut microbiota in DILI patients, and elucidated the mechanism by which Escherichia coli expressing kpsM gene (kpsM[+]E. coli) exacerbates DILI, in order to provide targets for intervention of related signaling pathways to improve DILI.

METHODS: Full-length 16S sequencing was performed on fecal samples from a prospective cohort of patients with DILI (n = 42). Quantitative PCR was employed for analysis of E. coli and its kpsM gene in human feces. The DILI model was established by intraperitoneal injection of acetaminophen (300 mg/kg) into mice (n = 5-12). Two hours later, kpsM[+] or kpsM knockout E. coli strains were gavaged to determine their roles during DILI. Intestinal epithelial Fut2 gene knockout mice (Fut2[ΔIEC]) and hepatic metabolome were used to assess the pathogenic mechanisms of the kpsM[+]E. coli. Plasma metabolome of DILI patients was further validated the discoveries in mice.

RESULTS: The percentage of subjects carrying kpsM were 14.7 %, 40.0 %, 76.5 % in healthy controls, patients with mild DILI, and patients with moderate-to-severe DILI, respectively. Mice transplanted with kpsM[+]E. coli exhibited more severe DILI, primarily achieved through impaired gut barrier function and enhanced expression of intestinal Fut2. Fut2[ΔIEC] mice alleviated the aggravation of DILI caused by E. coli via up-regulating the hepatic levels of taurine and tauroursodeoxycholic acid. In addition, the level of plasma taurine was lower in patients with moderate-to-severe DILI than in those with mild DILI.

CONCLUSIONS: The kpsM[+] E. coli was associated with the severity of DILI in human. This strain can exacerbate DILI in mice through up-regulating intestinal Fut2 expression and disrupting taurine metabolism.},
}

@article {pmid41490552,
year = {2026},
author = {Ren, L and Chen, P and Xu, S and Liang, J and Wang, Y and Lin, C and Yu, Y and Li, Y},
title = {Gut microbiota-based bile acid metabolism mediates the intestinal barrier protection of Phellodendri chinensis Cortex polysaccharide against ulcerative colitis.},
journal = {Journal of ethnopharmacology},
volume = {360},
number = {},
pages = {121143},
doi = {10.1016/j.jep.2025.121143},
pmid = {41490552},
issn = {1872-7573},
abstract = {Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is marked by the occurrence of colonic mucosal damage and immune system dysfunction. A notable challenge in the management of UC is the paucity of long-term effective and safe medications. Phellodendri Chinensis Cortex polysaccharide (PCP), one of the main bioactive compounds in Phellodendri Chinensis Cortex, exerts anti-inflammatory and immunomodulatory effects. However, the effects and mechanisms of PCP on mice with ulcerative colitis remain unclear.

AIM OF THE STUDY: This study explores that PCP attenuates colitis mice via regulation of gut microbiota and bile acid metabolism.

MATERIALS AND METHODS: Monosaccharide composition, molecular weight analysis, infrared spectroscopy, scanning electronic microscopy was used to analyze the chemical characterization of PCP. Mice were administrated by 3 % DSS for establishment of ulcerative colitis model and treated with PCP for 7 days. 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) experiments was performed to evaluate the effect of gut microbiota in PCP-treated colitis mice. Targeted metabolomics analysis of bile acids (BAs) and in vivo inhibition of FXR were performed to analyze the key b BAs and key mechanism of PCP in colitis mice.

RESULTS: PCP alleviated colitis-associated symptoms, repaired, injured intestinal barrier and promoted FXR activation in DSS-induced colitis mice. 16S rRNA gene sequencing found that PCP increased beneficial microbiota such as Bifidobacterium and Lactobacillus, while reducing pathogenic microbiota such as Bacteroides and Romboutsia in colitis mice. FMT experiment confirmed that PCP improved colitis mice and enhanced intestinal barrier integrity through gut microbiota. Simultaneously, PCP altered BA profiles, notably reducing the ratios of primary to secondary BAs and conjugated to unconjugated BAs, with a particularly pronounced effect on the TαMCA/αMCA ratio. Finally, FXR antagonist Gly-β-MCA reversed the protect effect of PCP against colitis.

CONCLUSION: Taken together, our study demonstrates that PCP alleviates DSS-induced colitis symptoms and restores intestinal barrier by gut microbiota-BA metabolism-FXR axis.},
}

@article {pmid41490547,
year = {2026},
author = {Wang, Y and He, Y and Xie, J and Li, J and Guo, J},
title = {E. coli Nissle 1917 Modulates the RNF150/ELAVL1 Ubiquitination Pathway to Ameliorate Obesity-Driven Insulin Resistance in High-Fat Diet-Fed Mice.},
journal = {Cellular and molecular gastroenterology and hepatology},
volume = {},
number = {},
pages = {101719},
doi = {10.1016/j.jcmgh.2025.101719},
pmid = {41490547},
issn = {2352-345X},
abstract = {BACKGROUND & AIMS: Obesity, a global epidemic, fuels metabolic dysfunction through complex gut microbiota‒immune system crosstalk. The probiotic Escherichia coli Nissle 1917 (EcN) holds promise for alleviating obesity-related complications, yet its mechanistic underpinnings remain unclear. This study explored the therapeutic potential of EcN, focusing on its ability to regulate the RNF150/ELAVL1 axis in macrophages to counter high-fat diet (HFD)-induced obesity and insulin resistance.

METHODS: We employed a 12-week dietary intervention in male C57BL/6J mice and administered EcN. Fecal microbiota transplantation (FMT) and myeloid-specific RNF150 and ELAVL1 knockout models were used to establish mechanistic causality. The gut microbiota composition was analyzed via 16S rRNA sequencing, while metabolic parameters, adipose tissue inflammation, and RNF150/ELAVL1 interactions were assessed via glucose/insulin tolerance tests, immunohistochemistry, Western blotting, coimmunoprecipitation, and ubiquitination assays. RNF150 expression was also evaluated in adipose tissue and peripheral blood mononuclear cells from overweight and normal-weight human subjects.

RESULTS: EcN treatment significantly reduced HFD-induced weight gain, adipose accumulation, and insulin resistance while restoring the gut microbiota balance (decreased the Firmicutes/Bacteroidetes ratio and increased Muribaculaceae). FMT from EcN-treated mice recapitulated these benefits. EcN attenuated inflammation across the liver, adipose, and colon, reducing proinflammatory cytokine levels and macrophage infiltration. RNF150 was upregulated in HFD-fed mice and human overweight samples but downregulated by EcN. Myeloid RNF150 deletion mirrored the effects of EcN, promoting anti-inflammatory M2 macrophages and insulin sensitivity. RNF150 mediated ELAVL1 ubiquitination and degradation, while ELAVL1 stabilization enhanced anti-inflammatory responses. Myeloid ELAVL1 deletion worsened metabolic outcomes.

CONCLUSION: EcN ameliorates obesity and insulin resistance by modulating the gut-adipose axis via RNF150/ELAVL1 in macrophages, suggesting novel therapeutic targets for metabolic disorders.},
}

@article {pmid41490238,
year = {2025},
author = {Ni, S and Chen, K and Wang, H and Chen, S and Qiu, Y and Wang, T and Mo, F and Wang, S and Li, B and Bai, Y and Zhao, J and Zhai, X and Li, Z},
title = {A new paradigm of bidirectional regulation of the gut-spinal cord axis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01016},
pmid = {41490238},
issn = {1673-5374},
abstract = {The bidirectional interactions of spinal cord injury, multiple sclerosis, and amyotrophic lateral sclerosis with the gut operate through a distinct gut-spinal cord axis, rather than being fully explained by the conventional gut-brain axis. The spinal cord, with its unique anatomical and physiological features, serves as a central hub of communication. The gut and spinal cord communicate through various pathways, including the immune system and the autonomic and enteric nervous systems. This review summarizes existing clinical and basic research on the relationship between gut homeostasis and spinal cord diseases. First, we present findings from epidemiological studies showing that patients with spinal cord disorders often exhibit altered gut function, which may be influenced by antibiotic exposure and environmental factors. Second, we review the key physiological and anatomical structures of the gut-spinal cord axis, including the intestinal barrier, gut microbiota, and enteric nervous system, all of which are involved in maintaining gut health, as well as sensory neurons, motor neurons, and interneurons in spinal nerve regulation. Third, we describe the roles of the three axes (microbial, immune, and neural) in bidirectional regulation and their pathological mechanisms. Moreover, vicious cycles involving these axes can exacerbate spinal cord disorders. Fourth, we outline potential biomarkers in the gut-spinal cord axis, such as uridine, hypoxanthine, and 5-methoxytryptophan. Fifth, we propose several treatment strategies with potential clinical applications, including fecal microbiota transplantation and the use of probiotics and prebiotics. Finally, this review emphasizes the gut-spinal cord axis as a promising therapeutic target, highlighting the need for multi-omics integration, longitudinal cohort studies, and individualized interventions to resolve existing debates. Overall, the recognition of the gut-spinal cord axis provides a conceptual shift that extends beyond the gut-brain framework.},
}

@article {pmid41488894,
year = {2025},
author = {Lin, B and Zhu, Z and Yang, X and Li, Z and Zhou, H and Luo, M and Guan, J and Zou, Y and Chen, H and Zhuang, Z and Meng, S and Li, W and Yang, Q and Dai, D},
title = {Protocol for the efficacy and safety of fecal microbiota transplantation in children with autism spectrum disorder: a prospective single-center, single-arm interventional study.},
journal = {Frontiers in pediatrics},
volume = {13},
number = {},
pages = {1660773},
pmid = {41488894},
issn = {2296-2360},
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 0.7% of children globally, with 90% experiencing comorbid gastrointestinal (GI) symptoms. Fecal microbiota transplantation (FMT) may modulate ASD symptoms via the microbiota-gut-brain axis (MGBA).

METHODS: This open-label single-arm trial enrolls 30 children (2-12 years) with moderate-to-severe ASD, defined as a Childhood Autism Rating Scale (CARS) score of ≥36. Participants receive 3 nasojejunal FMTs (5 mL/kg) over 5 days. The primary outcomes are GI symptom improvement, assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and ASD severity, assessed using the CARS. Secondary outcomes include social responsiveness (Social Responsiveness Scale, SRS), aberrant behaviors (Aberrant Behavior Checklist, ABC), and gut microbiota changes assessed by metagenomic next-generation sequencing (mNGS).

ETHICS AND DISSEMINATION: Ethical approval obtained from Shenzhen Children's Hospital Ethics Committee. Results will be disseminated via peer-reviewed publications and conference presentations.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=229136, identifier ChiCTR2400083998. Registered on 2024-05-08. Registered title: "Efficacy and safety of fecal microbiota transplantation in treatment of autism spectrum disorder: a prospective single-center intervention study".},
}

@article {pmid41488304,
year = {2025},
author = {Duan, Y and Li, X and Chai, Y and Chen, H and Hou, H},
title = {Adlercreutzia-modulated polyunsaturated fatty acid metabolism underlies nicotine's anti-obesity effects.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1682370},
pmid = {41488304},
issn = {1664-302X},
abstract = {BACKGROUND: The regulatory effects of nicotine on energy balance through central and peripheral mechanisms have been reported. However, its impact on obesity and gut microbiota at safe doses remains unclear.

RESULTS: In this study, it was found that chronic oral nicotine administration daily at relative low dose (0.5 mg/kg) significantly alleviated high-fat diet (HFD)-induced obesity phenotypes in mice, including body weight gain, fat deposits, hepatic steatosis, inflammation and metabolic dysfunction. Gut microbiota depletion and fecal microbiota transplantation (FMT) confirmed that these beneficial effects were microbiota-dependent. Metagenomic sequencing confirmed that nicotine administration reshaped gut microbiota composition, and specifically enriched the commensal genus Adlercreutzia, whose increased abundance correlated with improved biochemical indicators related to obesity. Furthermore, transplantation of Adlercreutzia reproduced anti-obesogenic effects, suggesting it was a key factor for nicotine reducing HFD-induced obesity. Untargeted metabolomics analysis combined association analysis further demonstrated that nicotine modulated host metabolic profiles via gut microbiota-metabolite axis, particularly enhancing Adlercreutzia-linked lipid metabolites involved in polyunsaturated fatty acid (PUFA) metabolism.

CONCLUSION: Collectively, our study elucidates the critical involvement of gut microbiota in nicotine-induced obesity amelioration, uncovers a novel Adlercreutzia-PUFA metabolic axis mediating nicotine's anti-obesity effects, and highlight Adlercreutzia potentiation as a promising microbiota-directed invention strategy for obesity and metabolic syndrome.},
}

@article {pmid41488302,
year = {2025},
author = {Liu, S},
title = {Mechanisms of gut microbiota in host fat deposition: metabolites, signaling pathways, and translational applications.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1675155},
pmid = {41488302},
issn = {1664-302X},
abstract = {Obesity and metabolic diseases are global health challenges, with gut microbiota playing a critical role in host fat deposition through symbiotic interactions. In recent years, the gut microbiota, as an important factor regulating fat deposition, has received widespread attention. Numerous studies have confirmed that gut microbes influence host fat accumulation by regulating energy metabolism, inflammatory response, and gut barrier function. In this review, we summarized the key roles of gut microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, lipopolysaccharides (LPS), branched-chain amino acids (BCAAs), and trimethylamine N-oxide (TMAO) in host epigenetic regulation and lipid metabolism, and explored their regulatory mechanisms through mediated signaling pathways, including Wnt/β-catenin signaling pathway, transforming growth factor beta/SMAD3 pathway (TGF-β/SMAD3), peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In terms of translational applications, we described the research progress and application potentials of intervention strategies, such as probiotics, prebiotics, synbiotics, postbiotics, and fecal transplantation in obesity control and animal production. Finally, we proposed the current bottlenecks and translational challenges in obesity control by precision nutrition and microecological intervention, and look forward to future directions. This review provides a theoretical basis for the in-depth understanding of the interactions between gut microbiota and host metabolism, and serves as a reference for the prevention and control of metabolic diseases by developing nutritional intervention strategies for animals.},
}

@article {pmid41487047,
year = {2026},
author = {Xie, W and Wang, X and Liu, Y and Cai, L and Song, B and Zhang, S and Shao, Y and Wang, W and Xue, X and Li, J and Cui, W and Jiang, Y and Wang, X and Tang, L},
title = {Gut Microbiota-Derived Ursodeoxycholic Acid Mediates the Resistance to Colonic Inflammation in Pigs.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c08687},
pmid = {41487047},
issn = {1520-5118},
abstract = {Microbes in the gut are crucial for host health, yet their role in disease resistance remains unclear. Using fecal microbiota transplantation from disease-resistant Min pigs to Duroc × Landrace × Yorkshire (DLY) pigs, combined with 16S rRNA sequencing and metabolomics, we investigated this relationship. The transferred microbiota alleviated lipopolysaccharide-induced intestinal inflammation and barrier damage in the DLY piglets. Key bacterial genera and bile acid metabolites have been identified, with in vitro evidence showing that the gut microbiome can convert bile acids to secondary forms, primarily ursodeoxycholic acid (UDCA). Subsequent mechanistic validation in a mouse model demonstrated that UDCA acts via the gut-liver axis on the farnesoid X receptor, inhibiting PI3K/AKT/NF-κB pathways and reducing inflammatory responses, thereby preserving tissue structure in the liver and colon. These findings establish a causal link between gut microbiota and disease resistance, indicating that targeting microbial bile acid metabolism may restore intestinal and hepatic health.},
}

@article {pmid41486395,
year = {2026},
author = {Hajjar, R and Mars, RAT and Kashyap, PC},
title = {Harnessing the microbiome for cancer therapy.},
journal = {Nature reviews. Microbiology},
volume = {},
number = {},
pages = {},
pmid = {41486395},
issn = {1740-1534},
abstract = {The microbiome is increasingly recognized as a key player in cancer pathogenesis and treatment response, acting through both local and systemic mechanisms. Microbial communities and their metabolites can directly influence drug metabolism, shape the immune landscape, and alter transcriptional and epigenetic programmes in the gut, systemically and in the tumour microenvironment. Emerging data support the potential of microbiome-targeted interventions (such as faecal microbiota transplantation, diet, prebiotics and probiotics) as adjuncts to conventional cancer therapies, with the goal of enhancing efficacy and reducing toxicity. This Review highlights the promise of the microbiome as a prognostic and predictive biomarker, a modifiable factor in cancer care and prevention, and a therapeutic target. We also discuss major knowledge gaps, limitations in current study designs, and the need for mechanism-guided, personalized strategies to advance clinical translation.},
}

@article {pmid40662627,
year = {2026},
author = {Schmidt, AC and Seyferth, A and Hughes, M and Hughes, WB},
title = {Diverting Ostomy Practices in Burn Surgeons Treating Full-Thickness Perianal Injuries.},
journal = {Journal of burn care & research : official publication of the American Burn Association},
volume = {47},
number = {1},
pages = {231-235},
doi = {10.1093/jbcr/iraf141},
pmid = {40662627},
issn = {1559-0488},
mesh = {Humans ; *Burns/surgery ; *Anal Canal/injuries/surgery ; *Ostomy/methods ; Skin Transplantation ; Wound Healing ; Male ; *Practice Patterns, Physicians'/statistics & numerical data ; Surveys and Questionnaires ; Female ; },
abstract = {Burns to the perianal region pose specific challenges in management due to the complex structure of the surrounding tissue, bacterial contamination, and repetitive stress. Fecal diversion via diverting ostomy may be elected in these injuries because of its potential to enhance wound healing and skin graft adherence; however, its use introduces alternative risks such as prolonged ileus, fistula, leakage, and failure of reversal. This study aimed to determine the perspectives of burn surgeons regarding the use of diverting ostomy for perianal burn injuries. We conducted a survey of 12 physicians who are burn center directors in the Northeast Region of the American Burn Association regarding their practices for patients with full-thickness perianal burn injuries requiring a skin graft. Response rate was 11/12 (92%). Six individuals (54.5%) reported "Never (0%)" to performing a diverting ostomy in this context; the remaining 5 individuals responded "Rarely (<10%)." Reasons stated for performing a diverting ostomy in the "Rarely" group included cases where the patient suffered an intra-anal or anorectal injury. These results were summarized with a relevant review of the literature and experience in our clinical practice. Our findings indicate that diverting ostomy is a relatively uncommon practice for burn surgeons treating full-thickness buttocks injuries. With appropriate wound care and critical care management, good outcomes can be obtained without the need for diverting ostomy. Non-surgical alternatives to fecal diversion are commonly used by burn specialists and should be considered in perianal burn injuries.},
}

Humans
*Burns/surgery
*Anal Canal/injuries/surgery
*Ostomy/methods
Skin Transplantation
Wound Healing
Male
*Practice Patterns, Physicians'/statistics & numerical data
Surveys and Questionnaires
Female

@article {pmid41486262,
year = {2026},
author = {Wu, J and Xiu, M and Wang, X and Zhang, P and Qin, Y and Li, J and Jiang, X and Duan, Y and Liu, Y and He, J},
title = {Dunhuang Gancao Fuling Xingren decoction and its components alleviate CPT-11 induced intestinal mucositis by regulating gut microbiota related innate immunity and inflammatory response in Drosophila and mice.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {4},
pmid = {41486262},
issn = {1749-8546},
support = {DHYX24-15//Foundation from Key Laboratory of Dunhuang Medicine/ ; 2024-QN-35//Lanzhou Youth Science and Technology Talent Innovation Project/ ; 25JRRA1177//Natural Science Foundation of Gansu Province/ ; 25JRRA303//Gansu Natural Science Foundation/ ; },
abstract = {BACKGROUND: Dunhuang Gancao Fuling Xingren decoction (GFXD) is a traditional formulation derived from the Dunhuang Ancient Medical Prescriptions, has been historically utilized for its immunomodulatory and anti-inflammatory properties. However, the protective effect against irinotecan (CPT-11)-induced intestinal mucositis (CIM) remains poorly elucidated.

PURPOSE: To investigate the therapeutic efficacy of GFXD in alleviating CIM and elucidate its underlying mechanism and components using Drosophila melanogaster and C57BL/6 J mouse models.

METHODS: The therapeutic efficacy of GFXD was assessed in both Drosophila and mouse models by phenotype assay, hematoxylin and eosin (H&E) staining, and Alcian blue-periodic acid schiff (AB-PAS) staining. Transcriptomic profiling combined with 16S rRNA sequencing were employed to identify potential mechanisms of GFXD regulating CPT-11-induced mucositis. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including Toll-Imd and JAK-STAT pathways were analyzed via qRT-PCR, immunofluorescence, fecal microbiota transplantation (FMT) experiment, and antibiotic treatment. Furthermore, functional components of GFXD were characterized via liquid chromatography-mass spectrometry (LC-MS), and their efficacy was validated in CPT-11-treated Drosophila.

RESULTS: GFXD significantly mitigated CPT-11-induced systemic and intestinal damage in Drosophila, evidenced by improved survival rate, restored digestive function, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. In mice, GFXD alleviated mucositis symptoms, attenuated histopathological damage, and normalized inflammatory cytokine levels. Mechanistically, GFXD suppressed gut microbiota dysbiosis by enriching probiotics (Lactobacillus, Prevotella) and reducing pathogens (Bacteroides, Enterobacter, Enterococcus and Helicobacter). Transcriptomic and molecular analyses revealed that GFXD inhibited hyperactivation of Toll-Imd pathways and JAK-STAT signaling. Finally, three compounds of GFXD, formononetin, kaempferol, and ergosterol were found to alleviate CPT-11 induced intestinal injury.

CONCLUSIONS: GFXD alleviates CPT-11-induced intestinal mucositis by modulating gut microbiota composition, suppressing JAK-STAT and Toll-Imd pathways. Thus, this study demonstrates GFXD and its bioactive constituents as novel therapeutic agents to mitigate CIM.},
}

@article {pmid41485840,
year = {2026},
author = {Jurgiel, J and Gromowski, T and Król, J and Bomba-Opoń, D and Kościółek, T and Wielgoś, M},
title = {The impact of maternal microbial transfer on the infant gut microbiome after cesarean delivery: a systematic review.},
journal = {American journal of obstetrics and gynecology},
volume = {233},
number = {6S},
pages = {S541.e1-S541.e16},
doi = {10.1016/j.ajog.2025.09.001},
pmid = {41485840},
issn = {1097-6868},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Cesarean Section ; Female ; Infant, Newborn ; Pregnancy ; *Fecal Microbiota Transplantation ; Vagina/microbiology ; Bacteroides ; Lactobacillus ; Bifidobacterium ; },
abstract = {OBJECTIVE: To systematically review the results of maternal microbial transfer in shaping microbial diversity, improving neonatal development, and evaluating the microbial transfer procedure's adverse events.

DATA SOURCES: A comprehensive search was conducted on April 25, 2024, using PubMed/MEDLINE, Academic Search Ultimate, and ClinicalTrials.gov for studies published in English from 2000 to 2023. The following keywords were used: "vaginal seeding," "microbiota," "maternal fecal microbiota transplantation," "maternal microbial transfer," and "bacterial baptism."

STUDY ELIGIBILITY CRITERIA: The review included English-language, peer-reviewed randomized controlled trials and nonrandomized interventional studies investigating maternal microbial transfer in neonates born via elective cesarean delivery.

Data were extracted and analyzed for key outcomes, including severe adverse effects, alpha diversity, beta diversity, and the abundance of key taxa such as Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp.

RESULTS: A total of 10 studies, including 4 randomized controlled trials and 6 nonrandomized interventional studies with 1450 participants, were included in this qualitative review. The findings regarding changes in alpha diversity (a measure of microbial richness within individual samples) were inconclusive, while several studies indicated a potential increase in beta diversity (reflecting differences in microbial composition between samples) associated with the procedure. Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp. were the most frequently assessed taxa, with some studies suggesting beneficial changes in their abundance. Developmental outcomes, such as anthropometric measures and allergy risks, showed limited evidence of benefit, with one study reporting preliminary findings of improved neurodevelopmental scores. No significant increase in severe adverse effects was observed in any of the included studies.

CONCLUSION: The efficacy of maternal microbial transfer in restoring neonatal microbiota and promoting health outcomes remains uncertain, with neonatal outcomes addressed in only 3 of the included studies-one on allergy and one on neurodevelopment. However, while no serious adverse effects have been consistently reported, data on safety remain limited.},
}

Humans
*Gastrointestinal Microbiome
*Cesarean Section
Female
Infant, Newborn
Pregnancy
*Fecal Microbiota Transplantation
Vagina/microbiology
Bacteroides
Lactobacillus
Bifidobacterium

@article {pmid41485542,
year = {2026},
author = {Allani, M and Nath, G and Juyal, G and Chandra Joshi, M and Tiwari, V},
title = {Fecal Microbiota Transplantation Attenuates Neuropathic Pain in Rats via Gut Microbiota-Mediated Immunomodulation of Ion Channels and Nociceptors.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108275},
doi = {10.1016/j.micpath.2026.108275},
pmid = {41485542},
issn = {1096-1208},
abstract = {INTRODUCTION: Neuropathic pain, resulting from somatosensory nervous system damage, presents significant treatment challenges due to limited effectiveness and adverse side effects of current therapies. Emerging evidence highlights the gut microbiome's potential role in pain regulation, yet the specific microbial species and mechanisms underlying chronic neuropathic pain remain largely unexplored.

OBJECTIVES: This study aimed to determine the relationship between gut microbiota and neuropathic pain using fecal microbiota transplantation (FMT) in rats with chronic constriction injury (CCI). Additionally, it sought to identify microbial species associated with pain modulation.

METHODS: CCI was performed in wildtype and antibiotic-treated pseudo-germ-free (PGF) rats. FMT was performed using fecal matter slurry from healthy (hFMT) and CCI-dysbiotic (dFMT) donors, transplanted into nerve-injured and healthy rats, respectively. Pain-related behaviors were assessed and microbial composition was analysed via 16sRNA sequencing. Western blot and RT-PCR assays were conducted on dorsal root ganglion (DRG) and spinal cord tissues.

RESULTS: CCI induced gut microbial dysbiosis, characterized by increased Proteobacteria and Fusobacteriota and decreased Actinobacteria. hFMT from healthy rats alleviated mechanical, thermal, and cold hyperalgesia but did not reverse mechanical allodynia in CCI rats. Conversely, dFMT from CCI rats induced pain-like hypersensitivity in healthy rats, mimicking nerve injury effects. Correlation analysis identified microbial species linked to pain modulation: Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger were associated with reduced pain behaviors, while Pasteurellaceae bacterium, Bacillus sp., and Staphylococcus arlettae were linked to nerve injury-induced dysbiosis. hFMT restored claudin-5 and anti-inflammatory markers TGF-β and IL-10 while downregulating pain-related proteins TRPM8, Nav 1.8, Nav 1.7, and TRPA1 in CCI rats. In contrast, dFMT promoted neuroinflammation by increasing IBA1, TNF-α, and IL-1β, leading to microglial activation in healthy rats.

CONCLUSION: Our findings demonstrate that the composition of gut bacteria influences pain-like behaviors through nerve injury-induced microbial dysbiosis, operating in a bidirectional manner. Additionally, the study suggests that a cocktail of Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger could serve as a promising alternative for managing neuropathic pain.},
}

@article {pmid41485442,
year = {2025},
author = {Ma, C and Liu, Y and Zeng, T and Li, X and Tan, X and Ma, X and Lu, X and Wang, Y and Wu, X},
title = {Zexie-Baizhu herb pair attenuates MASH via the gut-liver Axis by suppressing NLRP3 Inflammasome activation and M1-macrophage polarization.},
journal = {Bioorganic chemistry},
volume = {169},
number = {},
pages = {109451},
doi = {10.1016/j.bioorg.2025.109451},
pmid = {41485442},
issn = {1090-2120},
abstract = {Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of MASLD lacking effective treatments, may be therapeutically targeted by the Traditional Chinese Medicine herb pair Zexie-Baizhu (ZB), known for its lipid-modulating and anti-inflammatory properties. This study investigated ZB's effects and mechanisms in diet-induced MASH mouse models. We began by identifying potential active ingredients in ZB using UPLC-MS/MS. When administered preventively over an 8-week period, ZB significantly improved serum lipids, reduced hepatic inflammation, and alleviated liver lipid accumulation. Mechanistic studies revealed that ZB restores beneficial gut microbiota, enhances intestinal barrier integrity, modulate the hepatic bile acid receptor FXR signaling pathway to regulate bile acid metabolism, and crucially suppresses NLRP3 inflammasome activation and M1 macrophage polarization. Fecal microbiota transplantation confirmed the role of gut microbiota modulation. Collectively, these results demonstrate that ZB alleviates MASH progression primarily via the gut-liver axis by inhibiting NLRP3 inflammasome and M1 macrophage polarization, highlighting this axis as a promising therapeutic target.},
}

@article {pmid41485293,
year = {2025},
author = {Meng, Y and Hou, Y and Zhang, R and Guo, Z and Zhang, Z and Li, J and Yan, Y and Chang, Y and Li, D and Chang, L and Li, M and Gao, H},
title = {Jinlida ameliorates diabetic kidney disease via gut microbiota-dependent production of pyridoxamine targeting renal AGEs/RAGE and TGF-β pathways.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157744},
doi = {10.1016/j.phymed.2025.157744},
pmid = {41485293},
issn = {1618-095X},
abstract = {BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease (ESRD), necessitating novel therapies beyond conventional approaches. Emerging evidence indicates that gut microbiota dysbiosis promotes DKD progression through metabolite-mediated renal injury. Jinlida (JLD) is a clinically validated traditional Chinese medicine with antidiabetic activity, but its microbiota-mediated renoprotective mechanism remains unclear.

PURPOSE: This study investigates whether JLD alleviates DKD by modulating gut microbiota and vitamin B6 metabolism, and elucidates the renoprotective mechanism of its key metabolite, pyridoxamine (PM).

METHODS: To assess JLD's microbiota-dependent effects, we employed antibiotic-induced pseudo-germ-free mice and fecal microbiota transplantation (FMT). Metagenomics and untargeted metabolomics delineated gut microbiota and metabolite compositional changes. Renal PM levels were quantified by LC-MS/MS. The renoprotective effects and mechanisms of direct PM supplementation against DKD were further evaluated in vivo and in vitro.

RESULTS: JLD's therapeutic effects on proteinuria and glomerulosclerosis were shown to partially depend on microbiota homeostasis. Metabolomic analysis demonstrated that JLD significantly upregulated the vitamin B6 metabolic pathway and increased levels of related metabolites, including PM and pyridoxine (PN). Metagenomic analyses indicated that JLD remodeled the gut microbiota composition and enriched pathways related to cofactor biosynthesis, and markedly increased the relative abundance of key enzyme genes involved in the de novo (DXP-dependent) vitamin B6 biosynthesis pathway - namely pdxJ, pdxB, dxs and dxr. Genes related to vitamin B6 activation and conversion (pdxH, aldH) showed no significant changes, suggesting that JLD may promote PM accumulation by enhancing the microbiota's capacity for vitamin B6 biosynthesis rather than its subsequent activation/conversion. Source-tracking pinpointed Paramuribaculum intestinale as the core functional species. In vitro culture experiments showed that JLD markedly promoted the growth of this strain and elevated PM production, and that the strain's conditioned culture medium effectively inhibited formation of advanced glycation end-products (AGEs). Notably, direct supplementation with PM recapitulated the renoprotective effects of JLD in vivo. Mechanistically, PM inhibited the AGEs-RAGE-NF-κB-AP-1 axis and TGF-β receptor signaling, thereby suppressing NF-κB-driven inflammation and Smad2-mediated fibrosis.

CONCLUSION: JLD remodels the gut microbiota and enhances its de novo vitamin B6 biosynthetic capacity, leading to accumulation of PM. Gut-derived PM enters the circulation and functions as an effector molecule targeting the kidney; through PM's direct carbonyl-trapping activity it scavenges AGEs and suppresses the AGEs-RAGE axis as well as downstream inflammatory and profibrotic signaling, thereby exerting renoprotective effects. This study reveals PM as a microbially derived metabolite with therapeutic potential in DKD and offers a new metabolism-directed strategy for DKD treatment.},
}

@article {pmid41484558,
year = {2025},
author = {Zhang, B and Zheng, T and He, Z and Su, S and Yuan, S and Chen, D and Li, H and Guan, W and Zhang, S},
title = {Maternal purified fiber supplementation-enriched Akkermansia muciniphila regulates lactation and offspring growth via the gut-mammary axis.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {41484558},
issn = {1869-1889},
abstract = {Maternal fiber intake alters the maternal gut microbiota and metabolites, which benefits offspring health through unclear mechanisms. Using a sow model, the study showed that supplementing with purified fiber (cellulose:guar gum=3:1) increased weaning weight and resistance to LPS-induced intestinal injury. Milk analysis revealed higher levels of immunoglobulins and milk fat. Fecal microbiota transplantation (FMT) from fiber-fed sows to mice replicated these benefits, increasing milk fat, immunoglobulins, and pup growth. Akkermansia muciniphila (AKK) abundance was positively associated with milk quality in both models. Supplementing with AKK mimicked the effects of fiber, boosting milk fat and immunoglobulins. In in vitro experiments with HC11 mammary epithelial cells showed that AKK metabolites enhanced milk fat synthesis and immunoglobulin transporter expression. Metabolite analysis indicated that AKK influences mammary gland function by increasing acetate and propionate levels, with acetate promoting milk fat synthesis via GPR43 and propionate regulating immunoglobulin transport through GPR41. Therefore, maternal fiber intake promotes intestinal AKK abundance, increases short-chain fatty acids (SCFAs) production, and influences lactation via GPR41/43 signaling.},
}

@article {pmid41483616,
year = {2026},
author = {Zhong, Y and Liu, J and Huang, J and Yu, J and Liu, Y and Zhuo, W and Xu, Y and Zhang, Y and Zhou, Z and Chen, L and Xiao, Q and Liu, D},
title = {Astragaloside IV alleviates ulcerative colitis via gut microbiota - butyrate metabolism axis to reshape Th17/Treg balance.},
journal = {International immunopharmacology},
volume = {171},
number = {},
pages = {116135},
doi = {10.1016/j.intimp.2025.116135},
pmid = {41483616},
issn = {1878-1705},
abstract = {Gut microbiota dysbiosis and Th17/Treg cell imbalance play critical roles in the pathogenesis of ulcerative colitis (UC). Astragaloside IV (AS-IV) exhibits extensive anti-inflammatory and immunomodulatory activities; however, the crosstalk between gut microbiota and Th17/Treg cells modulated by AS-IV remains unreported. Here, chronic colitis was induced in mice by free access to 2.5 % dextran sulfate sodium (DSS) solution over three 7-day cycles, with concurrent AS-IV administration. AS-IV effectively alleviated DSS-induced chronic colitis in mice, as evidenced by increased body weight and colon length, decreased disease activity index (DAI), colon weight, colon weight/colon length, and colon weight index, and enhanced the gene and protein expression of tight junction molecules Claudin-1, Occludin, ZO-1. Notably, AS-IV not only effectively regulated the differentiation balance of Th17/Treg cells, but also significantly improved the composition of gut microbiota and butyric acid metabolism in chronic colitis mice. Intriguingly, Th17/Treg cells and butyric acid were significantly correlated with α/β diversity, as well as the genera Enterorhabdus, Mucispirillum, and Helicobacter. However, AS-IV lost its therapeutic efficacy against colitis and its regulatory effects on Th17/Treg cell balance and butyric acid metabolism following gut microbiota depletion. Critically, FMT from AS-IV-treated mice restored the protective effects against colitis and the regulation of Th17/Treg cell balance and butyric acid metabolism. Collectively, AS-IV inhibits chronic colitis by regulating gut microbiota composition, butyric acid metabolism, and Th17/Treg cell differentiation balance, whose protective effects are dependent on the regulatory mechanism of Th17/Treg cell differentiation balance mediated by gut microbiota-derived butyrate metabolism.},
}

@article {pmid41483363,
year = {2026},
author = {Yang, J and Yan, H and Liu, J and Shen, X and Liu, H and Kang, X and Yang, X and Che, Y and Wang, X and Guo, L and Zhang, F and Fan, W},
title = {Lactobacillus Acidophilus Protects against alcohol-associated Liver Disease in Mice Via Gut Microbiota Modulation and Alleviation of Inflammation and Oxidative Stress.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41483363},
issn = {1867-1314},
support = {202203021211239//Shanxi Provincial Natural Fund Project/ ; 202303021211126//Shanxi Provincial Natural Fund Project/ ; BYJL045//Shanxi Province Higher Education "Billion Project" Science and Technology Guidance Project/ ; },
abstract = {Alcohol-associated liver disease (ALD) is a severe liver disease caused by excessive alcohol consumption. ALD remains a clinical challenge with limited therapeutic options. Following 5-day pretreatment with Lactobacillus acidophilus (Lac), mice were administered ethanol by gavage to induce ALD. Tissues were collected and analyzed for serum markers, hepatic pathology/inflammation/oxidative stress, ileal morphology/tight junctions, and cecal microbiota via 16 S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was performed, and tissues were then collected and analyzed as above. Moreover, the anti-inflammatory and antioxidant properties of Lac-derived particulate matter (pLac) were evaluated on RAW264.7 macrophages in vitro. Lac administration improved gut microbiota composition, enhanced intestinal barrier integrity and reduced lipopolysaccharide (LPS) translocation to the liver, thereby inhibiting the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) pro-inflammatory pathway and activating the adenosine monophosphate activated protein kinase (AMPK)- peroxisome proliferator activated receptor α (PPARα) signaling axis. This led to significant attenuation of hepatic inflammation, oxidative stress and steatosis. The FMT experiments further validated that Lac-mediated protection is dependent on gut microbiota modulation. In vitro studies revealed that pLac exhibit direct anti-inflammatory and antioxidant properties. These findings elucidate the mechanistic basis for Lac in alleviating acute ALD, positioning it as a promising treatment or dietary intervention to enhance clinical management.},
}

@article {pmid41483189,
year = {2026},
author = {Rathee, S and Sen, D and Jain, A and Jain, SK},
title = {Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41483189},
issn = {1432-1912},
abstract = {This comprehensive review explores the multifaceted landscape of hepatic encephalopathy (HE), encompassing its epidemiology, pathophysiology, classification, and evolving therapeutic approaches. Delving into the prevalence and incidence of HE, it is found that the burden of this condition is on individuals and healthcare systems. The intricate mechanisms underlying HE, including abnormalities in synapse transmission, the ammonia hypothesis, the false neurotransmitter theory, the GABAergic theory, and the benzodiazepine theory, are scrutinized, providing a nuanced understanding of the disorder. The review examines altered gene expression, hyponatremia, neurosteroids, oxidative stress, electrolyte imbalance, and manganese accumulation as contributing factors to HE. Classifying HE and identifying precipitating risk factors form crucial aspects of the discussion, shedding light on the most widely used diagnostic tools. Conventional approaches for HE management are discussed, focusing on reducing elevated ammonia formation, improving ammonia-detoxifying liver capacity, and inhibiting false neurotransmitters. Antibiotics, metabolic ammonia scavengers, albumin, probiotics, dietary management, zinc, and secondary prophylaxis are analyzed as current therapeutic targets. Furthermore, the review examines emerging therapies at various stages, including clinical and pre-clinical development, such as glycerol/sodium phenylbutyrate, ornithine phenylacetate, fecal microbiota transplantation, engineered bacteria, liposome-supported peritoneal dialysis, GABAA receptor modulating steroid antagonists (GAMSA), activated carbon microspheres, and glutamine synthetase replacement. This review consolidates knowledge on HE, providing a comprehensive resource for clinicians, researchers, and healthcare professionals involved in managing this complex disorder. The synthesis of epidemiological data, pathophysiological insights, and therapeutic advancements offers a holistic view of HE, paving the way for improved diagnosis and targeted interventions.},
}

@article {pmid41482667,
year = {2026},
author = {Chen, Y and Du, H and Zhou, W and Qin, M and Li, M and Jin, Y and Xu, Y and Ma, C and Xia, J and Mo, Y and Chen, N and Huang, H and Li, H and Xie, Z and Wang, P and Hong, Y},
title = {Tamoxifen induced hepatotoxicity via gut microbiota-mediated hyodeoxycholic acid depletion and Farnesoid X receptor signaling disruption.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2610077},
doi = {10.1080/19490976.2025.2610077},
pmid = {41482667},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Tamoxifen/adverse effects/toxicity ; Mice ; *Chemical and Drug Induced Liver Injury/metabolism/microbiology ; Dysbiosis/microbiology/chemically induced ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Liver/metabolism/drug effects ; Bile Acids and Salts/metabolism ; Humans ; Fecal Microbiota Transplantation ; Male ; Feces/chemistry ; Bacteria/classification/genetics/isolation & purification/metabolism ; },
abstract = {Tamoxifen (TAM) is a widely used estrogen receptor modulator for breast cancer treatment. However, TAM exhibits significant hepatotoxicity in the clinic, affecting nearly 50% of patients and thereby limiting its clinical utility. The specific mechanisms underlying TAM-induced liver injury remain poorly understood. In this study, we elucidated the mechanistic role of the gut microbiota in the hepatotoxicity associated with TAM. TAM administration induced substantial liver injury and gut microbiota dysbiosis in mice, characterized by an increased abundance of Escherichia and a reduction in Lachnospiraceae NK4A136 group. These microbial shifts resulted in decreased levels of total fecal bile acids (BA), particularly hyodeoxycholic acid (HDCA), which was inversely correlated with TAM-induced liver injury. Additionally, TAM disrupted BA homeostasis by enhancing intestinal Farnesoid X receptor (FXR) activity and concurrently stimulating hepatic BA synthesis through an alternative nonintestinal FXR mechanism. Notably, gut microbiota depletion reversed these effects, demonstrating the critical role of the microbiota in modulating the gut‒liver FXR axis in TAM-induced liver injury. Fecal microbiota transplantation (FMT) further confirmed that TAM directly stimulated hepatic BA synthesis through a microbiota-dependent mechanism. The disruption of the gut‒liver BA‒FXR axis impaired enterohepatic BA circulation, contributing to the liver toxicity associated with TAM administration. Importantly, HDCA supplementation restored the gut‒liver BA‒FXR axis and alleviated TAM-induced liver injury. These findings highlight the intricate relationship between TAM, gut microbiota, and BA metabolism, suggesting that targeting the gut-liver FXR axis with HDCA may serve as a promising therapeutic strategy for alleviating TAM-associated liver injury.},
}

*Gastrointestinal Microbiome/drug effects
Animals
*Receptors, Cytoplasmic and Nuclear/metabolism/genetics
*Tamoxifen/adverse effects/toxicity
Mice
*Chemical and Drug Induced Liver Injury/metabolism/microbiology
Dysbiosis/microbiology/chemically induced
Signal Transduction/drug effects
Mice, Inbred C57BL
Liver/metabolism/drug effects
Bile Acids and Salts/metabolism
Humans
Fecal Microbiota Transplantation
Male
Feces/chemistry
Bacteria/classification/genetics/isolation & purification/metabolism

@article {pmid41482085,
year = {2025},
author = {Yang, B and Xia, Q and Ji, X and Su, K and Yu, T and Xiao, Z and Shi, C and Luo, Z and Wang, X and Xu, W and Gao, Y and Hua, H and Shan, J},
title = {Ganjie Decoction protects against respiratory syncytial virus infection by activating PI3K/AKT-apoptosis axis and regulating gut microbiota metabolism.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121142},
doi = {10.1016/j.jep.2025.121142},
pmid = {41482085},
issn = {1872-7573},
abstract = {Ganjie Decoction (GJD), a traditional Chinese medicine (TCM) formula commonly used for respiratory diseases, has shown therapeutic potential against RSV pneumonia. However, its pharmacological mechanisms against respiratory syncytial virus (RSV) pneumonia are not fully understood.

AIM OF STUDY: This study aimd to characterize the active components of GJD and systematically investigate its therapeutic effects and underlying mechanisms in RSV-induced pneumonia.

MATERIALS AND METHODS: To evaluate the therapeutic efficacy of GJD in RSV-infected mice, we monitored body weight, performed qPCR, and conducted histopathological examination of lung tissues. The chemical constituents of GJD were characterized using UPLC-MS. Key bioactive compounds and their potential targets were predicted using network pharmacology and molecular docking. The underlying mechanisms were further elucidated using immunohistochemistry and western blotting. The interactions between GJD and the gut microbiota were explored using antibiotic depletion, fecal microbiota transplantation (FMT), metagenomic sequencing, and in vitro co-culture assays. Untargeted metabolomics was employed to assess GJD-induced metabolic alterations. Finally, the role of 4-hydroxyphenylacetic acid (4-HPA) was investigated through cell viability assays, immunofluorescence staining, and western blot analysis in vitro.

RESULTS: GJD significantly mitigated weight loss, attenuated pulmonary viral load, and suppressed inflammation in RSV-infected mice. Network pharmacology and molecular docking revealed that specific compounds in GJD target the PI3K/AKT signaling pathway. This finding was validated by western blotting and immunohistochemistry, which demonstrated that GJD suppresses PI3K/AKT pathway activation, thereby attenuating apoptosis and ameliorating RSV-induced pneumonia. Notably, these protective effects were markedly attenuated in mice with depleted gut microbiota. Furthermore, the therapeutic effects of GJD against RSV pneumonia were transferable via gut microbiota transplantation. GJD restored RSV-induced dysbiosis of the gut microbiota, with Lactobacillus reuteri emerging as one of the most enriched microbes following treatment. Metabolomics analysis identified 4-HPA as a microbiota-dependent metabolite significantly upregulated by GJD. Remarkably, administration of 4-HPA reproduced GJD's therapeutic effects in RSV-infected mice and activated the KEAP1/NRF2 antioxidant pathway, suggesting that 4-HPA functions as a key mediator of GJD's anti-RSV activity.

CONCLUSIONS: These findings suggest that GJD alleviates RSV pneumonia through a synergistic mechanism that modulates the PI3K/AKT-apoptosis pathway, restores gut microbial balance, and normalizes metabolic disturbances. This study systematically elucidates the mechanistic basis underlying the therapeutic effects of GJD against RSV pneumonia.},
}