@article {pmid42001079,
year = {2026},
author = {Yang, Y and Kang, C and Pang, R and Huang, S and He, X and Gou, X and Yang, Y and Yan, Y and Ma, X},
title = {Dihydromyricetin exerts neuroprotective effects in acute spinal cord injury by inhibiting NLRP3/Caspase-1 inflammasome through gut microbiome modeling.},
journal = {Journal of inflammation (London, England)},
volume = {23},
number = {1},
pages = {},
pmid = {42001079},
issn = {1476-9255},
support = {2024060//Chengdu Municipal Health Commission Medical Research Project/ ; 25MSZX488//Sichuan Provincial Administration of Traditional Chinese Medicine Research Project/ ; },
abstract = {BACKGROUND: The gut microbiota is closely associated with spinal cord injury (SCI). Dihydromyricetin (DHM), a potent anti-inflammatory compound with neuroprotective properties, has been shown to improve outcomes in various diseases. However, the role of gut microbiota mediating the mechanism neuroprotective effects of DHM in SCI is unknown.

METHODS: Male Sprague-Dawley rats were randomly divided into three groups: SHAM, SCI, and DHM group. Motor function was assessed using the cylinder rearing test, and alterations in gut microbiota composition and metabolites were analyzed via 16S rRNA sequencing. Subsequently, Western blotting and immunofluorescence staining were employed to evaluate intestinal barrier integrity, as well as changes in proteins associated with the TLR4/NF-κB pathway and NLRP3/Caspase-1. Finally, fecal microbiota transplantation experiments were conducted to elucidate the necessity of gut microbiota in mediating the anti-inflammatory effects of DHM.

RESULTS: DHM exhibits a therapeutic effect by attenuating the severity of pathological SCI and promoting motor function recovery. Notably, DHM restored a balanced microbiota pattern by increasing the relative abundance of Actinobacteria and Bacteroidetes, while concurrently decreasing that of Proteobacteria. Furthermore, DHM promoted intestinal barrier recovery, reduced blood lipopolysaccharide (LPS) levels, and suppressed the activation of the TLR4/NF-κB pathway and reduced the activity of the NLRP3/Caspase-1 inflammasome, thereby effectively decreasing the subsequent release of inflammatory factors in spinal cord tissue. Furthermore, the results from the two FMT groups demonstrated that the gut microbiota serves as a critical target for DHM to exert its anti-inflammatory effects.

CONCLUSION: The results of this study demonstrate that restoring microbial balance, repairing intestinal barrier integrity, reducing serum LPS levels, and suppressing the TLR4/NF-κB pathway as well as NLRP3/Caspase-1 inflammasome activity constitute the key regulatory mechanisms underlying the neuroprotective effects of DHM following SCI, thereby opening up possibilities for a novel microbiome-directed therapeutic approach to SCI.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12950-026-00499-5.},
}

@article {pmid42230351,
year = {2026},
author = {Domagała, A and Kiecka, A},
title = {Gut Microbiota and Autoimmune Diseases: The Therapeutic Potential of Probiotics.},
journal = {Current microbiology},
volume = {83},
number = {7},
pages = {},
pmid = {42230351},
issn = {1432-0991},
abstract = {In recent years, increasing attention has been directed toward the role of gut microbiota in the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis (RA), and multiple sclerosis (MS). Numerous studies have shown that gut dysbiosis-an imbalance in the intestinal microbial community-can influence host immune responses by modulating inflammatory pathways, gut barrier integrity, and immune cell function. Patients with T1D, RA, and MS often exhibit a decreased abundance of anti-inflammatory bacteria (e.g., Faecalibacterium prausnitzii) and an overrepresentation of pro-inflammatory taxa (e.g., Prevotella copri). Probiotics and fecal microbiota transplantation have shown therapeutic potential by restoring microbial balance, enhancing short-chain fatty acid production, supporting regulatory T cell function, and suppressing pro-inflammatory Th1 and Th17 responses. Despite promising results, the efficacy and safety of these interventions remain uncertain, especially in immunocompromised individuals. The lack of standardization in probiotic formulations, limited large-scale clinical trials, and unknown long-term effects restrict their widespread application. Moreover, individual variability in microbiota composition and disease phenotype complicates the development of universally effective treatments. Further rigorous research is necessary to better understand the immunological mechanisms involved and to develop safe, personalized, and effective microbiota-based therapeutic strategies. Until then, probiotics and FMT should be considered as adjunctive therapies within comprehensive treatment plans for autoimmune diseases rather than standalone solutions.},
}

@article {pmid42230372,
year = {2026},
author = {Ram, E and Carter, D},
title = {Reframing loss of efficacy in sacral neuromodulation: a neurofunctional service model for coloproctology.},
journal = {Techniques in coloproctology},
volume = {30},
number = {1},
pages = {},
pmid = {42230372},
issn = {1128-045X},
abstract = {BACKGROUND: Sacral neuromodulation (SNM) is an established therapeutic option for fecal incontinence, low anterior resection syndrome (LARS), and selected bowel dysfunction phenotypes encountered in colorectal practice. Despite durable benefit in many patients, secondary loss of efficacy (LOE) remains a common long-term management problem and is often interpreted primarily through a mechanical lens.

OBJECTIVE: To refine a conceptual neurofunctional service model for LOE in SNM and to translate it into a more clinically applicable framework for coloproctological practice.

FRAMEWORK: For the purposes of this paper, LOE is defined as deterioration after a previously effective phase, operationalized by one or more of the following: loss of at least 50% of the initial clinically meaningful benefit; deterioration of five or more points on a validated symptom instrument (Wexner Continence Score, LARS Score, or equivalent), or documented worsening in a structured patient symptom diary; or sustained patient-reported decline over at least two consecutive assessments, after exclusion of technical failure. We propose a structured pathway comprising confirmation of LOE, systematic technical exclusion, minimum neurofunctional reassessment, phenotype-guided reprogramming, predefined reassessment intervals, and explicit thresholds for revision or explantation. Terms such as neuroadaptive drift and phenotype mismatch are presented as explanatory hypotheses rather than established mechanisms.

CLINICAL IMPLICATIONS: Viewing SNM as a dynamic network-modulating therapy rather than a static device intervention may reduce unnecessary procedural escalation and improve the consistency of long-term management. The proposed model is intended as an implementable service framework for structured follow-up and reprogramming in patients with suspected LOE.},
}

@article {pmid42230754,
year = {2026},
author = {Bethlehem, L and Bartu, L and Marke, G and Mar, P and Feldman, S and Eggers, J and Ruprecht, C and Britton, GJ and Aggarwala, V and Bongers, G and Li, Z and Yang, N and Hohmann, EL and Mogno, I and Faith, JJ and Grinspan, A},
title = {15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42230754},
issn = {1546-170X},
abstract = {Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) but has undefined composition and poor scalability. In vitro manufactured live biotherapeutic products (LBPs) enable both scalability and defined strain composition but with higher manufacturing complexity, resulting in few LBP clinical trials. Here we show how an accessible platform to produce human-grade LBPs could accelerate LBP development. We provide regulatory documentation and manufacturing protocols to facilitate translating microbiome advances to human trials. With this platform, we conducted the first direct comparison of the same bacterial strains from donor-sourced FMT compared to an in vitro manufactured 15-strain LBP drug product, MTC01, for the treatment of rCDI. In a phase 1b randomized controlled trial, 18 of 20 screened patients met eligibility and were randomized equally to one of four arms: low-dose FMT (n = 4), high-dose FMT (n = 5), low-dose MTC01 (n = 4) or high-dose MTC01 (n = 5), with a 5:1 female:male ratio. The primary outcome of safety was met with 10 adverse events across eight patients, evenly spread across MTC01 (five events) and FMT (five events) recipients and no treatment-related adverse events across all four groups. For secondary outcomes of efficacy and engraftment, rCDI was prevented 8 weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients. Strain engraftment was high and durable for both FMT and MTC01 with a dose effect for the LBP. ClinicalTrials.gov: NCT05911997 .},
}

@article {pmid42231156,
year = {2026},
author = {Yang, Q and Liang, Y and Liu, J and Jia, R and Li, J and Yan, Z},
title = {Fecal microbiota transplantation from Hezuo pigs alleviates intestinal inflammatory injury in Clostridium perfringens type C-infected piglets via modulation gut microbiota and intestinal barrier.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-026-05169-3},
pmid = {42231156},
issn = {1471-2180},
support = {23JRRA1422//Natural Science Foundation of Gansu Province/ ; 32460845//National Natural Science Foundation of China/ ; GSARS10//Pig Industry in Gansu Agriculture Research System/ ; 2023-QN-135//Lanzhou Youth Science and Technology Talent Innovation Project/ ; },
abstract = {Clostridium perfringens type C (CpC)-induced piglet diarrhea is a major challenge in the swine industry. This study aimed to investigate the protective effects of fecal microbiota transplantation (FMT) from Hezuo pigs against intestinal injury in Duroc×Landrace×Yorkshire (DLY) suckling piglets infected with CpC. Piglets were divided into two groups, including CpC-challenged control group and FMT-treatment group, which received fecal suspension from Hezuo pigs prior to infection. Morphological, immunological, microbiomic, and metabolomic analyses were conducted after post-infection. The results demonstrated that FMT significantly alleviated jejunal damage, leading to a significant increase in jejunal villus height and a significant decrease in crypt depth (P < 0.01). The intervention elevated the number of goblet cells (P < 0.05) and upregulated the expression of tight junction protein genes Occludin, ZO-1, Claudin-1 and the anti-inflammatory cytokine IL-10, while significantly reducing the levels of pro-inflammatory cytokines TNF-α and IL-6 (P < 0.05). FMT enriched beneficial genera such as Akkermansia, Rothia, Peptococcus, and Proteocatella, and increased the levels of the sphingolipid metabolite ceramide (d18:1/18:0). Correlation analysis further indicated that these microbiota alterations were positively associated with intestinal barrier repair and anti-inflammatory activity, and were strongly correlated with ceramide (d18:1/18:0) levels. In conclusion, FMT mitigates CpC-induced intestinal injury by modulating the gut microbiota and metabolome, thereby enhancing intestinal barrier integrity and regulating inflammatory responses. This study provides theoretical support and practical insights for the application of FMT as a promising microbiome-based strategy to control CpC-associated intestinal diseases in piglets.},
}

@article {pmid42232158,
year = {2026},
author = {Wang, H and Shao, S and Peng, Y and Xu, W and Zhang, J and Liu, X and Bian, X and Huang, K and Zhang, X},
title = {Pneumococcal Endopeptidase O Attenuates Colitis by Inhibiting the Macrophage-CCL2 Axis and Reshaping Gut Microbiota.},
journal = {Journal of inflammation research},
volume = {19},
number = {},
pages = {601434},
pmid = {42232158},
issn = {1178-7031},
abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by persistent immune activation and gut microbiota dysbiosis, for which current therapies remain limited by incomplete efficacy and substantial adverse effects. This study aimed to investigate the protective effects of pneumococcal endopeptidase O (PepO) on UC and its potential mechanisms of action.

METHODS: The efficacy of PepO was evaluated in a dextran sulfate sodium (DSS)-induced acute colitis mouse model. Clinical phenotypes were assessed using the disease activity index (DAI), colon length, histopathological analysis, and inflammatory cytokine levels. Macrophage infiltration and key inflammatory mediators were analyzed via immunofluorescence, flow cytometry, ELISA, and qPCR. Mechanisms were further validated by macrophage depletion using clodronate liposomes and recombinant CCL2 supplementation. In addition, gut microbiota composition was analyzed via 16S rRNA sequencing, and causality was confirmed through antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) experiments.

RESULTS: PepO administration significantly improved disease activity, colon length, and ameliorated histopathological damage in the mice. Mechanistically, PepO directly inhibited macrophage CCL2 production, reducing macrophage infiltration and the release of pro-inflammatory cytokines in colitis. Additionally, PepO remodelled the gut microbiota and markedly increased the abundance of beneficial bacteria, such as Lactobacillus and Akkermansia. Antibiotic-induced microbiota depletion completely abolished PepO's protective effect, while FMT successfully replicated its protective actions, including suppression of CCL2 expression and macrophage infiltration.

CONCLUSION: This study shows that PepO exerts potent anti-colitic effects through a dual mechanism involving direct inhibition of the macrophage-CCL2 axis and microbiota-dependent enhancement of gut immune homeostasis.},
}

@article {pmid42232317,
year = {2026},
author = {Jakobsen, SS and Kousgaard, SJ and Cold, F and Halkjær, SI and Petersen, AM and Kjeldsen, J and Hansen, JM and Thorlacius-Ussing, O},
title = {The effect of fecal microbiota transplantation on quality of life in patients with chronic pouchitis: a post hoc analysis of the MicroPouch trial.},
journal = {Therapeutic advances in gastroenterology},
volume = {19},
number = {},
pages = {17562848261452497},
pmid = {42232317},
issn = {1756-283X},
abstract = {BACKGROUND: During surgical treatment for ulcerative colitis, an ileal pouch-anal anastomosis is often constructed. Pouchitis, the most common complication after this surgery, substantially reduces patients' quality of life (QoL). In chronic pouchitis, antibiotic treatment often proves ineffective. Fecal microbiota transplantation (FMT) has emerged as a potential treatment for chronic pouchitis.

OBJECTIVES: To determine the effect of FMT on QoL in patients with chronic pouchitis.

DESIGN: An exploratory post hoc analysis of data from the MicroPouch trial. A double-blinded, placebo-controlled study comprising a 4-week intervention period and 12-month follow-up.

METHOD: Thirty patients with chronic pouchitis were randomized 1:1 to receive either FMT or placebo. Treatment was administered by enema once daily for 2 weeks, then every other day for the following 2 weeks. QoL was assessed using three questionnaires-the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Pouch Dysfunction Score (PDS), and the 36-item Short Form Questionnaire (SF-36)-at baseline and at subsequent follow-ups.

RESULTS: At the 30-day follow-up, FMT-treated patients showed a significant decrease in QoL from baseline, measured by the SIBDQ (p = 0.03). Within the FMT group, the PDS did not change significantly from baseline to day 30 (p = 0.36). The placebo group reported higher SF-36 QoL scores at both baseline and day 30 (p = 0.02), although neither group showed significant within-group changes over time.

CONCLUSION: In patients with chronic pouchitis, FMT may temporarily worsen symptoms and reduce QoL, as indicated by three QoL questionnaires showing no improvement or poorer outcomes versus placebo. Trial registration: The study is registered at ClinicalTrials.gov (Trial number NCT04100291), date: 12 September 2019.},
}

@article {pmid42221589,
year = {2026},
author = {Song, D and Gao, H and Wang, T and Wei, Q and Liu, A and Ren, J},
title = {Gut microbiota dysbiosis-induced chronic inflammation as a driver of atherosclerosis: cellular crosstalk and host-microbe interactions.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1789194},
pmid = {42221589},
issn = {2235-2988},
mesh = {*Dysbiosis/complications/microbiology ; Humans ; *Atherosclerosis/etiology/microbiology ; *Gastrointestinal Microbiome ; *Inflammation/microbiology ; Animals ; *Host Microbial Interactions ; Fecal Microbiota Transplantation ; Methylamines/metabolism ; Intestinal Barrier Function ; Fatty Acids, Volatile/metabolism ; },
abstract = {Gut microbiota dysbiosis is increasingly recognized as an upstream contributor to chronic low-grade inflammation and atherosclerosis (AS). Disruption of microbial homeostasis may impair intestinal barrier integrity, increase exposure to pro-inflammatory microbial products and metabolites, and reduce protective metabolites such as short-chain fatty acids (SCFAs), thereby activating innate immune signaling and sustaining vascular inflammation. Current evidence indicates that gut dysbiosis promotes atherosclerosis mainly through three interconnected processes: metabolite imbalance, barrier dysfunction with microbial translocation, and systemic immune reprogramming. Clinical studies have linked gut-derived biomarkers, particularly trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS)-related signals, to atherosclerotic burden and adverse cardiovascular outcomes, while experimental studies using fecal microbiota transplantation, probiotics, antibiotics, and gene-deficient models support a contributory role of the gut-immune-vascular axis. Emerging interventions, including dietary modulation, pharmacological repurposing, and microbiome-targeted therapies, may attenuate gut-derived chronic inflammation and offer new strategies for AS prevention and treatment. However, heterogeneity across studies and the limited causal evidence in humans warrant cautious interpretation. Overall, gut dysbiosis-driven chronic inflammation represents a biologically meaningful and potentially modifiable pathway in atherosclerosis.},
}

*Dysbiosis/complications/microbiology
Humans
*Atherosclerosis/etiology/microbiology
*Gastrointestinal Microbiome
*Inflammation/microbiology
Animals
*Host Microbial Interactions
Fecal Microbiota Transplantation
Methylamines/metabolism
Intestinal Barrier Function
Fatty Acids, Volatile/metabolism

@article {pmid42225253,
year = {2026},
author = {Singh, L and Bhullar, G and Shaik, S and Ganesh, V and Kesani, H and Rai, M},
title = {Gut Feeling: Microbiota as a Hidden Regulator of Hypertension.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101623},
doi = {10.1016/j.tjnut.2026.101623},
pmid = {42225253},
issn = {1541-6100},
abstract = {Emerging evidence identifies the gut microbiota as a key regulator of blood pressure through its role in metabolizing dietary substrates into bioactive compounds that influence vascular, immune, and neurohumoral pathways. This review synthesizes recent mechanistic, preclinical, and clinical evidence linking gut microbial dysbiosis to hypertension, with particular emphasis on nutrition-dependent microbial metabolism and its translational implications. Experimental studies demonstrate that depletion of short-chain fatty acid (SCFA)-producing bacteria and enrichment of pro-inflammatory and trimethylamine-producing taxa contribute to endothelial dysfunction, immune activation, and renin-angiotensin-aldosterone system dysregulation. Fecal microbiota transplantation (FMT) and germ-free animal models provide causal evidence that hypertensive microbiota can directly elevate blood pressure. Human multi-omics and metabolomic studies further show that microbial functional capacity and metabolite production, rather than taxonomic composition alone, are strongly associated with hypertensive phenotypes and therapeutic responsiveness. Importantly, dietary interventions, including high-fiber diets, resistant starch, and the Dietary Approaches to Stop Hypertension (DASH) diet, modulate microbial composition and enhance SCFA production, providing a mechanistic basis for their antihypertensive effects. Microbiota-drug interactions have also emerged as a novel determinant of antihypertensive treatment efficacy. Collectively, these findings support a metabolite-centered framework in which diet-microbiota interactions influence blood pressure regulation. Targeting the gut microbiota through nutritional and microbiome-based strategies represents a promising adjunctive approach for hypertension prevention and personalized management. However, large-scale longitudinal and interventional human studies are needed to establish causality and optimize microbiota-targeted therapies.},
}

@article {pmid42225309,
year = {2026},
author = {Wang, W and Niu, X and Li, S and Cheng, B and Cheng, L and Yang, C and Xu, X and Chang, S and Wang, C and Liu, S},
title = {Efavirenz Mitigates Dyslipidemia and Attenuates Ulcerative Colitis through Gut Microbiota Modulation.},
journal = {ACS infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsinfecdis.6c00330},
pmid = {42225309},
issn = {2373-8227},
abstract = {Antiretroviral therapy (ART) is central to controlling human immunodeficiency virus (HIV) infection, yet it is frequently associated with dyslipidemia, a condition linked to the exacerbation of ulcerative colitis (UC) in people living with HIV (PLWH). The underlying mechanisms of ART-induced dyslipidemia and its contribution to UC progression remain incompletely understood. Here, we demonstrate that efavirenz (EFV), a widely used non-nucleoside reverse transcriptase inhibitor, mitigates ART-induced dyslipidemia and ameliorates UC symptoms. Our in vitro investigations reveal that palmitic acid (PA)-induced inflammation in human normal colorectal mucosal cells (FHCs) is mediated by the activation of the Akt phosphorylation pathway, triggered by the accumulation of 7-dehydrocholesterol (7-DHC), a substrate of 7-dehydrocholesterol reductase (DHCR7). While EFV did not directly modulate this inflammatory cascade in FHCs, in vivo studies using a high-fat diet (HFD)-induced dyslipidemia rat model demonstrated that EFV significantly attenuated elevated lipid levels and improved DHCR7 expression in dextran sulfate sodium (DSS)-induced UC tissues. Notably, fecal microbiota transplantation (FMT) from EFV-treated rats to HFD-fed recipients reduced dyslipidemia and restored DHCR7 expression, thereby suppressing 7-DHC-driven Akt phosphorylation and inflammatory responses in UC tissues. Our findings suggest a mechanism by which EFV mitigates dyslipidemia and UC progression, mediated through the regulation of lipid metabolism and gut microbiota. These findings provide compelling evidence for the potential of EFV to regulate dyslipidemia and associated comorbidities in HIV-infected individuals.},
}

@article {pmid42227044,
year = {2026},
author = {Singh, VK and Gupta, P and Jain, SK and Matreja, PS},
title = {The gut-brain axis in Alzheimer's and Parkinson's diseases: a systematic review of microbiota-derived biomarkers and novel therapeutic approaches.},
journal = {Journal of clinical and experimental neuropsychology},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/13803395.2026.2673084},
pmid = {42227044},
issn = {1744-411X},
abstract = {BACKGROUND: The altered gut microbiota substantially impacts the onset and progression of Alzheimer's disease (AD) and Parkinson's disease (PD), the two most widely studied neurodegenerative conditions. Microbiome-derived metabolites have been increasingly associated with disease onset, progression, and therapeutic targets in neurodegenerative disorders. Exploring the diagnostic and therapeutic implications of gut microbiome-derived biomarkers is critical to advancing our understanding and management of neurodegeneration.

METHODOLOGY: We systematically reviewed both clinical and preclinical studies published from 2010 to 2025. Studies examining gut microbiota composition, microbial-derived metabolites, or therapeutic interventions targeting the gut microbiome were included. Identification of gut microbiome alterations, discovery of microbial or metabolite-based biomarkers, association with disease onset or progression, and/or therapeutic effects on cognitive, neurological, or inflammatory outcomes were evaluated.

RESULT: Short-chain fatty acids(SCFAs) such as butyrate and acetate were found to be noninvasive biomarkers in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and Parkinson's disease (PD). Lower SCFA levels correlated with cognitive decline. Diagnostic accuracy improved when SCFA combinations were used, with AUCs ranging from 0.75 to 0.87. Trimethylamine N-oxide(TMAO) levels showed inconsistent associations, with both elevated and reduced levels linked to disease risk. Therapeutic approaches targeting gut microbiota, including probiotics, prebiotics, dietary changes, and fecal microbiota transplantation, demonstrated cognitive benefits and modulation of gut-brain signaling pathways.

CONCLUSION: Overall, gut-derived biomarkers offer a promising avenue for early diagnosis and novel therapeutic approaches in AD and PD, while acknowledging that evidence in other neurodegenerative diseases remains limited through modulation of the gut-brain axis.},
}

@article {pmid42227494,
year = {2026},
author = {Wang, JM and Wang, RQ and Wang, Y and Gao, XY and Liu, SY and Qi, SW and Hu, GL and Li, DL and Zhang, Y and Xu, XK and Feng, HL},
title = {Exploring the Influence of Circadian Rhythm Disorders in Metabolic Syndrome through Gut Microbiota.},
journal = {Combinatorial chemistry & high throughput screening},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113862073482277260412133043},
pmid = {42227494},
issn = {1875-5402},
abstract = {INTRODUCTION: Metabolic syndrome (MetS) is a chronic metabolic disorder whose global prevalence continues to rise, imposing a significant burden on public health. With the development of round-the-clock societies, shift work has become increasingly commonplace. A growing body of epidemiological evidence indicates that circadian rhythm disruption constitutes a predictable risk factor for MetS; however, the precise mechanisms underlying this relationship remain inadequately understood. This study employed golden hamsters as a model to investigate the effects of circadian rhythm disruption simulated by cyclic light (CL) exposure on MetS.

METHODS: Thirty-three male golden hamsters (7 weeks old, body weight 120-160 g) were randomly assigned to four groups for a 6-week intervention: the Control group (normal light + normal diet, ND), the high-fat diet group (normal light + HFD, to induce a MetS model), the cyclic light group (CL + normal diet, CL), and the CL + HFD group (CL + HFD). Outcome measures included metabolic indicators, hepatic histopathology, and gut microbiota (analyzed via 16S rDNA sequencing).

RESULTS: The stability of the MetS model was assessed through measurements of body weight, fasting blood glucose, and total cholesterol levels. The results indicated that CL exposure may further aggravate metabolic disorders associated with MetS. Furthermore, it was observed that CL exposure intensified MetS-related disturbances in gut microbiota, evidenced by an increase in α-diversity and distinct separation in β-diversity. CL exposure in the MetS model golden hamsters resulted in a reduced abundance of Bacteroidetes and Weissella, alongside an overgrowth of Helicobacter.

DISCUSSION: Circadian rhythm disruption is an independent risk factor for MetS. It further exacerbates metabolic indicators by inducing gut microbiota dysbiosis and promoting the growth of harmful bacteria. Future research should integrate functional metabolomics with faecal microbiota transplantation studies to validate causal mechanisms and explore clinical translational value.

CONCLUSION: Circadian rhythm disruption is an independent risk factor for MetS. It exacerbates the pathological progression of MetS by reducing beneficial bacteria and promoting the growth of harmful bacteria, thereby further damaging its metabolic indicators.},
}

@article {pmid42228606,
year = {2026},
author = {Waghmode, S and Viswanathan, R and Koligudde, V and Umare, P and Lavania, M},
title = {Microbial shifts in early life: the pediatric gut microbiome and its role in health and disease.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2681763},
doi = {10.1080/19490976.2026.2681763},
pmid = {42228606},
issn = {1949-0984},
abstract = {This review explores the pivotal role of the pediatric gut microbiome in shaping early-life development and influencing susceptibility to disease, emphasizing its impact on immune, metabolic, and neurodevelopmental processes. The neonatal period represents a critical window for host-microbiome interactions, beginning at birth when intestinal barrier function is still developing and immune responses remain immature. During this formative stage, rapid microbial colonization and ecological succession are influenced by delivery mode, infant feeding practices, antibiotic exposure, and environmental factors. Beyond bacterial populations, the early-life gut virome composed of bacteriophages and eukaryotic viruses evolves dynamically and contributes to microbial community structure, gene exchange, and immune system maturation. Microbially derived signals and metabolites support the development of mucosal integrity, immune programming, and host microbe equilibrium, with long-term implications for systemic immune function. Breastfeeding fosters the establishment of microbial communities and metabolic profiles associated with immune tolerance, whereas formula feeding and early-life antibiotic use may disrupt normal microbiome development. Alterations in early microbial trajectories have been associated with heightened risk of pediatric conditions, including allergic diseases, obesity, inflammatory bowel disease, and neurodevelopmental disorders. The review further evaluates emerging microbiome-directed strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, considering both their therapeutic promise and current challenges. Collectively, current evidence underscores the early-life gut microbiome as a central determinant of host development and a compelling target for disease prevention strategies.},
}

@article {pmid42229822,
year = {2026},
author = {An, X and Li, C and Chai, Y and Wang, H and Yang, L and Qin, L and Soprun, LA and Gavrilova, NY and Weng, Z and Xu, J and Li, Q and Yang, D and Li, W and Guo, J and Li, Y and Wang, N and Yu, H},
title = {Luteolin rescues high-fat diet-induced hippocampal mitochondrial oxidative stress and cognitive decline by regulating gut microbiota-kynurenine-aryl hydrocarbon receptor axis.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.06.002},
pmid = {42229822},
issn = {1873-4596},
abstract = {High-fat diet (HFD)-induced gut dysbiosis precipitates hippocampal mitochondrial oxidative stress, a pivotal driver of synaptic failure and cognitive decline. However, the molecular conduits linking intestinal microbial shifts to cerebral redox imbalance remain poorly defined, limiting therapeutic strategies. Here, we show that luteolin attenuates HFD-induced cognitive impairment in association with modulation of the gut microbiota-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) axis and improved mitochondrial redox homeostasis. Luteolin treatment ameliorated HFD-induced memory deficits and metabolic abnormalities in mice, effects that were markedly reduced after gut microbiota depletion and were transmissible via fecal microbiota transplantation. Consistent with this pathway, luteolin suppressed HFD-induced expansion of Proteobacteria (e.g., Escherichia coli), diminished intestinal lipopolysaccharide (LPS) leakage, and normalized colonic indoleamine 2,3-dioxygenase 1 (IDO1) expression. Consequently, luteolin reduced peripheral and hippocampal Kyn accumulation, thereby restricting AhR nuclear translocation and preventing the aberrant transcription of AhR-target genes implicated in mitochondrial respiratory chain disruption. Functionally, luteolin restored hippocampal mitochondrial bioenergetics, attenuated pathological reactive oxygen species (ROS) overload, and preserved synaptic long-term potentiation (LTP). The protective efficacy of luteolin against mitochondrial oxidative insult and cognitive decline was phenocopied by AhR inhibition and abrogated by exogenous Kyn supplementation. Collectively, our findings identify the gut Proteobacteria-Kyn-AhR signaling axis as an important contributor to hippocampal mitochondrial oxidative stress in HFD-challenged brains. Luteolin emerges as a promising microbiota-targeted antioxidant intervention that safeguards cognitive function by rectifying this gut-brain redox relay.},
}

@article {pmid42230119,
year = {2026},
author = {Alexander, JL and Mullish, BH and Thomas, L and Weersma, RK and Sokol, H and Roberts, LA and Edwards, LA and Emmanuel, A and Gerasimidis, K and Hall, LJ and Iqbal, TH and Kinross, JM and McIlroy, J and Monaghan, TM and Sergaki, C and Shawcross, DL and Stewart, CJ and Lamb, CA and Williams, HRT and Hansen, R and Hold, G},
title = {Recent advances in our understanding of the gut microbiome: an analysis from the Gut Microbiota for Health Expert Panel of the British Society of Gastroenterology.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2026-338252},
pmid = {42230119},
issn = {1468-3288},
abstract = {At around 10 years ago, at the time of the first publication by the Gut Microbiota for Health Expert Panel of the British Society of Gastroenterology, recognition of the gut microbiome's importance in health and disease was transitioning from fringe interest towards major global pursuit. A decade on, we appraise the considerable progress made in the field, while acknowledging ongoing challenges. Earlier human work characterising the 16S rRNA gene amplicon signature of particular conditions in small cohorts has been superseded by larger, multicentre studies with extensive metadata. Studies increasingly employ shotgun metagenomics and other 'omic' techniques-coupled with refined bioinformatic tools and disease models-to better characterise perturbation in gut microbiome functionality. The arrival of 'gold standard' pipelines for microbiome analysis and increased mechanistic validation of signals are key developments towards more clinically-translatable outcomes. Novel clinical areas where the gut microbiome has relevance have emerged, including early life and the efficacy of certain treatments (including immune checkpoint inhibitors and vaccination). Enthusiasm for 'microbiome diagnostics and treatments' has grown, but barriers to widespread adoption remain. Faecal microbiota transplant (FMT) is established for treating recurrent Clostridioides difficile infection, with donor-derived 'next generation' FMT products licensed for this condition in certain countries. Beyond FMT, other microbial therapeutic techniques-including nutritional, bacteriophage and probiotic therapies-show promise, but have not fulfilled their high expectations yet. Gut microbiome research is now well-established and shows significant translational potential; the future focus will be translational work to drive its utility in clinical diagnostics, prognostics and therapeutics.},
}

@article {pmid42218119,
year = {2026},
author = {Fessler, JL and Olm, MR and Engleman, EG and Sonnenburg, JL},
title = {Integration of donor microbiota following FMT correlates with anti-PD-1 response in melanoma.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-73465-7},
pmid = {42218119},
issn = {2041-1723},
support = {R21CA290426//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Fecal microbiota transplantation (FMT) has shown promise in improving anti-PD-1 therapy in melanoma, but the underlying microbial features remain poorly defined. We performed a strain-resolved metagenomic meta-analysis across three independent FMT plus anti-PD-1 melanoma trials (n = 41). Across cohorts, therapeutic benefit was linked to successful integration of donor microbiota, rather than increased diversity or engraftment of specific species. Responders acquired more donor-derived strains, exhibited greater post-FMT similarity to their donor, and maintained a more stable microbiome. Following FMT, non-responders' microbiomes showed greater taxonomic instability, larger fluctuations in estimated microbial load, and increased abundance of pathogen-associated secretion system genes, whereas responders showed enrichment for microbial functions involved in community-level metabolism and communication. Finally, shifts in tumor-infiltrating immune profiles tracked with clinical outcomes and microbiome changes. Together these findings highlight that distinct patterns of microbiome restructuring, including stable community transitions and altered functional capacity, are associated with anti-PD-1 response following FMT.},
}

@article {pmid42218700,
year = {2026},
author = {Zhang, Y and Wang, Y and Yang, Y and Mei, H and Liu, X and He, Y and Qin, S and Feng, B},
title = {Gut-Liver Axis Failure in Critical Alcohol-Associated Liver Disease: From ICU Secondary Hits to Microbiome-Targeted Therapy.},
journal = {Mediators of inflammation},
volume = {2026},
number = {1},
pages = {e3968719},
doi = {10.1155/mi/3968719},
pmid = {42218700},
issn = {1466-1861},
support = {82460373//National Natural Science Foundation of China/ ; 82560382//National Natural Science Foundation of China/ ; HZ (2025) 312//Zunyi Science and Technology Bureau, China/ ; HZ (2023) 366//Zunyi Science and Technology Bureau, China/ ; HZ (2025) 172//Zunyi Science and Technology Bureau, China/ ; QZYY-2024-137//Guizhou Administration of Traditional Chinese Medicine/ ; gzwkj2024-310//Guizhou Provincial Health Commission/ ; MTyk2024-55//Kweichow Moutai Hospital Research Project/ ; HZ202411//Traditional Chinese Medicine Hospital of Zunyi Medical and Pharmaceutical College/ ; },
mesh = {Humans ; Intensive Care Units ; *Liver Diseases, Alcoholic/therapy/microbiology/metabolism ; *Liver/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; Intestinal Barrier Function ; Fecal Microbiota Transplantation ; Dysbiosis ; },
abstract = {Alcohol-associated liver disease (ALD) can progress to critical illness phenotypes requiring intensive care, including severe alcohol-associated hepatitis, acute decompensation, and alcohol-associated acute-on-chronic liver failure (ACLF). In these patients, short-term outcomes are driven less by the burden of fibrosis alone than by systemic inflammation, immune dysfunction, infection, and multiorgan failure. At the core of this process is gut-liver axis failure, which links alcohol-induced dysbiosis and intestinal barrier disruption to microbial translocation, hepatic innate immune activation, and systemic inflammatory amplification. In the intensive care unit (ICU), secondary hits such as broad-spectrum antibiotics, acid suppression, parenteral nutrition, shock, sedatives or opioids, and mechanical ventilation may further exacerbate these mechanisms and disturb microbial ecology and barrier integrity. Microbiome-targeted therapies (probiotics, postbiotics, and fecal microbiota transplantation) are biologically plausible. However, current evidence is mainly derived from non-ICU or relatively stable ALD populations. Therefore, their use in critically ill patients requires strict safety boundaries, including severe barrier disruption, invasive devices, uncontrolled infections, and profound immune dysfunction. This narrative review synthesizes the pathophysiological continuum from gut barrier failure to systemic inflammation and multiorgan dysfunction in critical ALD, with particular emphasis on ICU-specific secondary hits, safety-aware microbiome modulation, and future phenotype-informed precision strategies.},
}

Humans
Intensive Care Units
*Liver Diseases, Alcoholic/therapy/microbiology/metabolism
*Liver/metabolism
*Gastrointestinal Microbiome/physiology
Animals
Intestinal Barrier Function
Fecal Microbiota Transplantation
Dysbiosis

@article {pmid42218858,
year = {2026},
author = {Sun, Y and Xie, D and Fu, H and He, M and Li, J and Wu, C and Pan, S},
title = {Harpagide alleviates sepsis-induced acute respiratory distress syndrome via gut microbiota modulation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {157},
number = {},
pages = {158329},
doi = {10.1016/j.phymed.2026.158329},
pmid = {42218858},
issn = {1618-095X},
abstract = {BACKGROUND: Sepsis-associated acute respiratory distress syndrome (ARDS) remains a leading cause of mortality in critically ill patients, with limited therapeutic options beyond supportive care. The gut-lung axis is critical in sepsis pathogenesis, yet effective targeting strategies remain scarce. Harpagide (HPG), an iridoid glycoside from Scrophularia ningpoensis, exhibits anti-inflammatory properties, but whether it protects against sepsis-induced ARDS through gut microbiota modulation remains unexplored.

METHODS: Sepsis-induced ARDS was established using the cecal ligation and puncture (CLP) model. Gut microbiota dependency was assessed via antibiotic depletion (ABX) and fecal microbiota transplantation (FMT). Ffar2[-/-] mice were used to verify receptor necessity. Microbial composition and SCFAs were analyzed by 16S rRNA sequencing and GC-MS. Lung signaling was assessed by RNA-seq, Western blot, and RT-qPCR. Plasma SCFAs were quantified in sepsis-induced ARDS patients (n = 12) and healthy controls (n = 12) by LC-MS/MS.

RESULTS: HPG significantly improved survival, attenuated lung injury, and suppressed cytokine storm in septic mice. These effects were abolished by ABX but transferable via FMT, confirming microbiota dependency. HPG enriched acetate-producing taxa, elevating fecal and plasma acetate. Transcriptomic analysis revealed simultaneous suppression of NF-κB signaling and excessive IFN-γ/STAT1 activation. HPG-mediated protection was completely abrogated in Ffar2[-/-] mice, and exogenous sodium acetate recapitulated these effects in a Ffar2-dependent manner. Clinically, plasma acetate was significantly depleted in ARDS patients and correlated with disease severity.

CONCLUSIONS: HPG alleviates sepsis-induced ARDS by reshaping gut microbiota to boost acetate production, which activates FFAR2 to orchestrate immune reprogramming via NF-κB and IFN-γ/STAT1 pathways, offering a novel microbial-metabolic therapeutic strategy.},
}

@article {pmid42219603,
year = {2026},
author = {Coiffard, B and Brodovitch, A and Mège, JL and Bardin, N and Cassir, N},
title = {IgM/IgA-Enriched Immunoglobulins: a Key to Breaking the Cycle of Clostridioides difficile Infection Recurrences in Patients with Hypogammaglobulinemia?.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag291},
pmid = {42219603},
issn = {1537-6613},
abstract = {We present the case of a 57-year-old woman with secondary hypogammaglobulinemia who experienced Clostridioides difficile infection, with repeated recurrences despite transient clinical responses to standard therapies, including repeated fecal microbiota transplantation. Following the replacement of intravenous immunoglobulin supplementation with IgM/IgA-enriched immunoglobulin, no recurrence of CDI was observed during the 24-month follow-up period.},
}

@article {pmid42220281,
year = {2026},
author = {de Bruijn, CMA and Oorthuys, AOJ and Zeevenhooven, J and Davids, M and Levels, JHM and Vlieger, AM and Herrema, H and Nieuwdorp, M and Benninga, MA},
title = {Feasibility and efficacy of fecal microbiota transplantation in adolescents with refractory irritable bowel syndrome: A randomized clinical pilot trial.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpn3.70459},
pmid = {42220281},
issn = {1536-4801},
support = {//Stichting Dioraphte/ ; //For Wis(h)dom Foundation/ ; 09150182010020/ZONMW_/ZonMw/Netherlands ; 015.017.050//Aspasia Premium/ ; },
abstract = {OBJECTIVES: To assess the feasibility and efficacy of fecal microbiota transplantation (FMT) in adolescents (16-21 years) with refractory irritable bowel syndrome (IBS).

METHODS: Randomized controlled pilot trial. Thirty-two patients were included and randomized to receive two allogeneic or autologous FMTs. At baseline and after 6 weeks, two allogeneic or autologous FMTs were administered via a nasoduodenal tube. Feasibility outcomes included dropout rate. Clinical efficacy was evaluated by the proportion of responders (≥50 points reduction in total score of the IBS severity-scoring-system) at 12, 24, and 48 weeks follow-up. Secondary outcomes included health-related quality of life (QoL), depression and anxiety scores, and school/work absenteeism.

RESULTS: One patient (3%) withdrew after randomization, due to lack of effect after the first FMT. Response rates 12 weeks after allogeneic and autologous FMTs were 40% and 38% (p = 0.886). At 24 weeks, significantly more patients responded after allogeneic FMTs (60% vs. 25% autologous, p = 0.048), without significant differences at 48 weeks (60% vs. 50%, p = 0.576). Total QoL score was significantly better after allogeneic than autologous FMTs at 12, 24, and 48 weeks (p = 0.028, p = 0.007, p = 0.011). In the allogeneic FMTs group, school/work absenteeism was 7% at 24 weeks (vs. 41% autologous, p = 0.037).

CONCLUSIONS: Allogeneic FMTs were feasible and resulted in high response rates and better QoL compared to autologous FMTs. These results provide preliminary evidence for the use of allogeneic FMTs in adolescents with refractory IBS.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03074227 (https://clinicaltrials.gov/study/NCT03074227?id=NCT03074227&rank=1).},
}

@article {pmid42220621,
year = {2026},
author = {Kaiser Junior, RL and Piron-Ruiz, L and Tomiatti, RZ and De Castro, MLS and Quadros, LG and Ruiz, MA},
title = {Clinical Remission of Crohn's Disease and Closure of a Rectovaginal Fistula After Autologous Non-Myeloablative Hematopoietic Stem Cell Transplantation.},
journal = {International medical case reports journal},
volume = {19},
number = {},
pages = {550993},
pmid = {42220621},
issn = {1179-142X},
abstract = {BACKGROUND: Crohn's Disease is a chronic, heterogeneous, recurrent and remitting inflammatory bowel disease that can affect any part of the digestive system. To date there is no cure for this disease. Clinical treatment aims to reestablish a balance and avoid crises that are common in an immune-mediated disease that promotes intestinal dysregulation. Anti-inflammatory medications, corticosteroids, immunosuppressants and biologics are part of the therapeutic arsenal for the disease. Obstructions, strictures and intestinal fistulas are complications that require repeat surgery in most patients. Fistulas in the anal or perianal regions are common with rectovaginal fistulas being a serious and complex complication that is difficult to control. Autologous hematopoietic stem cell transplantation can be employed for select patients with severe, refractory autoimmune diseases that have failed to respond adequately to conventional treatments.

CASE PRESENTATION: A 31-year-old Brazilian patient underwent several unsuccessful perianal surgeries for a complex rectovaginal fistula during her twelve years with active Crohn's Disease. Stool elimination was mostly through the vagina as she had rectal stenosis. Consequently, rectal amputation and permanent colostomy implantation were recommended but refused by the patient. Instead, she underwent a non-myeloablative autologous hematopoietic stem cell transplantation. Four years later, she is without active disease, with no manifestation of a rectovaginal fistula. Previous descriptions of rectovaginal fistula closure with hematopoietic stem cell transplantation were not found in a review of the literature.

CONCLUSION: For patients who refuse radical surgery, the presence of a fistula is not a contraindication for hematopoietic stem cell transplantation. The procedure provided progressive improvement not only with apparent cure of the Crohn's disease but with no manifestation of the rectovaginal fistula four years after the transplantation.},
}

@article {pmid42220936,
year = {2026},
author = {Elbeltagi, YM and Abd Rab El Rasool, AO and Elkashlan, AM and Al-Beltagi, M},
title = {Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges.},
journal = {World journal of clinical pediatrics},
volume = {15},
number = {2},
pages = {117274},
pmid = {42220936},
issn = {2219-2808},
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g., aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits.

AIM: To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD.

METHODS: Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I [2] to quantify heterogeneity.

RESULTS: Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I [2] approximately 72%). Risperidone carries a greater metabolic burden (e.g., weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-α autoantibodies.

CONCLUSION: The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.},
}

@article {pmid42221399,
year = {2026},
author = {Al Jnainati, M and Govindarajan, A and Tyagi, S and Iltaf, M and Al Jnainati, J and Ayoub, M and Shadab, HA},
title = {Harnessing Microbiome Therapy to Treat Metabolic Syndrome.},
journal = {AACE endocrinology and diabetes},
volume = {13},
number = {3},
pages = {463-472},
pmid = {42221399},
issn = {3050-9157},
abstract = {BACKGROUND/OBJECTIVE: Metabolic syndrome, a global health crisis marked by insulin resistance, obesity, and dyslipidemia, necessitates novel therapeutic approaches beyond conventional symptom management. Emerging research highlights the gut microbiome as a pivotal modulator of metabolic health, with dysbiosis-characterized by reduced microbial diversity and proinflammatory shifts-implicated in disease pathogenesis. This review synthesizes evidence from preclinical and clinical studies on microbiome-targeted therapies, including fecal microbiota transplantation, designer probiotics, and synbiotics, which aim to restore microbial balance and ameliorate metabolic dysfunction.

CASE REPORT: This review synthesizes evidence from preclinical and clinical studies on microbiome-targeted therapies, including fecal microbiota transplantation, designer probiotics, and synbiotics, which aim to restore microbial balance and ameliorate metabolic dysfunction.

DISCUSSION: Fecal microbiota transplantation transfers beneficial microbiota to enhance insulin sensitivity, while probiotics and synbiotics modulate inflammation, strengthen gut barrier integrity, and stimulate metabolic regulators like glucagon-like peptide-1 and short-chain fatty acids. Mechanistically, these therapies mitigate systemic inflammation, improve glucose/lipid homeostasis, and reduce intestinal permeability linked to endotoxin translocation. Clinical trials report improved glycemic control, lipid profiles, and weight management, underscoring their multitargeted potential. However, challenges such as donor variability, lack of standardized protocols, and long-term safety concerns hinder widespread application. Personalized approaches, informed by machine learning and microbial biomarkers, alongside innovations in Clustered Regularly Interspaced Short Palindromic Repeats-based engineering and encapsulation technologies, may address these limitations.

CONCLUSION: Despite promising outcomes, rigorous large-scale trials and interdisciplinary collaboration are essential to validate efficacy, optimize delivery, and ensure ethical compliance. In conclusion, microbiome therapies represent a paradigm shift in treating metabolic syndrome by targeting root causes, yet translating preclinical success into clinical practice demands further innovation and evidence-based standardization.},
}

@article {pmid42221483,
year = {2026},
author = {Yang, H and Liu, S and Chen, X and Yin, C and Xiao, L and Xu, W and Lv, S and Xie, L and Yin, C},
title = {Gut microbiota-associated immunomodulation contributes to the protective effects of fluvastatin against endometriosis in a mouse model, accompanied by increased Akkermansia muciniphila abundance.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1762444},
pmid = {42221483},
issn = {1664-302X},
abstract = {BACKGROUND: Endometriosis (EMs) is a chronic inflammatory disease characterized by tumor-like growth behavior and limited therapeutic options. Increasing evidence suggests that gut microbiota may contribute to EMs progression by promoting chronic inflammation and immune dysregulation. Fluvastatin, a lipid-lowering agent, exhibits anti-inflammatory, anti-tumor, and immunomodulatory effects and has also been reported to influence microbial homeostasis. However, the relationship among fluvastatin treatment, gut microbiota, and EMs progression remains unclear. This study aimed to investigate this relationship.

MATERIALS AND METHODS: A mouse model of EMs was established by autologous uterine tissue transplantation, followed by oral fluvastatin administration for 3 weeks. Lesion growth, inflammatory responses, and immune characteristics were evaluated by histology, quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry. Gut microbiota involvement was assessed using antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT). Microbial composition was analyzed by metagenomic sequencing. The role of Akkermansia muciniphila was evaluated by direct oral supplementation.

RESULTS: Fluvastatin significantly reduced the volume and mass of ectopic lesions and decreased the mRNA expression of pro-inflammatory cytokines. It was also associated with changes in macrophage polarization-related markers and reduced abnormal activation of splenic immune cells. Antibiotic-induced gut microbiota depletion attenuated the protective effects associated with fluvastatin treatment, whereas FMT from fluvastatin-treated mice partially transferred similar protective changes. Metagenomic analysis revealed that fluvastatin reshaped gut microbiota composition and increased the abundance of Akkermansia muciniphila. Moreover, oral supplementation with Akkermansia muciniphila attenuated EMs progression and was associated with anti-inflammatory and immune-related changes similar to those observed after fluvastatin treatment.

CONCLUSION: These findings suggest that the protective effects associated with fluvastatin treatment are accompanied by changes in gut microbiota composition, including increased abundance of Akkermansia muciniphila. Gut microbiota may contribute to the beneficial effects of fluvastatin in EMs. These results support the potential value of microbiota-informed therapeutic strategies for EMs.},
}

@article {pmid42221532,
year = {2026},
author = {Mishra, AK and Mishra, A and Vikal, A and Singh, H and Y Thajudeen, K and Khan, G and Ahmed, MM},
title = {Fecal microbiota transplant and its usefulness in hepatic disorders: a systematic review.},
journal = {Therapeutic advances in gastroenterology},
volume = {19},
number = {},
pages = {17562848261452504},
pmid = {42221532},
issn = {1756-283X},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapeutic approach aimed at restoring gut microbial balance through the transfer of stool from healthy donors. It has gained significant attention for its role in managing gut dysbiosis-associated disorders, particularly hepatic diseases.

OBJECTIVE: This systematic review evaluated the therapeutic efficacy and clinical potential of FMT in the management of liver-related conditions, including recurrent Clostridium difficile infection (CDI), non-alcoholic fatty liver disease, liver cirrhosis, and hepatic encephalopathy.

DESIGN: A systematic review of existing literature was conducted to assess the clinical outcomes, mechanisms, and challenges associated with FMT in hepatic disorders.

DATA SOURCES AND METHODS: Relevant studies were identified from peer-reviewed scientific databases, focusing on clinical trials, observational studies, and experimental research investigating the role of FMT in gut dysbiosis and liver disease. Data were analyzed to evaluate efficacy, underlying mechanisms, and safety considerations.

RESULTS: FMT demonstrated high efficacy in recurrent CDI, with cure rates exceeding 80%-90%. In hepatic disorders, FMT was associated with improved microbial diversity, enhanced gut barrier integrity, and reduced systemic inflammation, contributing to better liver function and clinical outcomes. However, variability in donor selection, potential safety risks, and regulatory limitations remain significant challenges.

CONCLUSION: FMT represents a promising therapeutic strategy in hepatology, underscoring the critical role of the gut-liver axis. Advances such as synthetic microbiota and personalized microbiome-based therapies may further optimize its safety and efficacy, paving the way for innovative, microbiome-centered interventions in liver disease management.},
}

@article {pmid42214571,
year = {2026},
author = {Chung, HJ and Han, EJ and Kim, DH and Ahn, JS and Choi, YJ},
title = {Gut-derived commensal bacteria attenuate corticosterone-induced depressive-like behavior via regulation of oxidative stress and mitochondrial apoptotic signalling.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108269},
doi = {10.1016/j.phrs.2026.108269},
pmid = {42214571},
issn = {1096-1186},
abstract = {Chronic stress and sustained glucocorticoid exposure disrupt intracellular signaling networks that regulate mitochondrial function and neurotrophic support, thereby increasing vulnerability to depressive disorders. Among these alterations, redox imbalance and mitochondrial dysfunction contribute to impairment of neuronal survival pathways, including TrkB-ERK-CREB-BDNF signaling. However, upstream biological modulators of these stress-responsive processes remain incompletely understood. Here, we investigated whether gut-derived commensal bacteria function as modulators of neuronal signaling under chronic stress conditions. Using a fecal microbiota transplantation (FMT)-based behavioral stratification approach, we identified Intestinimonas butyriciproducens and Parabacteroides merdae as species depleted in mice with increased depressive-like immobility. Functional validation showed that both strains attenuated oxidative stress, reduced intracellular reactive oxygen species, and suppressed mitochondrial apoptotic signaling in neuronal cells, accompanied by restoration of TrkB-ERK-CREB signaling and increased brain-derived neurotrophic factor expression. In a chronic corticosterone model, oral administration of these strains reduced depressive-like behavior and restored hippocampal BDNF levels. Collectively, these findings demonstrate that defined commensal bacteria act as biological modulators of intracellular signaling pathways, including redox balance and mitochondrial function, thereby preserving neurotrophic signaling. This study provides evidence linking specific commensal taxa to modulation of neuronal signaling under chronic stress conditions.},
}

@article {pmid42214609,
year = {2026},
author = {Yuan, S and Lin, L and Liu, J and Lin, Q and Wang, S and Wu, J and Xu, D and Liu, Y and Lee, JY and Qiu, L},
title = {Treadmill exercise attenuates neuroinflammation in APP/PS1 mice via gut microbiota remodeling: Evidence from fecal microbiota transplantation.},
journal = {Life sciences},
volume = {400},
number = {},
pages = {124500},
doi = {10.1016/j.lfs.2026.124500},
pmid = {42214609},
issn = {1879-0631},
abstract = {Alzheimer's disease is associated with gut microbiota dysbiosis, intestinal barrier dysfunction, lipopolysaccharide (LPS) translocation, and neuroinflammation. However, it is unclear whether exercise-induced gut microbiota remodeling causally contributes to the neuroprotective effects of exercise in AD. Herein, APP/PS1 mice underwent 12 weeks of treadmill exercise, and fecal microbiota transplantation (FMT) was used to determine whether exercise-related benefits could be transferred to the recipient mice. Behavioral performance was assessed using the Morris water maze and open-field test. Gut microbial profiles were analyzed by 16S rDNA sequencing. Intestinal barrier integrity was evaluated using histology, AB-PAS staining, and tight-junction protein expression, while plasma and brain LPS levels were measured by enzyme-linked immunosorbent assay. Neuroinflammation was examined with immunofluorescence and Western blotting. It was found that treadmill exercise improved spatial learning, memory, and anxiety-like behavior in APP/PS1 mice. These benefits were partly reproduced in recipients of microbiota from exercised donors. Exercise also restored gut microbial diversity and composition, increased the abundance of taxa including Dubosiella and UBA1819, alleviated colonic injury, enhanced mucus secretion, upregulated ZO-1, Occludin, and Claudin-1, and reduced plasma and brain LPS levels. In parallel, exercise and FMT from exercised donors decreased brain TLR4 expression, attenuated microglial and astrocytic activation, and suppressed TLR4/NF-κB signaling and downstream inflammatory cytokines. These findings indicate that treadmill exercise alleviates neuroinflammation in APP/PS1 mice, at least in part, through gut microbiota remodeling, improved intestinal barrier integrity, and reduced LPS-driven inflammatory signaling.},
}

@article {pmid42215979,
year = {2026},
author = {Li, X and Zhang, X and Yuan, S and Zhang, J},
title = {The gut-lung axis in ARDS: beyond microbial translocation.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-026-03752-w},
pmid = {42215979},
issn = {1465-993X},
support = {82272231//National Natural Science Foundation of China/ ; 82472223//National Natural Science Foundation of China/ ; 2021YFC2500800//National Key Research and Development program from Ministry of Science and Technology of the People's Republic of China/ ; 2025ZD01902600//Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project/ ; 2024ZD0529004//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; },
abstract = {The gut-lung axis has emerged as a pivotal pathway in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Disruption of the intestinal barrier, a common event in critical illness, facilitates the systemic dissemination of live microbiota, their pathogen-associated molecular patterns (PAMPs), and bioactive metabolites. This process critically depends on the integrity of the gut vascular barrier (GVB). The GVB is the endothelial layer underlying the gut epithelium. It serves as the final gatekeeper, restricting microbial products from entering the systemic circulation. Concurrently, intestinal immune cells, such as γδ T cells and innate lymphoid cells (ILCs), migrate to the lungs and amplify the inflammatory cascade. Emerging evidence links regulated cell death, especially pyroptosis, necroptosis, and ferroptosis, to disruption of both gut and lung barriers, fueling a self-amplifying cycle of organ injury. This review synthesizes current evidence on the cellular, molecular, and metabolic mechanisms underlying gut-derived lung injury. Furthermore, we critically evaluate several emerging gut-targeted therapeutic strategies aimed at restoring microbial homeostasis and mitigating ALI/ARDS, including fecal microbiota transplantation (FMT), probiotics, synbiotics, and mesenchymal stem cell (MSC) therapy. Deciphering the gut-lung dialogue holds promise for developing novel treatments for this devastating condition.},
}

@article {pmid42205579,
year = {2026},
author = {Liu, Y and Gong, J and Wang, W and Li, X and Jia, H and Wang, R and Sun, Q and Zhang, R and Zhang, Y and Huang, L},
title = {The effects of filtration and centrifugation on the gut microbiota in fecal microbiota transplantation preparation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1768356},
pmid = {42205579},
issn = {1664-302X},
abstract = {BACKGROUND: The preparation method of fecal microbiota suspensions is crucial for reliable fecal microbiota transplantation research. However, current protocols vary significantly in processing parameters, potentially compromising the comparability of studies. Systematic comparisons of how different preparation techniques affect the microbial community are still lacking.

METHODS: Fresh fecal samples from nine adult volunteers were processed via filtration and centrifugation at various speeds. Microbial viability was assessed via live/dead staining and colony forming unit enumeration. 16S rDNA sequencing was performed to analyze bacterial diversity and taxonomic composition.

RESULTS: The microbial composition and functional potential did not differ between the filtration alone group and the fresh fecal group, and filtration resulted in the lowest bacterial mortality. Mortality increased with increasing centrifugation speed. Centrifugation selectively affected the abundance of some genera (e.g., Delftia and Acinetobacter). High-speed supernatants presented markedly lower OD600 values than low-speed supernatants did, and differential centrifugation visibly reduced the amount of debris.

CONCLUSION: Filtration alone best preserved fecal microbial viability, composition and functional potential. Centrifugation enrichment becomes selective at high speeds. Differential centrifugation offered superior impurity removal. The preparation strategy should be tailored to the research or therapeutic goal.},
}

@article {pmid42206183,
year = {2026},
author = {Wang, Z and Cui, H and Huang, H and Zhang, P and Yin, L and Luo, G and Li, Q and Zhang, Y and Meng, L and Chang, W and Li, X and Yang, X and Ye, J},
title = {Therapeutic effect of Tripterygium hypoglaucum (H. Lév.) Hutch. extract on psoriasis-like skin inflammation correlated with gut microbiota homeostasis in mice.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1822819},
pmid = {42206183},
issn = {1663-9812},
abstract = {BACKGROUND: Tripterygium hypoglaucum (H. Lév.) Hutch. (THH) exerts anti-inflammatory and immunosuppressive effects against psoriasis. However, the extent to which and the mechanisms by which it ameliorates psoriasis-like dermatitis through modulation of the gut microbiota-metabolite axis remain unclear.

METHODS: This study investigated the therapeutic effects and underlying mechanisms of THH in a murine model by employing 16S rRNA gene sequencing, intestinal metabolomic profiling, fecal microbiota transplantation (FMT), and co-housing experiments.

RESULTS: Our results demonstrated that THH treatment significantly decreased PASI scores, alleviated epidermal hyperplasia and skin inflammation, and reversed IMQ-induced gut dysbiosis by restoring the Firmicutes/Bacteroidota ratio and modulating the abundance of beneficial and pathogenic bacteria. Metabolomic analysis revealed that THH normalized multiple metabolic pathways disturbed by IMQ, including arachidonic acid metabolism, sphingolipid metabolism, and primary bile acid biosynthesis. Correlation analyses further revealed significant associations among the altered gut microbiota, key metabolic pathways, and psoriasis-related phenotypic indices. Moreover, FMT from THH-treated mice conferred significant anti-psoriatic efficacy. Similarly, co-housing experiments resulted in the alleviation of skin lesions, reduction of spleen weight, and downregulation of inflammatory cytokines.

CONCLUSION: These findings demonstrate that THH attenuates psoriasis-like dermatitis partly by reshaping gut microbiota composition and regulating key metabolic pathways, supporting a potential gut-targeted therapeutic strategy for psoriasis.},
}

@article {pmid42206375,
year = {2026},
author = {Wang, J and Xu, J and Mai, H and Niu, G and Wu, S and Zhang, X and Zhu, J and Aschner, M and Meng, Q and Chen, R},
title = {Microplastic Exposure Aggravates Cardiomyopathy Under Hemodynamic Stress Through the Gut-Heart Axis.},
journal = {Circulation},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIRCULATIONAHA.126.079820},
pmid = {42206375},
issn = {1524-4539},
abstract = {BACKGROUND: Bisphenol F (BPF) is a common substitute for bisphenol A and the most prevalent bisphenol compound in diverse plastic manufacturing applications. However, the potential toxicity of BPF remains largely unexplored. This study investigates the effects of BPF on the cardiovascular system and intestinal barrier.

METHODS: Germ-free mouse models and fecal microbiota transplantation techniques were used to confirm the role of gut microbiota in BPF-induced cardiovascular injury. Untargeted metabolomics and spatial metabolomics were used to identify the in vivo metabolic products of BPF. Single-cell sequencing was used to identify which cardiac cell types were damaged by BPF exposure.

RESULTS: BPF was detected in 90.5% of 285 human urine samples (median, 1.16 ng/μg creatinine). BPF exposure induced cardiomyocyte hypertrophy, cardiac dysfunction, and intestinal barrier damage, effects contingent on the presence of gut microbiota. Metabolomic analysis identified the microbial conversion of BPF to N-acetylputrescine (NAP). Mechanistically, we found that BPF stimulated intestinal epithelial cells to secrete spermidine/spermine N1-acetyltransferase 1 (Sat1), which catalyzed this conversion. Furthermore, NAP impaired the intestinal barrier by disrupting the Golgi-mitochondria axis and caused cardiac hypertrophy by activating the p53 pathway and inhibiting glycolysis in cardiomyocytes. Supplementation with Akkermansia muciniphila or its metabolite tryptophol mitigated BPF-induced cardiac and intestinal injuries by downregulating the Sat1-NAP axis. Clinical analysis further showed elevated serum NAP levels in patients with inflammatory bowel disease, positively correlating with cardiac injury markers.

CONCLUSIONS: BPF disrupts intestinal barrier function through microbial metabolism involving the tryptophol/Sat1 pathway, leading to NAP production. NAP damages intestinal organelles and enters circulation, inducing cardiac p53 activation and hypertrophy. This study delineates a novel gut microbiota-Sat1-NAP pathway underlying BPF-induced cardiotoxicity, offering new insights for risk assessment and therapeutic intervention.},
}

@article {pmid42208345,
year = {2026},
author = {Lauriola, M and Dejongh, S and Steigert, S and Zadora, W and Valkenburg, S and Augustijns, P and Glorieux, G and Oswald, S and Farré, R and Meijers, B},
title = {Kidney dysfunction regulates gut transporters.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {200},
number = {},
pages = {119581},
doi = {10.1016/j.biopha.2026.119581},
pmid = {42208345},
issn = {1950-6007},
abstract = {BACKGROUND: The gut-kidney axis is crucial in chronic kidney disease (CKD). As kidney function declines, uremic toxins accumulate in plasma, and gut dysbiosis, oxidative stress, and inflammation arise, potentially affecting the expression of proteins involved in absorption, distribution, metabolism, and excretion (ADME). We aimed to determine the colonic expression of ADME proteins in CKD and explore modulatory mechanisms.

METHODS: RNA and protein expression of key gut transporters, enzymes and receptors were determined in colon biopsies from 17 patients with CKD and 12 healthy volunteers using RNA sequencing and targeted mass spectrometry. In parallel, we induced CKD in rats by 5/6th nephrectomy, and we administered an antibiotic cocktail to assess differences when depleting the gut microbiome. Caco-2 cells exposed to human serum or fecal water derived from CKD patients were used to elucidate modulatory mechanisms.

RESULTS: CKD downregulated the colon efflux transporter proteins P-gp (apical), MRP3 (basolateral) and BCRP (apical) (BCRP only in patients not undergoing hemodialysis). P-gp downregulation was mediated by aromatic gut microbiome-derived uremic toxins in patients, consistently with in vitro observation that P-gp was downregulated in Caco-2 cells exposed to CKD serum. In CKD rats' colon, Mdr1a was downregulated, and Bcrp was upregulated only when antibiotics were administered, indicating the gut microbiome influences P-gp and BCRP in CKD.

CONCLUSIONS: We confirmed kidney-gut crosstalk, highlighting how uremic environment and gut dysbiosis consequent to CKD impact gut transport physiology. P-gp and BCRP can be downregulated via gut microbiome metabolites, thus shedding light on the importance of therapies targeting microbial activity.},
}

@article {pmid42211136,
year = {2026},
author = {Rashidi, A and Minot, SS and Lee, SJ and Hill, GR and Podlesny, D},
title = {Cohesive modules of engraftment in fecal microbiota transplantation.},
journal = {iScience},
volume = {29},
number = {6},
pages = {116025},
pmid = {42211136},
issn = {2589-0042},
abstract = {While single-strain probiotics fail to address community-level microbiota injuries in dysbiosis-related conditions and fecal microbiota transplantation (FMT) produces unpredictable communities, a middle-ground approach has emerged. This approach involves using small consortia of species, combining the precision of single-strain probiotics and the holistic approach intrinsic to FMT. The species selection in this oligomicrobial strategy is typically proprietary or based on studies linking single species to disease or health. To advance this approach, we developed the concept of cohesive modules of engraftment (CME) and a workflow for their identification from FMT trials. CMEs represent small donor microbiota subsets that engraft as units (modularity), while maintaining their original composition (cohesiveness). In benchmarking, we identified >200 highly cohesive CMEs (2-5 species) in 5 FMT trials and found evidence for cross feeding as a mechanism for CME integrity. Due to their predictable post-treatment compositions, CMEs deserve investigation as potential ingredients of future therapeutic microbial consortia.},
}

@article {pmid42211453,
year = {2026},
author = {Fei, Y and Mao, P and Fan, B},
title = {Mapping the gut microbiota-diabetic peripheral neuropathy research landscape: a bibliometric analysis of emerging trends and translational frontiers.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1815280},
pmid = {42211453},
issn = {1664-2392},
mesh = {Animals ; Humans ; *Bibliometrics ; *Diabetic Neuropathies/microbiology/therapy ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; *Translational Research, Biomedical/trends ; },
abstract = {BACKGROUND: Diabetic peripheral neuropathy (DPN) constitutes the most prevalent chronic complication of diabetes mellitus, affecting approximately 50% of patients throughout their disease course. Accumulating evidence indicates that gut microbiota (GM) dysbiosis plays a pivotal role in DPN pathogenesis via the gut-brain axis. However, a comprehensive bibliometric analysis delineating the intellectual landscape and evolutionary trajectory of this rapidly advancing research domain remains absent.

METHODS: Publications pertaining to gut microbiota and DPN were systematically retrieved from the Web of Science, PubMed, and Scopus databases (spanning 2010-2025). CiteSpace 6.4.R1 was employed to perform co-occurrence, clustering, timeline, burst detection, and co-citation analyzes, thereby visualizing the field's intellectual structure and developmental trends.

RESULTS: A total of 133 publications met the inclusion criteria, exhibiting exponential growth after 2018 with an average annual increase of 35.7%. Keyword analysis identified core research clusters centered on GM, neuropathic pain, the gut-brain axis, and therapeutic interventions such as fecal microbiota transplantation (FMT), traditional Chinese medicine, and causal inference methodologies like Mendelian randomization. Burst detection analysis revealed a temporal shift from foundational concepts (e.g., "oxidative stress", "inflammation") toward interventional strategies (e.g., "fecal microbiota transplantation", "traditional Chinese medicine") and causal inference approaches (e.g., "Mendelian randomization"). Co-citation analysis highlighted seminal contributions, including clinical trials demonstrating FMT efficacy and animal studies elucidating the role of microbial metabolites such as butyrate.

CONCLUSION: This study presents the inaugural bibliometric analysis of the GM-DPN research field. The domain is transitioning from establishing associative links to elucidating causal mechanisms and evaluating targeted interventions. Keyword trend analysis underscores a convergence toward a multi-mechanistic gut-brain axis model. Future research priorities derived from the literature encompass clinical translation, multi-omics integration, and personalized therapeutic strategies.},
}

Animals
Humans
*Bibliometrics
*Diabetic Neuropathies/microbiology/therapy
*Dysbiosis/microbiology
*Gastrointestinal Microbiome/physiology
*Translational Research, Biomedical/trends

@article {pmid42213471,
year = {2026},
author = {George, M and Negi, L and Maan, M},
title = {A Gutsy Move? Microbiome Reset With Fecal Microbiota Transplant Brings Remarkable Turnaround in Severe Alcohol-Associated Hepatitis: A Case Report.},
journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates},
volume = {49},
number = {3},
pages = {163-178},
pmid = {42213471},
issn = {1538-9766},
}

@article {pmid42214222,
year = {2026},
author = {Qiao, Y and Zhang, X and Wu, F and Wang, Y and Wu, Y and Zhang, Y and Cheng, W and Bu, F and Miao, Y and Wang, Y and Huo, X and Wang, J and Ma, X},
title = {Wedelolactone alleviates rheumatoid arthritis by gut microbiota-dependent immunomodulation and p53-mediated inhibition of fibroblast-like synoviocytes.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {157},
number = {},
pages = {158297},
doi = {10.1016/j.phymed.2026.158297},
pmid = {42214222},
issn = {1618-095X},
abstract = {BACKGROUND: Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and a parallel dysbiosis of the gut microbiota. Wedelolactone (WL), a natural bioactive compound, exhibits potent anti-inflammatory and immunomodulatory activities; however, its therapeutic potential in RA is unknown.

PURPOSE: This study aimed to evaluate the potential effect of WL on RA and explore its underlying mechanism.

METHODS: The anti-arthritic activity of WL was assessed in wild-type and antibiotic‑treated (ABX) collagen‑induced arthritis (CIA) mice in vivo and in human rheumatoid-arthritis synovial fibroblasts (MH7A) cells and murine rheumatoid-arthritis fibroblast-like synoviocytes (RA-FLS) cells in vitro. Additionally, fecal microbiota transplantation (FMT), 16S rDNA sequencing, intestinal barrier integrity assays, splenic and colonic Th17/Treg analyses and targeted metabolomics of short-chain fatty acids (SCFAs) were performed to clarify its microbiota-directed actions. Finally, RNA-seq coupled with chemical inhibition and genetic knockdown with siRNA were employed to explore its effect on the hyperproliferation of synoviocytes.

RESULTS: WL attenuated RA symptoms in CIA mice as evidenced by delayed disease onset, decreased joint swelling, less bone invasion and lower cumulative incidence. WL also reduced the Th17/Treg cell ratio in the spleen and colon and improved the intestinal barrier by inhibiting colonic inflammation and up-regulating tight junction proteins ZO-1 and Occludin. Concomitantly, WL reversed the RA-induced dysbiosis of gut microbiota and markedly elevated SCFAs levels, thereby restoring intestinal barrier integrity and re-establishing Th17/Treg homeostasis. FMT significantly ameliorated arthritis, further verifying the role of the gut microbiota-joint axis in the anti-arthritic effect of WL. However, FMT only partially mimicked the efficacy of WL, which was comparable to that of WL in ABX mice, indicating an additional microbiota-independent pathway. Additionally, WL directly inhibited the proliferation and migration of both MH7A and RA-FLS cells and induced G0/G1 cell cycle arrest. Transcriptomic profiling revealed that WL up-regulated p53-pathway genes including MDM2 and CDKN1A. Subsequently, pharmacologic blockade and genetic knockdown of the p53 axis abolished WL-induced decreases in cell viability and EdU positive cells and reversed the up-regulation expression of CDKN1A and HMOX1. Mechanistically, WL directly bound to p53, disrupted the p53-MDM2 interaction, suppressed p53 ubiquitination and proteasomal degradation, thereby stabilizing and upregulating p53 expression.

CONCLUSION: WL mitigated CIA in mice by modulating gut microbiota-SCFAs-Th17/Treg axis and inhibiting proliferation of RA-FLS via p53 pathway. The findings provide the pre-clinical foundation for the development of WL as an anti-RA agent.},
}

@article {pmid42214386,
year = {2026},
author = {Sun, H and Dulencin, A and Kirn, TJ and Vo, J and Liachko, I and Rao, D and Manzano-Santana, J and Patel, E and Looi, C and Horton, DB and Barrett, E and Weidner, M and Bachmann, G and Panettieri, RA and Connor, BA and Rogova, M and Nagy-Szakal, D and Couto-Rodriguez, M and Kotwal, S and Wu, Q and Simon, J and Blaser, MJ and Dominguez Bello, MG},
title = {Autologous fecal microbiota transplantation restores the infant gut microbiome and metabolome after antibiotics: a case report.},
journal = {mBio},
volume = {},
number = {},
pages = {e0071126},
doi = {10.1128/mbio.00711-26},
pmid = {42214386},
issn = {2150-7511},
abstract = {UNLABELLED: Antibiotic exposure during infancy disrupts gut microbiome assembly during a critical developmental window. Strategies to restore these ecosystems remain limited. In the REPAIR trial (NCT06609980), eight infants were followed longitudinally; two received amoxicillin for otitis media, and one subsequently underwent autologous fecal microbiota transplantation (aFMT) using stool collected prior to antibiotic exposure. Shotgun metagenomics, Hi-C-assisted resistome profiling, and untargeted metabolomics were performed on samples collected before and after antibiotics. Amoxicillin treatment was associated with displacement of community structure, enrichment of antibiotic resistance genes (ARGs), and altered fecal metabolites, including short-chain fatty acids, bile acids, acylcarnitines, bilirubin derivatives, tricarboxylic acid (TCA) cycle metabolites, and amino acids. In the non-restored infant, microbiota composition and ARG profiles remained persistently altered during follow-up, accompanied by sustained metabolic divergence. In contrast, the aFMT-treated infant demonstrated convergence toward pre-antibiotic community structure, directional restructuring of ARG carriers -including reduction of β-lactam and tetracycline resistance genes- and metabolite profiles trending toward the pre-antibiotic baseline across analytical platforms. Although limited to a case-based comparison, these findings provide integrated ecological and functional evidence that aFMT may promote recovery following antibiotic perturbation during early-life microbiome development and support the rationale for larger controlled clinical trials.

IMPORTANCE: Antibiotic exposure in early life disrupts the developing gut microbiome during a critical window of host-microbe interaction. However, the extent to which these disturbances resolve naturally, or can be actively reversed, remains unclear. In this study, we use longitudinal sampling in infants to examine microbiome recovery following antibiotics, with and without autologous fecal microbiota transplantation (aFMT). We show that antibiotic exposure leads to coordinated disruptions in microbial composition, antibiotic resistance genes, and metabolic profiles. While partial recovery spontaneously occurs over time, faster and more extensive restoration toward the pre-antibiotic state is observed following aFMT. These findings provide insight into the ecological dynamics of microbiome reassembly in early life and highlight the potential of using controlled perturbations to understand microbiome resilience.

CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT06609980.},
}

@article {pmid41963962,
year = {2026},
author = {Li, Y and Wu, H and Yang, J and Weedor, JG and Ding, H and Cui, W and Cui, B and He, Z and Zhang, W and Xing, Y and Zeng, F and Huang, X and Zheng, K and Shen, Y and Yu, Y and Pan, W and Yang, X},
title = {Clostridium butyricum ameliorates Toxoplasma gondii-induced neuropsychiatric disorders by attenuating glial-mediated synaptic pruning via the gut-brain axis.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41963962},
issn = {1742-2094},
support = {Nos. 202310313083Y//the Training Programs of innovation and Entrepreneurship for College Students in Jiangsu Province/ ; Nos. X202510313020//the Training Programs of innovation and Entrepreneurship for College Students in Jiangsu Province/ ; Nos. X202510313017//the Training Programs of innovation and Entrepreneurship for College Students in Jiangsu Province/ ; No. JC20250007//the Faculty Development Grant of Basic Medical Sciences in Xuzhou Medical University/ ; Nos. 82372283//the National Natural Science Foundation of China/ ; No. QL-YB022//the XZHMU-QL Joint Research Fund/ ; No. 2022M710120//China Postdoctoral Science Foundation/ ; },
abstract = {UNLABELLED: Gut microbiota dysbiosis contributes to Toxoplasma gondii (T. gondii)-induced neuropsychiatric disorders (TNDs); however, the underlying mechanisms remain largely elusive. Here, we identified the critical role of butyrate-producing bacteria in TNDs in mice. Decreased abundance of butyrate-producing bacteria was consistently observed in patients with Alzheimer’s disease and T. gondii-infected mice. Dietary supplementation with Clostridium butyricum (C. butyricum), a gut commensal butyrate-producing bacterium, reversed gut microbiota dysbiosis, ameliorated intestinal barrier disruption and inflammation, and reduced endotoxemia. Coincidentally, C. butyricum administration suppressed microglial and astrocytic activation, rescued synaptic ultrastructure damage and synaptic loss, thus alleviating cognitive impairment and anxiety/depression-like behaviors. Mechanistically, C. butyricum treatment mitigated the abnormal synaptic pruning mediated by glial cells and C1q to prevent the neuropathology induced by T. gondii infection. Importantly, fecal microbiota transplantation from C. butyricum-supplemented mice into antibiotic-treated recipients recapitulated the therapeutic effects on gut and brain pathology observed in infected mice. Together, our findings suggest that C. butyricum ameliorates TNDs by modulating glial cell-mediated abnormal synaptic pruning via the gut-brain axis, highlighting the therapeutic potential efficacy of butyrate-producing bacteria against TNDs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03761-y.},
}

@article {pmid42201625,
year = {2026},
author = {Akram, F and Zainab, S and Shabbir, I and Haq, IU},
title = {Gut microbiota and cancer immunotherapy: from dysbiosis to personalized immune checkpoint blockade optimization.},
journal = {Folia microbiologica},
volume = {},
number = {},
pages = {},
pmid = {42201625},
issn = {1874-9356},
abstract = {Cancer has become one of the most prominent causes of death worldwide due to its increasing mortality rate. Immune checkpoint blockade therapy is an effective regimen for tumor control. Still, it faces challenges, including primary resistance and interindividual variations, thereby directing the field towards a new era of immunotherapy adjuncts. Recent studies have shown that the microbiota of cancer patients influences the outcomes of ICB (immune checkpoint blockade) therapy through microbiome-immune system crosstalk. Homeostatic commensal microbial consortia aid in combating tumors by enhancing immunity, whereas dysbiotic microbes facilitate cancer development by mediating immunosuppression. Microbiota modulation via microbiome-targeted interventions, including fecal microbiota transplantation or washed microbiota transplantation from responders, biotic supplements, and dietary modifications, can convert primary resistance to durable responses and thus augment immunotherapy responsiveness in cancer treatment. This review discusses the dual nature of microbiota in mediating the development and treatment of cancer, its crucial role in shaping ICB therapy responsiveness, and the identification of microbial biomarkers into a refined Discovery-Validation-Clinical (DVC) pipeline linked to multi-omics profiling and personalized microbiome-modulation interventions for ICB therapy optimization. In addition, it presents the translational clinical decision framework that highlights patient stratification, intervention timing, and implementation barriers to support clinical translation. Ultimately, the gut microbiome emerges as a "force multiplier" of cancer ICB therapy, thereby enabling microbiome-guided precision oncology and strengthening a roadmap toward personalized cancer care.},
}

@article {pmid42202865,
year = {2026},
author = {Hoel, ME and Gimenez, AR and Elbe, A and Horecka, K and Alvarez, E and Lashnits, E},
title = {Oral fecal microbial transplant for parvovirus in the outpatient setting: a randomized controlled trial to evaluate a practical and low-cost intervention.},
journal = {Journal of the American Veterinary Medical Association},
volume = {},
number = {},
pages = {1-7},
doi = {10.2460/javma.26.01.0051},
pmid = {42202865},
issn = {1943-569X},
abstract = {OBJECTIVE: To evaluate commercially available oral capsules providing fecal microbial transplant (FMT) as a practical option for adjunctive treatment of canine parvovirus (CPV) in an outpatient setting. We hypothesized that treatment with FMT capsules would improve survival and hasten resolution of clinical signs compared to placebo.

METHODS: This blinded, randomized controlled trial evaluated oral FMT capsules in shelter dogs with CPV treated with an outpatient protocol (September 2022 to August 2024). Eligible dogs were randomized to receive adjunctive FMT or placebo, with 3 dosing regimens assessed. The primary outcome was time to recovery; secondary outcomes included survival, escalation to ICU, and resolution of clinical signs.

RESULTS: 101 dogs were enrolled, of which 52 were in the control group and 49 received FMT. Dogs that survived without escalation to ICU-level care in both the control (n = 42) and FMT groups (32) had a median duration to recovery of 5 days (P = .872). There was a 94% (49 of 52) survival rate in the control group compared to 82% (40 of 49) for the group receiving FMT (P = .051); there was no significant difference in survival between groups when controlling for age or weight (OR, 3.18; 95% CI, 0.74 to 17.28; P = .139).

CONCLUSIONS: There was no evidence that oral FMT capsules hastened recovery or improved short-term survival rate in an outpatient setting. Future work is needed to determine whether oral FMT has negative effects in dogs with CPV.

CLINICAL RELEVANCE: This study provides evidence that oral FMT treatment may not be helpful in the outpatient treatment of CPV.},
}

@article {pmid42203970,
year = {2026},
author = {Ning, K and Chen, Y and Yang, X and Dou, X and Liu, S and Wang, DE and Niu, Y and Xu, H},
title = {Gut microbiota alteration contributes to bone marrow mesenchymal stem cells connexin43 response to high-fat diet induced obesity in mice.},
journal = {International journal of obesity (2005)},
volume = {},
number = {},
pages = {},
pmid = {42203970},
issn = {1476-5497},
abstract = {BACKGROUND/ OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) contribute to controlling adipose tissue homeostasis and may be a potential target for obesity therapy. Since lack of connexin43(Cx43) in mesenchymal stem cells (MSCs) is known to combat high-fat diet (HFD)-induced adiposity. Also, HFD is a well-known risk factor for gut microbiota dysbiosis. Here we attempt to address the interaction between HFD, gut microbiota, and Cx43 deficiency in BMSCs during the development of obesity.

METHODS: BMSC-specific Cx43 knockout (Prrx1-Cre;Cx43[flox/flox](cKO)) and control littermate (Cx43[flox/flox](flox))mice were fed a regular chow diet or a HFD for 8 weeks. Cecal microbiome composition was assessed by 16S ribosomal RNA (rRNA) sequencing, and further analyzing correlation between gut microbiota and obesogenic parameters. Moreover, transplantation fecal microbiota was used to probe the salutary effect of BMSC Cx43.

RESULTS: HFD fed cKO mice notably altered cecal microbiome composition as proved by a distinctively clustered separation from flox mice. Concomitantly, Allobaculum induced by HFD was strongly correlated positively with body weight, glucose intolerance, and adipose mass. The recipients with gut microbiota from cKO mice displayed anti-obesity phenotype as the donors.

CONCLUSIONS: Gut microbiota alteration may be one main reason for the salutary effect of BMSC Cx43 knockout on body adiposity.},
}

@article {pmid42204443,
year = {2026},
author = {Henriksen, IW and Hansen, CHF and Koch, J and Sørensen, DB and Nielsen, DS and Bartholdy, C and Hansen, AK},
title = {A Refined Method for Fecal Microbiota Transplantation Using Nutella.},
journal = {Clinical and translational science},
volume = {19},
number = {6},
pages = {e70576},
doi = {10.1111/cts.70576},
pmid = {42204443},
issn = {1752-8062},
mesh = {Animals ; *Fecal Microbiota Transplantation/methods/adverse effects/instrumentation ; Mice, Inbred BALB C ; Mice ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome/genetics ; Administration, Oral ; Female ; },
abstract = {Fecal microbiota transplantation (FMT) in mice is an evolving research field, often employing oral gavage, which can be stressful and harmful for the animals and time-consuming for technicians. Voluntary intake methods, such as delivery in Nutella, have successfully been used for drug administration in mice and may likewise be a promising tool to refine traditional FMT techniques. Nutella-based FMT may improve animal welfare, reduce workload, and enhance animal safety without compromising microbiota engraftment rates. This study compared microbiota engraftment after mouse-to-mouse FMT in antibiotic-treated BALB/c mice using three methods: oral gavage, pipette delivery, and voluntary intake of a Nutella-inoculum mixture. Feces collected before and after FMT were analyzed using GridION Nanopore 16S rRNA gene amplicon sequencing. Nutella-based FMT showed similar engraftment rates as traditional methods i.e., oral gavage and pipette delivery. Oral gavage delivery resulted in greater variability and divergence from the donor composition compared to pipette delivery. Notably, the oral gavage group had the highest number of genera differing from the donor. Single-dose FMT restored microbial diversity in one study, while it was less effective in another, suggesting to add a second dose of FMT. Nutella-based FMT appears to be an efficient, reproducible, and less stressful alternative to forced-feeding methods, warranting further exploration.},
}

Animals
*Fecal Microbiota Transplantation/methods/adverse effects/instrumentation
Mice, Inbred BALB C
Mice
Feces/microbiology
RNA, Ribosomal, 16S/genetics
*Gastrointestinal Microbiome/genetics
Administration, Oral
Female

@article {pmid42204557,
year = {2026},
author = {Preetam, S and Bora, J and Porna Dutta, S and Talukdar, N and Rustagi, S and Thapliyal, S and Malik, S and Choudhary, N and Kumar, D and Kondaveeti, SB},
title = {Role of gut microbiota in cancer modulation: molecular mechanisms and emerging therapeutic strategies.},
journal = {Infectious agents and cancer},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13027-026-00767-2},
pmid = {42204557},
issn = {1750-9378},
abstract = {The gut microbiota exerts profound effects on host physiology, immunity, and disease susceptibility, with growing evidence implicating its role in cancer initiation, progression, and therapy response. Dysbiosis and microbial-derived metabolites contribute to oncogenesis by modulating epithelial signalling, immune regulation, and systemic inflammation. This review synthesises current knowledge on the crosstalk between the gut microbiome and cancer, spanning molecular mechanisms, site-specific malignancies, and treatment outcomes. We discuss how microbial pathways, including NF-κB, STAT3, Wnt/β-catenin, and inflammasome activation, shape tumour biology, and how microbiota profiles correlate with cancer risk and progression in colorectal, gastric, liver, breast, gynaecological, and pulmonary cancers. Furthermore, we highlight the microbiome's impact on responses to chemotherapy, radiotherapy, and immunotherapy. Finally, we evaluate therapeutic strategies targeting the microbiota, from conventional dietary and probiotic interventions to cutting-edge approaches such as faecal microbiota transplantation, engineered bacterial strains, and microbiome-based biomarkers. Understanding these complex interactions offers novel opportunities to integrate microbiome science into precision oncology.},
}

@article {pmid42204645,
year = {2026},
author = {Zhao, N and Wu, L and Peng, S and Yang, H and Song, Y and Zhang, Y and Ding, L},
title = {Decoding the microbiome-immune crosstalk in cancer: from mechanisms to therapeutic translation.},
journal = {Biomarker research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40364-026-00930-2},
pmid = {42204645},
issn = {2050-7771},
support = {82303235//National Natural Science Foundation of China/ ; 2025SF-YBXM-358//Key Research and Development Projects of Shaanxi Province/ ; 2025JC-YBQN-1236//Natural Science Basic Research Program of Shaanxi Province/ ; NUHSRO/2023/005/Startup/3//NUS STARTUP grant/ ; MOH-OFIRG24jan-0001, MOH-OFIRG23jul-0007 and MOH-OFIRG21nov-0007//NUS-NJU Research Collaboration Fund 2025, OF-IRG grant from National Medical Research Council/ ; NRF, CRP28-2022RS-0001//CRP grant from National Research Foundation/ ; },
abstract = {The gut microbiome plays a critical role in shaping host immunity and profoundly affects the efficacy of cancer immunotherapy. Accumulating evidence suggests that interventions designed to alter the microbial community, including fecal microbiota transplantation, probiotics, and engineered bacteria, can reprogram the tumor-immune microenvironment and enhance clinical efficacy. This Review provides a comprehensive overview of the molecular and cellular mechanisms through which the gut microbiota influences antitumor immunity, and it highlights recent clinical studies evaluating these interventions. We further examine inherent challenges, including inter-individual variability in microbial composition, difficulties in achieving stable and durable colonization, technical barriers in delivery, and potential safety concerns associated with immune activation or off-target effects. Finally, we discuss future directions for translating microbiome-targeted therapies into oncology, emphasizing the need for mechanistic insight, standardized protocols, rigorous evaluation, and integration with precision immunotherapy strategies to optimize therapeutic outcomes.},
}

@article {pmid42205476,
year = {2026},
author = {Pollicardo, C and Gotta, F and Bottino, P and Vay, D and Pizzo, V and Scaglione, S and Pontarollo, G and Novi, M and Boatti, L and Mignone, F and Melioli, G and Rapallo, F and Rocchetti, A},
title = {Defining reference values for the gut microbiota in a Southern European population.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1766733},
pmid = {42205476},
issn = {2235-2988},
mesh = {Humans ; Reference Values ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation & purification ; High-Throughput Nucleotide Sequencing ; Fecal Microbiota Transplantation ; Europe ; Sequence Analysis, DNA ; Male ; Female ; DNA, Bacterial/genetics ; European People ; Adult ; },
abstract = {INTRODUCTION: The clinical implementation of gut microbiota analysis requires the definition of reliable reference values derived from standardized and certified methodologies applied to a population representative of the intended clinical setting.

METHODS: In this study, 250 fecal samples were analyzed using a CE-certified 16S rRNA bacterial profiling assay for taxonomic characterization across multiple bacterial levels. Sequencing reads were quality-filtered and aligned against the RDP database (release 11, update 5); only sequences with ≥80% alignment coverage and ≥97% similarity were retained.

RESULTS: The resulting taxonomic distributions were first compared with data previously obtained from a similar population, revealing only minor differences. As an additional validation, comparative analyses were performed with data from a clinical study on fecal microbiota transplantation (FMT). Donor profiles were highly consistent with those obtained in the present study, whereas pre-transplant samples showed marked deviations from the reference ranges; post-transplant profiles progressively converged toward them.

DISCUSSION: Although the limited sample size precludes accurate assessment of rare taxa (<0.1% relative abundance), the use of a single Next-Generation Sequencing (NGS) platform and the focus on a Southern European population characterized by the Mediterranean diet allowed the establishment of the first set of gut microbiota reference values derived from a certified in-vitro diagnostic workflow. These data represent an essential step toward the integration of gut microbiota testing into clinical laboratory practice, enabling standardized interpretation of microbiota imbalance and supporting targeted medical interventions aimed at restoring microbial equilibrium.},
}

Humans
Reference Values
Feces/microbiology
*Gastrointestinal Microbiome/genetics
RNA, Ribosomal, 16S/genetics
*Bacteria/classification/genetics/isolation & purification
High-Throughput Nucleotide Sequencing
Fecal Microbiota Transplantation
Europe
Sequence Analysis, DNA
Male
Female
DNA, Bacterial/genetics
European People
Adult

@article {pmid42020750,
year = {2026},
author = {Grieshop, MP and Behr, AA and Bowden, S and Lin, JD and Molari, M and Reynolds, GZ and Brooks, EF and Doyle, B and Moore, AA and Rodriguez-Nava, G and Salinas, JL and Banaei, N and Bhatt, AS},
title = {Transposable elements are driving rapid adaptation of Enterococcus faecium.},
journal = {Nature},
volume = {653},
number = {8116},
pages = {1139-1147},
pmid = {42020750},
issn = {1476-4687},
mesh = {*Enterococcus faecium/genetics/pathogenicity/isolation & purification ; *DNA Transposable Elements/genetics ; Humans ; Genome, Bacterial/genetics ; *Adaptation, Physiological/genetics ; Metagenome/genetics ; Promoter Regions, Genetic/genetics ; Feces/microbiology ; },
abstract = {Bacterial pathogens adapt rapidly to clinical and within-host selective pressures[1]. Insertion sequences (IS) are transposable elements that can contribute to pathogenic adaptation[2], but their activity and consequences in contemporary clinical populations are not well characterized. Here, combining large-scale genomic surveys with long-read sequencing of clinical isolates and longitudinal gut metagenomes, we quantify pathogen IS dynamics from global patterns to within-host evolution. Across 19,485 publicly available high-contiguity ESKAPEE pathogen genomes, Enterococcus faecium genomes are the most IS dense, dominated by replicative ISL3 family elements, which have proliferated in clinical lineages over the past 30 years. We find extensive chromosomal structural variation, largely involving ISL3, within a new single-hospital collection of bloodstream isolates. Long-read metagenomic sequencing of 28 longitudinal stool samples from 12 haematopoietic cell transplantation (HCT) recipients demonstrates within-host IS dynamics and their regulatory consequences. In one patient, an ISL3 insertion upstream of a folate transporter formed a strong promoter, increasing transcription and improving relative fitness under folate limitation. Enhanced folate scavenging may enable E. faecium to thrive in the setting of microbiome collapse, which is common in HCT and other critically ill patients[3]. Together, these results show that a recent ISL3 expansion is driving rapid evolution in healthcare-associated E. faecium, with consequences for its metabolic fitness that may help explain its increasing clinical burden. Several other pathogens also show elevated IS loads in our survey, which suggests that IS expansion-mediated evolution might be more broadly relevant.},
}

*Enterococcus faecium/genetics/pathogenicity/isolation & purification
*DNA Transposable Elements/genetics
Humans
Genome, Bacterial/genetics
*Adaptation, Physiological/genetics
Metagenome/genetics
Promoter Regions, Genetic/genetics
Feces/microbiology

@article {pmid42186662,
year = {2026},
author = {Mueller, MK and Rousseau, SR and Hark, GM and Shaffer, LR and Rizvanović, BF and Nuelle, JAV},
title = {The Role of the Gut Microbiota in Functional Recovery after Peripheral Nerve Injury: A Narrative Review.},
journal = {Orthopedic reviews},
volume = {18},
number = {},
pages = {162156},
pmid = {42186662},
issn = {2035-8164},
abstract = {INTRODUCTION: While researchers have previously pointed to the peripheral nervous system as a method of transportation for the gut microbiota metabolites to distant organs, researchers have more recently studied the impact of gut microbiota on the peripheral nerves. The purpose of this review was to synthesize the literature on how modulation of the gut microbiota impacts functional recovery following peripheral nerve injury.

METHODS: Electronic searches were conducted in Ovid/Medline and PubMed to identify articles that discuss gut microbiome interventions following peripheral nerve injury in sciatic nerve chronic constriction injury or crush injury animal models and the effects on peripheral nerve regeneration and functional recovery.

RESULTS: Twelve articles met inclusion criteria; all were prospective studies in animal models. Four interventions were identified by the twelve studies, including probiotics, antibiotics, intermittent fasting, and naturopathic compounds. Probiotic treatment and dietary interventions targeted at modulating the gut microbiota improved histological, sensory, and motor outcomes following peripheral nerve injury. While antibiotic treatment negatively impacted recovery after peripheral nerve injury, co-treatment with probiotics or reconstitution of the gut microbiota through fecal microbiota transplantation was able to rescue these negative effects.

CONCLUSION: Alterations in the gut microbiota, whether induced by antibiotics, probiotics, intermittent fasting, or dietary interventions, impact functional recovery, neuropathic pain, and inflammatory processes. However, future research should focus on identifying the specific microbial taxa responsible for neuroregenerative effects and developing standardized protocols for probiotic treatment to optimize improvement in peripheral nerve recovery after injury.},
}

@article {pmid42187072,
year = {2026},
author = {John, JM and Manjarres, Z and Zulkifly, NI and Plumb, AN and Pratt, ML and Sadler, KE},
title = {Male-specific analgesic effects of minocycline in sickle cell disease are mediated by microglia and the microbiome.},
journal = {Pain},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.pain.0000000000004008},
pmid = {42187072},
issn = {1872-6623},
abstract = {Over 50% of individuals with sickle cell disease (SCD) experience chronic pain that is phenotypically distinct from their acute, vaso-occlusive crisis pain. Chronic SCD pain is commonly managed with opioid-based drugs that are associated with unwanted side effects, incomplete pain relief, and-in this population-accessibility issues. Thus, new treatments for chronic SCD pain are desperately needed. Here, we examined the analgesic efficacy of acute minocycline treatment in transgenic SCD mice. Sickle cell disease mice exhibit gut dysbiosis and chronic inflammation. Therefore, we hypothesized that minocycline would provide robust analgesia in this model given the drug's antibiotic and anti-inflammatory properties, respectively. Six days of minocycline treatment reversed chronic mechanical hypersensitivity only in male SCD mice. We identified 2 potential mechanisms underlying these sex-specific effects. First, we observed increased microgliosis only in the dorsal horn of male SCD mice. Minocycline treatment had opposite effects on microglial number in male and female SCD spinal cords. Second, minocycline treatment altered the gut microbiota in a sex-specific fashion; fecal microbiota transplant (FMT) from minocycline-treated female SCD mice induced widespread pain in recipients, whereas FMT from minocycline-treated male SCD mice did not. In summary, these experiments highlight novel sex-specific mechanisms of minocycline analgesia and support future exploration of minocycline use for SCD pain management, but only in male patients.},
}

@article {pmid42188905,
year = {2026},
author = {Yao, Y and Yang, Z and Xie, T and Zhang, Y and Huang, F and Meng, C and Wu, Y},
title = {Multi-Omics Analyses of the Gut Microbiota and Metabolism in Cats with Different Body Conditions and the Effects of Fecal Microbiota Transplantation.},
journal = {Veterinary sciences},
volume = {13},
number = {5},
pages = {},
pmid = {42188905},
issn = {2306-7381},
abstract = {Obesity is increasingly recognized in domestic cats and is associated with metabolic disturbances such as insulin resistance and dyslipidemia. The gut microbiota is considered an important regulator of host metabolism, yet its role in feline obesity remains unclear. In this study, a multi-omics approach was used to investigate gut microbiota composition and metabolic profiles in cats with different body conditions and to evaluate the effects of fecal microbiota transplantation (FMT) on the feline gut microbiota and overall metabolism. In Experiment 1, twenty-four cats were classified as obese, normal, or lean, and their gut microbiota and serum metabolites were analyzed. In Experiment 2, fecal microbiota from obese or lean donors were transplanted into recipient cats. Although overall microbial diversity and community structure did not differ significantly among groups, Coriobacteriaceae and Collinsella were enriched in obese cats, whereas Enterobacteriaceae-related taxa were more abundant in normal-weight cats. Serum metabolomics revealed alterations mainly related to amino acid and antioxidant metabolism, including O-acetylcarnitine, glutathione, and tryptophan metabolism. FMT shifted the recipient gut microbial communities toward their respective donor profiles (obese or lean) but did not significantly affect body weight or routine serum biochemical parameters during the experimental period. These findings suggest that gut microbiota remodeling may influence metabolic processes prior to detectable phenotypic changes in cats.},
}

@article {pmid42192549,
year = {2026},
author = {Zhang, L and Quan, J and Nie, L and He, S and Lin, Y and Liu, X and Zhang, Y and Zhuang, L and Jia, C and Li, M and Wang, Q and Duan, L},
title = {Electroacupuncture prevents CUMS induced depressive-like behaviors by inhibiting microglia-mediated synaptic pruning induced by gut dysbiosis.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {42192549},
issn = {1749-8546},
support = {82305383//National Natural Science Foundation of China/ ; 2023KQNCX017//Ordinary Universities Youth Innovative Talents Project of Guangdong Province Department of Education/ ; 20241088//Project of Guangdong Provincial Administration of Chinese Medicine/ ; 2024A04J4161, 2024A03J0354//Science and Technology Planning Project of Guangzhou/ ; },
abstract = {RATIONALE: Electroacupuncture (EA) has been widely used for depression treatment. Microbiota-gut-brain (MGB) axis plays a vital role in regulating emotional behaviors. However, the potential role of MGB axis in EA-mediated protective effects remains unclear.

METHODS: The protective effects of EA in chronic unpredictable mild stress (CUMS) induced mice were evaluated, and the gut microbiota and metabolic profiles were analyzed. Fecal microbiota transplantation (FMT) was utilized to explore the role of MGB axis in the protective effects of EA. Analyses related to synaptic pruning mediated by microglia were conducted to explore the molecular mechanisms.

RESULTS: In this study, EA treatment prevented depressive-like behaviors in CUMS mice. Mechanistically, EA ameliorated CUMS-induced gut microbiota dysbiosis and inflammation, and partially restored gut microbial metabolism, particularly affecting the abundance of Alistipes and taurine metabolism. Furthermore, EA significantly reduced systemic and hippocampal inflammation. It also attenuated aberrant synaptic pruning in the hippocampus. Moreover, FMT from CUMS mice induced depressive-like behaviors, gut inflammation and microglia-mediated aberrant synaptic pruning, whereas FMT from EA-treated donors exerted protective effects against these impairments.

CONCLUSION: Collectively, our findings suggest that EA prevented CUMS-induced depression-like behaviors and support the involvement of the MGB axis in its protective effects.},
}

@article {pmid42192558,
year = {2026},
author = {Aggad, WS and Ghosh, R and Almohaimeed, HM and Mohammedsaleh, ZM and Saleh, FM and Almars, AI and Jyothi, SR and Panigrahi, R and Kumer, A and Dhara, B},
title = {Exosome-mediated gut-brain axis signaling in neurodegenerative diseases: Mechanisms, experimental evidence, and therapeutic perspectives-A narrative review.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.70226},
pmid = {42192558},
issn = {2576-2095},
support = {PNURSP2026R213//Princess Nourah Bint Abdulrahman University/ ; },
abstract = {The stomach and the brain are connected by a sophisticated two-way communication mechanism called the gut-brain axis. Extracellular vesicles, particularly exosomes, that move bioactive substances between the stomach and the brain, such as proteins, lipids, metabolites, and microRNAs, may improve the gut-brain axis. In the past years, the role of exosome-mediated communication has been recognized as significant in relation to the etiology, continued progression, and potential treatment of neurodegenerative disorders. The authors of this review article present a summary of the current understanding of the relationship of gut microbiome, exosome biogenesis, and the pathophysiological development of neurodegenerative diseases. Evidence from laboratory studies, animal studies, and newly emerging human studies suggests that microbiome-based metabolites and inflammatory mediators may modulate how exosomes are produced, what they carry, and how they interact with the blood-brain barrier. These exosomal signals may impact neuroinflammation, neuronal signaling, and the spread of pathological proteins of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In addition, they examine some possible ways to target the gut-brain axis from a therapeutic perspective, including manipulating the gut microbiome, providing probiotics and/or prebiotics, performing fecal microbiota transplantation, and/or using engineered extracellular vesicles as vehicles for drug delivery. The authors also outline some of the methodological differences that make it difficult to assess the effects of exosomes.},
}

@article {pmid42193296,
year = {2026},
author = {Pinton, P},
title = {Microbiome-Based Therapies in Ulcerative Colitis: Mechanisms, Clinical Evidence, and a Precision-Medicine Framework.},
journal = {Biomedicines},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/biomedicines14050969},
pmid = {42193296},
issn = {2227-9059},
abstract = {Microbiome-based therapies are reshaping the therapeutic landscape for ulcerative colitis (UC), offering new avenues for disease management beyond conventional immunomodulatory and biologic treatments. UC remains a chronic, relapsing condition with significant unmet clinical needs, as many patients fail to achieve sustained remission or experience adverse effects with current therapies. The gut microbiome has emerged as a central contributor to UC pathogenesis, influencing epithelial barrier integrity, immune homeostasis, and metabolic signaling. Interventions such as fecal microbiota transplantation (FMT) and defined microbial consortia have demonstrated proof-of-concept efficacy in early-phase clinical trials, each leveraging distinct mechanistic strategies. FMT, as a broad ecological intervention, restores microbial diversity and functional redundancy, potentially addressing multiple pathogenic mechanisms simultaneously. In contrast, defined consortia enable precise targeting of specific metabolic and immunological pathways, including short-chain fatty acid production, bile-acid remodeling, epithelial barrier reinforcement, immune modulation, and succinate degradation. Recent clinical evidence suggests that consortia with broader mechanistic coverage may achieve more consistent biological activity than narrowly focused designs. This review synthesizes mechanistic and clinical insights across broad and defined microbial consortia, integrates evidence from randomized controlled trials and early-phase LBP studies, and outlines a precision-medicine framework to guide therapy selection. We highlight the importance of aligning therapeutic mechanisms with patient-specific microbial, metabolic, and immune profiles, and discuss future directions including biomarker-guided stratification, hybrid consortia, and adaptive trial designs. Advancing both broad and defined approaches, while incorporating ecological principles, mechanistic understanding, and patient stratification, will be essential to realizing the full therapeutic potential of microbiome-based therapies in UC.},
}

@article {pmid42193302,
year = {2026},
author = {Marchitto, SA and Abbatecola, G and Zeidan, RS and Morgan, L and Calvani, R and Picca, A and Schlögl, M and Tosato, M and Leeuwenburgh, C and Anton, SD and Landi, F and Marzetti, E and Cacciatore, S},
title = {The Gut-Muscle Axis in Sarcopenia: Mechanisms, Evidence Gaps and Translational Challenges.},
journal = {Biomedicines},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/biomedicines14050976},
pmid = {42193302},
issn = {2227-9059},
support = {D1.2024//Università Cattolica del Sacro Cuore/ ; D1.2025//Università Cattolica del Sacro Cuore/ ; N/A//Centro Studi Achille e Linda Lorenzon/ ; P30 AG028740/AG/NIA NIH HHS/United States ; 2022YNENP3//Ministero dell'università e della ricerca/ ; },
abstract = {Sarcopenia is an age-related skeletal muscle disorder characterized by reduced muscle mass, strength, and physical performance, as well as increased risk of disability, hospitalization, and mortality. Emerging evidence suggests that gut microbiota alterations may contribute to muscle decline via a microbiota-gut-muscle axis, acting as a context-dependent modulator rather than a primary causal driver. This narrative review synthesizes mechanistic, clinical, and translational evidence linking gut dysbiosis to sarcopenia. Preclinical studies show that microbiota modulation (e.g., antibiotics, probiotics, prebiotics, postbiotics, fecal microbiota transplantation) affects muscle mass, strength, and metabolism through pathways including inflammation, mitochondrial dysfunction, altered short-chain fatty acid production, and impaired anabolic signaling. In humans, observational studies associate lower microbial diversity and reduced short-chain fatty acid-producing taxa with poorer muscle outcomes, but findings are heterogeneous and non-causal. Interventional trials remain limited and characterized by small sample sizes, with effects more consistent for functional outcomes than muscle mass. Overall, the gut microbiota represents a modifiable contributor within the complex biology of sarcopenia. Future studies should integrate microbiome profiling and multi-omics approaches within well-designed clinical trials to identify responder phenotypes and define the role of microbiota-targeted strategies within multimodal interventions.},
}

@article {pmid42194001,
year = {2026},
author = {Zhao, Z and Wang, J and Wu, Z and Ye, L and Wang, J and Wang, Y and Zhao, Y and Zhang, H and Luo, C and Tong, J},
title = {Integrated Multi-Omics Analysis Explores the Protective Effects and Potential Mechanisms of Pulsatilla chinensis on Canine Antibiotic-Associated Diarrhea.},
journal = {Biomolecules},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/biom16050650},
pmid = {42194001},
issn = {2218-273X},
support = {32272904//National Natural Science Foundation of China/ ; 32373086//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Dogs ; *Diarrhea/chemically induced/drug therapy/veterinary/prevention & control/metabolism ; Multiomics ; *Anti-Bacterial Agents/adverse effects ; *Pulsatilla/chemistry ; Metabolomics ; *Plant Extracts/pharmacology/chemistry ; Cytokines ; },
abstract = {Diarrhea is a common gastrointestinal disorder in animals, often worsened by antibiotic use. Pulsatilla chinensis (PC) is traditionally used for gastrointestinal issues, but its bioactive constituents and mechanisms remain unclear. This study investigated the preventive effects of PC in a canine model of antibiotic-associated diarrhea using an integrated multi-omics approach. LC-MS identified key constituents of PC, including anemoside B4, berberine, stigmasterol, and quercetin. In silico analyses predicted that stigmasterol and quercetin target EGFR and AKT1, modulating inflammation and epithelial repair via PI3K-Akt and IL-17 signaling pathways. In vivo, treatment with PC significantly reduced serum pro-inflammatory cytokines such as TNF-α and IL-6 and elevated immune markers including IgG and IgA compared to the control group. Furthermore, 16S rRNA analysis revealed that PC restored gut microbial diversity, reflected by increased Sobs and Chao1 indices, enriched beneficial Lactobacillus, and decreased the abundance of inflammation-associated taxa such as Proteobacteria, Desulfobacterota, and Escherichia-Shigella. These findings suggest that PC suppresses inflammation and remodels the gut microbiome, providing a mechanistic basis for its use as an herbal alternative to antibiotics. Future studies should include fecal microbiota transplantation and targeted metabolomics to establish causality and optimize therapeutic strategies.},
}

Animals
Dogs
*Diarrhea/chemically induced/drug therapy/veterinary/prevention & control/metabolism
Multiomics
*Anti-Bacterial Agents/adverse effects
*Pulsatilla/chemistry
Metabolomics
*Plant Extracts/pharmacology/chemistry
Cytokines

@article {pmid42194897,
year = {2026},
author = {Lau, WL and Li, W and Sumida, K and Kalantar-Zadeh, K},
title = {The Role of Diet and Gut Microbiome in CKD Progression and Therapy.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103934},
pmid = {42194897},
issn = {2077-0383},
abstract = {There is a bidirectional relationship between chronic kidney disease (CKD) and an altered gut microbiome, with gut-derived uremic toxins contributing to cardiovascular-kidney-metabolic effects. In this review, we summarize the interplay between diet, the intestinal microbiota and systemic sequelae including CKD progression, cardiovascular morbidity and cognitive decline. We discuss the current state of knowledge regarding microbiota-modulating therapies that have the potential to delay CKD complications such as plant-dominant diets, oral adsorbents, prebiotics/probiotics, fecal microbiota transplantation and exercise.},
}

@article {pmid42197000,
year = {2026},
author = {Shehata, F and Dwyer, KM and McGee, SL and Rivera, LR},
title = {Gut Microbiome Dysbiosis in Metabolic Syndrome: Current Evidence and Emerging Perspectives.},
journal = {Nutrients},
volume = {18},
number = {10},
pages = {},
doi = {10.3390/nu18101540},
pmid = {42197000},
issn = {2072-6643},
mesh = {Humans ; *Metabolic Syndrome/microbiology/therapy ; *Dysbiosis/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Probiotics/administration & dosage ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; Synbiotics/administration & dosage ; },
abstract = {The gut microbiota plays a crucial role in human metabolism, and disruptions to its composition, particularly reductions in bacterial diversity, have been increasingly associated with the development of metabolic syndrome (MetS). MetS encompasses a constellation of interrelated metabolic risk factors, including central obesity, insulin resistance, dyslipidemia, and hypertension, which collectively elevate the risk of cardiovascular and cerebrovascular disease. A comprehensive understanding of the mechanisms underlying MetS is therefore critical for the development of effective preventive and therapeutic strategies. Complex interactions between the gut microbiota and host metabolic pathways are mediated by multiple factors, including microbial metabolites, inflammatory signaling, and host immune responses. This narrative review characterizes the clinical manifestations of MetS and alterations in gut microbiota composition, characterized by an overrepresentation of potentially pathogenic taxa and a concomitant decline in beneficial microbial species. In addition, we discuss current and emerging approaches to microbiota modulation, including prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, and evaluate their potential roles in the prevention and management of MetS. We identify critical evidence gaps and propose research priorities for evidence-based clinical strategies for MetS management and prevention.},
}

Humans
*Metabolic Syndrome/microbiology/therapy
*Dysbiosis/microbiology/complications
*Gastrointestinal Microbiome/physiology
Probiotics/administration & dosage
Prebiotics/administration & dosage
Fecal Microbiota Transplantation
Synbiotics/administration & dosage

@article {pmid42197001,
year = {2026},
author = {Lupu, VV and Nedelcu, AH and Miron, I and Anton, SC and Sasaran, MO and Frasinariu, OE and Jechel, E and Bozomitu, LI and Chisnoiu, T and Anton, CR and Marginean, CO and Morariu, ID and Mihai, CM and Anton, E and Lupu, A},
title = {Early Gut Microbiota and Neurodevelopmental Trajectories: Implications for Pediatric Neuropsychiatric Vulnerability-A Narrative Review.},
journal = {Nutrients},
volume = {18},
number = {10},
pages = {},
doi = {10.3390/nu18101541},
pmid = {42197001},
issn = {2072-6643},
mesh = {Humans ; Neurodevelopment ; *Gastrointestinal Microbiome/physiology ; *Neurodevelopmental Disorders/microbiology ; Dysbiosis/microbiology ; Child ; Brain/growth & development ; Probiotics ; Prebiotics/administration & dosage ; Neuronal Plasticity ; },
abstract = {Neurodevelopment is a dynamic and multifactorial process, critical in the early stages of life, involving the formation of neural networks, the establishment of synapses, and the maturation of cognitive, social and emotional circuits. In this context, the gut microbiome emerges as an essential regulator of neurodevelopment, exerting influences through multiple biochemical and immunological mechanisms that define the "gut-brain axis". The microbiota modulates neurodevelopment by regulating neurotransmitters (serotonin, dopamine, GABA), the production of microbial metabolites, including short-chain fatty acids, the modulation of inflammatory cytokines, and vagal signaling to the central nervous system. Recent evidence highlights the role of microbiota in modulating microglia, synaptogenesis, dendritic maturation, and neuronal plasticity, emphasizing how these processes are influenced by microbial activity rather than providing a comprehensive treatise on plasticity itself. Gut microbiota disturbances, or dysbiosis, have been associated with various neuropsychiatric and neurodevelopmental disorders, contributing to cognitive, behavioral, and emotional dysfunctions. This article summarizes, in a narrative manner, the main dysbiosis patterns identified in these disorders and the biological mechanisms by which the microbiome influences neuronal development and function, including immune-neuronal interactions, metabolomic modulation, and neuroendocrine signaling. Finally, emerging directions of intervention aimed at adjusting the microbial profile, such as dietary adjustment, the use of probiotics, prebiotics, symbiotics, and fecal microbiota transplantation, are presented with the aim of positively influencing neurodevelopment and preventing or ameliorating associated dysfunctions. This review emphasizes the need for longitudinal, rigorous, and controlled clinical trials to validate the efficacy of microbiota modulation strategies and to substantiate their integration into individualized pediatric management protocols.},
}

Humans
Neurodevelopment
*Gastrointestinal Microbiome/physiology
*Neurodevelopmental Disorders/microbiology
Dysbiosis/microbiology
Child
Brain/growth & development
Probiotics
Prebiotics/administration & dosage
Neuronal Plasticity

@article {pmid42197004,
year = {2026},
author = {Wang, M and Lyu, Y and Zhang, J and Wang, Y and Yang, Y and Mao, YH},
title = {FMT from Exercise and Konjac Glucomannan Preconditioned Donors Rescues Antibiotic-Induced Dysbiosis with Enhanced Ecological Restoration in Mice.},
journal = {Nutrients},
volume = {18},
number = {10},
pages = {},
doi = {10.3390/nu18101544},
pmid = {42197004},
issn = {2072-6643},
support = {2023ZDZX2035; 2024ZDZX2061//Guangdong Scientific Research Platform and Projects for the Higher-educational Institution (Key Area Project)/ ; SL2024A04J01093//the Guangzhou Fundamental and Applied Research/ ; No.82030098//National Natural Science Foundation of China/ ; S202410585045 and 202410585015//the College Students Innovation and Entrepreneurship Training Program/ ; 2023A1515010004//the Guangdong Basic and Applied Basic Research Foundation/ ; },
mesh = {Animals ; *Dysbiosis/therapy/chemically induced/microbiology ; *Fecal Microbiota Transplantation/methods ; *Mannans/pharmacology ; *Anti-Bacterial Agents/adverse effects ; Mice ; *Gastrointestinal Microbiome/drug effects ; Male ; *Physical Conditioning, Animal ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Although antibiotics have a wide range of applications in medical clinical practice and possess significant clinical value, their inevitable contribution to gut microbiome dysbiosis warrants attention. Our previous research has confirmed that the combined intervention of exercise and konjac glucomannan (KGM) has a better regulatory effect on gut dysbiosis in mice compared with individual interventions.

METHODS: This study aims to further investigate whether this effect can be transmitted through fecal microbiota transplantation (FMT), and to compare the recovery effects of autologous FMT (a-FMT), fecal microbiota transplantation after exercise combined with KGM intervention (EK-FMT), and combinative intervention with exercise and KGM (EXE-KGM) on gut microbiome dysbiosis. Sample sizes ranged from five to six animals.

RESULTS: The results showed that the a-FMT group recovered α diversity the fastest, including Chao, Shannon, and Simpson indices(p < 0.05), within 2 weeks after transplantation when compared with the CTL group. At the end of the experiment, the Bray-Curtis distance of the a-FMT group was closest to the CTL group, while the EXE-KGM group had delayed recovery, there was no significant difference between the EK-FMT group and the EXE-KGM group. Metagenomic analysis and metabolomics analysis indicated that the arginine synthesis and metabolism pathways (KEGG: map00471, map00473, arginine biosynthesis) played a core role in the restoration of the microbiota.

CONCLUSIONS: The results of this experiment indicate that EK-FMT group can partially transfer the regulatory effects of combined exercise and KGM intervention, a-FMT accelerates the recovery speed of the gut microbiome and arginine metabolism may play an important role in it. This finding provides a theoretical basis and practical direction for special populations to receive special donor fecal treatment.},
}

Animals
*Dysbiosis/therapy/chemically induced/microbiology
*Fecal Microbiota Transplantation/methods
*Mannans/pharmacology
*Anti-Bacterial Agents/adverse effects
Mice
*Gastrointestinal Microbiome/drug effects
Male
*Physical Conditioning, Animal
Mice, Inbred C57BL

@article {pmid42197026,
year = {2026},
author = {Alsinani, Y and Rostamkhani, F and Shirvani, H},
title = {Exercise and the Gut Microbiome: From Mechanisms to Clinical Applications.},
journal = {Nutrients},
volume = {18},
number = {10},
pages = {},
doi = {10.3390/nu18101565},
pmid = {42197026},
issn = {2072-6643},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Exercise/physiology ; Fatty Acids, Volatile/metabolism ; },
abstract = {Background/Objectives: The gut microbiome is a critical regulator of host metabolism, immunity, and the gut-brain axis. Exercise is a promising non-pharmacological modulator of microbial ecology, yet human evidence remains heterogeneous and the translational gap persists. This narrative review synthesizes mechanisms, human and animal evidence, and future directions for the exercise-gut microbiome axis. Methods: PubMed, Scopus, Web of Science, and SID were searched for articles published between January 2000 and February 2025. Keywords included exercise, physical activity, gut microbiome, gut microbiota, short-chain fatty acids, and gut-muscle axis. From 218 initial records, 89 original studies (47 human, 42 animal) met inclusion criteria and were critically appraised. Results: Exercise modulates the gut microbiome via splanchnic hypoperfusion, hyperthermia, altered transit time, and immune-mediated barrier regulation. Moderate-intensity continuous training consistently increases alpha diversity and enriches butyrate-producing taxa (Faecalibacterium prausnitzii, Roseburia hominis) and mucin-degrading Akkermansia muciniphila. High-intensity interval training transiently increases intestinal permeability in untrained individuals but, following adaptation, stimulates butyrate production via lactate cross-feeding metabolism-a recent breakthrough. Effects are transient and reversible upon detraining. Animal models establish causality through fecal microbiota transplantation; human randomized controlled trials demonstrate modest, intensity-dependent, and highly individualistic responses. Emerging evidence supports the gut-muscle axis in sarcopenia and personalized exercise prescription guided by microbiome profiling. Conclusion: Exercise shows promise as a low-cost modulator of the gut microbiome for enriching health-associated taxa and improving metabolic outcomes. Definitive evidence linking exercise-induced microbial shifts to enhanced athletic performance in humans remains lacking. Future research requires diet-controlled randomized controlled trials with ≥12-week interventions, shotgun metagenomics, and mechanistic validation of the gut-muscle axis in humans.},
}

Humans
*Gastrointestinal Microbiome/physiology
Animals
*Exercise/physiology
Fatty Acids, Volatile/metabolism

@article {pmid42197071,
year = {2026},
author = {Jing, Y and Bai, X and Ji, Y and Zhai, Z and Zhao, Y and Hao, Y},
title = {Fecal Microbiota Transplantation from Toddler Donors Ameliorated DSS-Induced Colitis in Mice by Reshaping Gut Microbiota.},
journal = {Nutrients},
volume = {18},
number = {10},
pages = {},
doi = {10.3390/nu18101611},
pmid = {42197071},
issn = {2072-6643},
support = {No. 2022YFF1100105//the National Key R&D Program of China/ ; },
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Colitis/therapy/chemically induced/microbiology ; *Gastrointestinal Microbiome ; Dextran Sulfate ; Mice ; Male ; Disease Models, Animal ; Humans ; Colon/pathology/microbiology ; Mice, Inbred C57BL ; Dysbiosis/therapy ; Feces/microbiology ; Intestinal Barrier Function ; Cytokines/metabolism ; },
abstract = {Background/Objectives: Gut microbiota dysbiosis is a key driver of inflammatory bowel disease (IBD), and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy. In this study, we investigated the protective effects of toddler-derived FMT against colitis and elucidated the underlying mechanisms. Methods: Firstly, fecal microbiota from healthy toddlers was transplanted into antibiotic-pretreated mice, establishing stable colonization between days 14 and 21 post-transplantation. Results: In a dextran sulfate sodium-induced colitis model, FMT significantly ameliorated colitis symptoms, including reduced disease activity index and restored colon length. Toddler-derived FMT improved the intestinal barrier by preserving goblet cell density and enhancing MUC2 expression. Meanwhile, colonic inflammation was alleviated by FMT, which suppressed pro-inflammatory cytokines, reduced CD4[+] T cell counts, and associated with downregulation of JAK/STAT-related transcripts. 16S rRNA sequencing revealed that FMT remodeled the gut microbiota by enriching beneficial genera, including Bacteroides, Parabacteroides, Blautia, and Akkermansia, which correlated positively with colon length and negatively with inflammatory markers. Conclusions: These findings provided a theoretical foundation that toddler-derived microbiota represents a potential donor source for FMT in IBD.},
}

Animals
*Fecal Microbiota Transplantation/methods
*Colitis/therapy/chemically induced/microbiology
*Gastrointestinal Microbiome
Dextran Sulfate
Mice
Male
Disease Models, Animal
Humans
Colon/pathology/microbiology
Mice, Inbred C57BL
Dysbiosis/therapy
Feces/microbiology
Intestinal Barrier Function
Cytokines/metabolism

@article {pmid42197467,
year = {2026},
author = {Bartocci, B and Del Gaudio, A and Murgiano, M and Papa, A and Cammarota, G and Gasbarrini, A and Scaldaferri, F and Lopetuso, LR},
title = {Emerging Role of Gut Microbiota in Modulating Response to Therapies in IBD.},
journal = {Microorganisms},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/microorganisms14051082},
pmid = {42197467},
issn = {2076-2607},
abstract = {The gut microbiota is increasingly recognized as a key contributor in the pathogenesis and progression of inflammatory bowel disease (IBD). Compared with healthy individuals, patients with IBD show marked dysbiosis, characterized by reduced microbial diversity, an expansion of facultative anaerobes such as Proteobacteria, and a depletion of obligate anaerobes within the Firmicutes phylum. These changes have been implicated in the perpetuation of intestinal inflammation, disruption of mucosal immune homeostasis, and altered metabolic functions, further underscoring the microbiota's relevance in IBD pathophysiology. However, microbiota-driven insights have not yet been consistently translated into therapeutic stratification or clinical decision-making. A major challenge lies in the complex and dynamic interplay between the gut microbiota and various treatment modalities, including conventional immunosuppressants, biologics, and small-molecule inhibitors. While accumulating evidence suggests that IBD treatments may modulate microbial composition and function, it remains unclear whether these changes represent a direct pharmacological effect or are secondary to inflammation control. Additionally, there is a lack of comparative data on microbiota profiles associated with differential responses to various therapeutic classes, limiting the implementation of microbiota-informed precision medicine. In this review, we synthesize current evidence on the association between gut microbiota composition and treatment outcomes, focusing on biologic agents and small-molecule therapies. Furthermore, we discuss the potential of microbiota-targeted strategies, such as fecal microbiota transplantation (FMT) and precision probiotics, in enhancing therapeutic response. A deeper understanding of host-microbe interactions could enable a more personalized and effective approach to IBD management.},
}

@article {pmid42198436,
year = {2026},
author = {Zou, Y and Hu, RT and Yu, Q and Rao, PL and Cui, HY and Wei, WJ and Cai, X and Li, HK and Shen, YH},
title = {Liuweidihuang Pill Attenuates Early Bleomycin-Induced Pulmonary Fibrosis in Mice and Is Associated with Gut Microbiome.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {5},
pages = {},
doi = {10.3390/ph19050762},
pmid = {42198436},
issn = {1424-8247},
support = {ZD2021CY001//Shanghai Municipal Science and Technology Major Project/ ; },
abstract = {Background: Pulmonary fibrosis (PF) is a chronic, progressive lung disease with limited treatment options. Liuweidihuang pill (LDP), a classical formula for kidney-yin deficiency, has been reported to have anti-inflammatory and anti-oxidative activities, suggesting potential relevance to PF. Purpose: This study evaluated whether LDP attenuates bleomycin-induced PF in mice and whether gut microbiota remodeling may contribute to its protective effects. Methods: Mice received intratracheal bleomycin followed by LDP gavage. Lung pathology was assessed by hematoxylin-eosin (HE) and Masson staining. Inflammatory cytokines, hydroxyproline (HYP), and α-SMA were measured. LDP and LDP-containing serum were profiled by UPLC-MS. The gut microbiota was analyzed using 16S rDNA sequencing. To further explore whether microbiota-related changes were associated with the protective phenotype, fecal microbiota transplantation (FMT) and probiotic VSL#3 intervention were performed. In addition, LDP-containing serum was tested in a TGF-β1-induced EMT model in A549 cells. Results: LDP reduced lung index, inflammatory infiltration, interstitial fibrosis, α-SMA expression, HYP content, and pro-inflammatory cytokine levels in bleomycin-treated mice. These effects were accompanied by gut microbiota remodeling and transcriptomic changes related to inflammation, metabolism, and fibrosis. VSL#3 partially reproduced the protective phenotype, whereas FMT showed limited efficacy. LDP-containing serum had a limited inhibitory effect on EMT inhibited EMT in vitro, suggesting that systemic host responses may contribute to the in vivo effect. Conclusions: LDP attenuated early bleomycin-induced PF and was associated with reduced inflammation and gut microbiota remodeling. These findings suggest a possible role for microbiota-host interactions in LDP-associated protection; however, causal directionality, key active effectors, and protein-level pathway validation remain unresolved.},
}

@article {pmid42198457,
year = {2026},
author = {Pastras, P and Aggeletopoulou, I and Psalti, V and Triantos, C},
title = {Gut Microbiota in Irritable Bowel Syndrome and Inflammatory Bowel Disease: Differences in Pathophysiology, Biomarkers, and Treatment Implications.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {5},
pages = {},
doi = {10.3390/ph19050783},
pmid = {42198457},
issn = {1424-8247},
abstract = {Alterations in the intestinal microbiota have been implicated in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). However, their biological significance and therapeutic implications differ substantially between the two conditions. Although dysbiosis is a common feature, the mechanisms by which alterations in the microbiota contribute to disease pathophysiology and clinical expression are distinct. Some pathways are more prominent in IBS (e.g., the gut-brain axis), whereas others are more prominent in IBD (e.g., reduced microbial diversity). Equally important are pathways that appear to play a role exclusively in IBD [e.g., Adherent-invasive Escherichia coli (AIEC) and Paneth cells], as well as others that seem to be specific to IBS (e.g., mast cell activation). In IBD, microbiota changes are primarily linked to immune dysregulation, mucosal barrier impairment, and inflammation-driven pathways, whereas in IBS, they are mainly associated with functional disturbances mediated by neuroimmune signaling and microbial metabolites. Furthermore, several microbiome-associated biomarkers differ between these two diseases, and some are already assessed by international guidelines. Although the microbiota plays a key role in IBS and IBD pathophysiology, microbiome-based treatments remain limited, especially in IBD. There are clinically available treatments in IBS (e.g., rifaximin, low-FODMAP diet), but in IBD, only the probiotic VSL#3 is guideline-approved in ulcerative colitis pouchitis prophylaxis. Nevertheless, the dynamic nature of the microbiota continues to support the investigation of already studied (e.g., probiotics, fecal microbiota transplantation) and potential novel therapeutic approaches at the research level. The aim of this review is to compare the gut-microbiota-related pathophysiological pathways and biomarkers between IBS and IBD, to summarize the microbiome-related medications that have already been studied in both diseases, and to suggest new potential therapeutic options based on the gut microbiota.},
}

@article {pmid42198975,
year = {2026},
author = {Zhang, J and Bai, J and Ren, X and Ye, X and Tan, M and Yang, Y and Li, L and Fu, Z},
title = {[Fecal microbiota transplantation inhibits colonic tumor growth in mice by suppressing the TLR4/MyD88/NF-κB signaling pathway].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {46},
number = {5},
pages = {1139-1148},
doi = {10.12122/j.issn.1673-4254.2026.05.18},
pmid = {42198975},
issn = {1673-4254},
mesh = {Animals ; Myeloid Differentiation Factor 88/metabolism ; *Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Mice ; Signal Transduction ; *Colonic Neoplasms/therapy ; *Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Transforming Growth Factor beta1/metabolism ; Cell Line, Tumor ; Killer Cells, Natural ; Male ; },
abstract = {OBJECTIVES: To explore the effects of fecal microbiota transplantation (FMT) on immune function and tumor inhibition in mice.

METHODS: C57BL/6N mice were divided into blank control group, tumor bearing model group, and FMT intervention group (n=6). In the latter two groups, the mice bearing subcutaneous MC38 colon cancer cell xenografts were treated with daily gavage of normal saline or 0.1 mL of bacterial suspension. The changes in tumor mass and volume were recorded, and peripheral blood natural killer (NK) cell counts and NKG2A and NKG2D receptor expressions were analyzed using flow cytometry; serum lipopolysaccharide (LPS) levels were measured with ELISA. The binding ability of NF‑κB to the TGF‑β1 gene promoter was analyzed with JASPAR. The mRNA and protein expressions of TLR4, MyD88, NF‑κB, TGF‑β1, perforin and granzyme in the tumor tissues were detected using RT qPCR and Western blotting, and the changes in gut microbiota were analyzed using 16S high throughput sequencing.

RESULTS: FMT significantly reduced tumor mass and volume in the tumor-bearing mice. Peripheral CD3⁻NK1.1⁺ cell counts were significantly decreased in the tumor-bearing mice regardless of FMT treatment, which, however, reversed the increase of CD3[-]NKG2A[+] cells and reduction of CD3[-]NKG2D[+] cells and reduced serum LPS levels in the mouse models. Molecular docking and JASPAR analysis confirmed LPS-TLR4 binding (binding energy: -13.1 kcal/mol) and identified NF-κB binding sites on TGF‑β1 promoter. FMT downregulated mRNA and protein expressions of TLR4, MyD88, NF‑κB and TGF‑β1 and upregulated perforin and granzyme mRNA expressions in the xenografts. FMT also restored gut microbiota diversity and composition, and reversed the increase of Proteobacteria and decrease of Lactobacillus murinus in the tumor-bearing mice.

CONCLUSIONS: FMT modulates the relative abundances of intestinal Proteobacteria and Lactobacillus murinus in tumor-bearing mice, and inhibits tumor growth by suppressing the TLR4/MyD88/NF‑κB signaling axis, down-regulating TGF-β1 expression, and promoting NK cell activation.},
}

Animals
Myeloid Differentiation Factor 88/metabolism
*Toll-Like Receptor 4/metabolism
NF-kappa B/metabolism
Mice
Signal Transduction
*Colonic Neoplasms/therapy
*Fecal Microbiota Transplantation
Mice, Inbred C57BL
Transforming Growth Factor beta1/metabolism
Cell Line, Tumor
Killer Cells, Natural
Male

@article {pmid42199152,
year = {2026},
author = {Zhang, W and Song, Y and Li, C and Luo, Y and Shao, M and Guo, F and Wei, F and Fan, X and Guo, W and Xu, F and Sang, Y and Zhang, D and Zhou, Y and Wang, L and Kang, Z and Yang, Y and Song, C and Liu, Y and Ma, X and Wang, J and Li, C and Ma, S and Zhao, L and Qin, Z and Xing, G and Zhao, Q and Li, J and Song, S and Zhao, D and Huang, T and Wang, Q and Zhao, Y and Qin, G},
title = {Canagliflozin Alleviates Diabetic Glomerular Endothelial Injury via Melibiose in a Microbiota-Dependent Manner.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e17222},
doi = {10.1002/advs.202517222},
pmid = {42199152},
issn = {2198-3844},
support = {82170839//National Natural Science Foundation of China/ ; U23A20414//National Natural Science Foundation of China/ ; 82470876//National Natural Science Foundation of China/ ; 82300930//National Natural Science Foundation of China/ ; 251111311500//Key Research and Development Program of Henan Province/ ; 242300421272//Natural Science Foundation of Henan Province/ ; LHGJ20230200//Henan Joint Construction Program/ ; SBGJ202301006//Science and Technology Research Project of Henan Province/ ; },
abstract = {Canagliflozin reduces albuminuria in patients with diabetic kidney disease (DKD) beyond its glucose-lowering effect, but the mechanisms remain unclear. We analyzed 85 patients treated with canagliflozin and 85 controls over 26 weeks to explore whether the gut microbiome and its metabolites contribute to renoprotection. Canagliflozin remodeled the gut microbiota, notably enriching Roseburia intestinalis and increasing plasma melibiose levels. In mice, canagliflozin alleviated glomerular endothelial injury and albuminuria. Similar effects were replicated by fecal microbiota transplantation, Roseburia intestinalis, or melibiose administration. Mechanistically, melibiose bound to and activated glyoxalase 1, reduced methylglyoxal, and suppressed the AGE-RAGE pathway, preserving glomerular endothelial integrity. Furthermore, oral melibiose precursor supplementation reduced albuminuria in patients with early-stage DKD. These findings suggest the involvement of a gut-kidney axis in the renoprotective effects of canagliflozin and indicate that melibiose may serve as a potential therapeutic strategy for DKD.},
}

@article {pmid41981603,
year = {2026},
author = {Liu, Y and Chen, C and Liu, H and Wang, W and Zhou, X and Guo, M and Zhao, J and Zeng, Z and Xu, L},
title = {Decoding the gut microbiota-immune dialogue: from bidirectional axis to therapeutic applications.},
journal = {Journal of nanobiotechnology},
volume = {24},
number = {1},
pages = {},
pmid = {41981603},
issn = {1477-3155},
support = {82160503, 82272812//National Natural Science Foundation of China/ ; QKHZC-2020-4Y156, QKH-JC-2018-1428, QKHJC-ZK-2022-624//Project of the Guizhou Provincial Department of Science and Technology/ ; },
abstract = {UNLABELLED: The gut microbiota (GM), a highly complex micro-ecosystem residing within the host’s gastrointestinal tract, works in conjunction with the gut immune system to form a precise bidirectional regulatory network, that maintains symbiotic homeostasis and overall host health. Cumulative evidence has demonstrated that the critical impact of the bidirectional causal relationship between the GM and the gut immune system on host development and the dynamic progression of disease. However, many challenges remain in this research field, including the mechanism complexity, therapeutic effect differences due to individual heterogeneity, long-term safety, and clinical transformation bottlenecks) that need to be urgently broken through. Therefore, the in-depth analysis of these issues is of great theoretical and practical significance for clarifying the intrinsic connection between the GM and gut immunity, particularly in elucidating the pathogenesis of related clinical diseases such as inflammatory bowel disease (IBD), tumors, and autoimmune diseases (AD). We systematically outline the interaction mechanisms between the microbiota and the immune system, including compositional structure (microbiota diversity and immune system composition), development and maturation processes (early microbiota colonization and immune system establishment), and functional regulation (immune cell differentiation and maintenance of mucosal barrier integrity), as well as their associations with clinical diseases. Finally, we discuss some key considerations for the developing of innovative treatment strategies, such as microbial-targeted interventions, fecal microbiota transplantation (FMT), and synergistic use of immunomodulatory drugs, with the aim of providing a new paradigm for the precise intervention of related diseases.

GRAPHICAL ABSTRACT: [Image: see text]},
}

@article {pmid42183271,
year = {2026},
author = {Zhang, H and Zhang, K and Liu, J and Luo, H},
title = {Multidimensional exploration of the relationship between gut microbiota and colorectal cancer: focus on clinical tumorigenesis and treatment.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1807247},
pmid = {42183271},
issn = {1664-3224},
mesh = {Humans ; *Colorectal Neoplasms/therapy/microbiology/etiology/immunology/metabolism/pathology ; *Gastrointestinal Microbiome/immunology ; Animals ; Dysbiosis ; *Carcinogenesis ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; },
abstract = {The gut microbiota has received considerable attention in the field of colorectal cancer (CRC) research in recent years. In this review, we have explored the multifaceted relationship between the gut microbiota and CRC progression and treatment. The composition, distribution, and normal physiological functions of the gut microbiota have been summarized, along with the association between gut dysbiosis and CRC based on the body of evidence from animal experiments and clinical studies. In addition, we have discussed the mechanisms through which specific microbial configurations or microbiota-derived metabolites may contribute to colorectal carcinogenesis, including genotoxic effects, inflammation, and immune dysregulation. The impact of the gut microbiota on the efficacy of chemotherapy, radiotherapy, and immunotherapy, and new treatment strategies based on the gut microbiota, such as probiotic intervention, prebiotic application, and fecal microbiota transplantation have also been explored. Despite some promising outcomes, the specific carcinogenic microorganisms have not been identified, and it is challenging to distinguish association from causation, determine the influence of individual differences, and translate the research to clinical applications. In the future, more rigorous longitudinal studies, gnotobiotic models with defined microbial communities, and mechanistic interventional studies are needed to strengthen causal inference, and provide practical guidance for CRC prevention and treatment. Beyond summarizing reported associations, this review proposes a microbiota-immune-metabolism-therapy axis by integrating tumorigenic mechanisms, immune contexture, and treatment responsiveness into a single translational framework.},
}

Humans
*Colorectal Neoplasms/therapy/microbiology/etiology/immunology/metabolism/pathology
*Gastrointestinal Microbiome/immunology
Animals
Dysbiosis
*Carcinogenesis
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Prebiotics

@article {pmid42184295,
year = {2026},
author = {Wong, SH},
title = {The human microbiome at translational crossroads: an ecological and causal perspective.},
journal = {Singapore medical journal},
volume = {67},
number = {5},
pages = {279-287},
pmid = {42184295},
issn = {2737-5935},
mesh = {Humans ; *Translational Research, Biomedical ; Probiotics/therapeutic use ; *Microbiota ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Ecology ; },
abstract = {The human microbiome has emerged as a central focus of biomedical research, driven by interest in its translational potential for chronic diseases. Although compelling associations link microbial alterations to gastrointestinal, metabolic, neuropsychiatric and systemic conditions, successful clinical translation remains limited. This perspective contends that the principal barrier is not biological relevance but the application of reductionist thinking to an inherently complex ecological system, compounded by an incomplete understanding of causality. This review examines the gradient of causal confidence across gut-organ axes, from established roles in digestive disorders to less established distal associations, as well as highlights the epistemological challenges underlying microbiome research. A critical appraisal of current strategies, including probiotics, live biotherapeutics and faecal microbiota transplantation, suggests that progress requires ecological reasoning, causal rigour and systems-level integration. Moving from association to intervention demands approaches that account for host-microbiome complexity rather than oversimplified microbial targeting.},
}

Humans
*Translational Research, Biomedical
Probiotics/therapeutic use
*Microbiota
Fecal Microbiota Transplantation
*Gastrointestinal Microbiome
Ecology

@article {pmid42184718,
year = {2026},
author = {El-Sehrawy, AAMA and Soleimani Samarkhazan, H},
title = {The silent pharmacist: Harnessing the gut microbiome to improve therapy in hematologic malignancies.},
journal = {Translational oncology},
volume = {70},
number = {},
pages = {102833},
doi = {10.1016/j.tranon.2026.102833},
pmid = {42184718},
issn = {1936-5233},
abstract = {The gut microbiome, a complex ecosystem of microorganisms, is now recognized as a key determinant of drug efficacy and toxicity, giving rise to the field of pharmacomicrobiomics. This review decodes the profound influence of the gut microbiome on treatment outcomes for hematologic malignancies. We explore the tripartite mechanistic pathways through which gut microbes act: the direct enzymatic biotransformation of chemotherapeutic agents, the indirect immunomodulation of systemic and anti-tumor responses, and the preservation of mucosal barrier integrity to prevent devastating complications like graft-versus-host disease (GVHD). The manuscript details how the microbiome interacts with specific drug classes, from conventional chemotherapies like cyclophosphamide to cutting-edge immunotherapies like immune checkpoint inhibitors and CAR-T cells, shaping their clinical success. Furthermore, we discuss the translational potential of targeting this "silent pharmacist" through fecal microbiota transplantation, next-generation probiotics, and dietary interventions. Finally, we highlight the main translational opportunities, current limitations, and future clinical priorities for integrating microbiome science into hematology, paving the way for more personalized and improved cancer care.},
}

@article {pmid41850660,
year = {2026},
author = {Baca, A and Félix, J and Díaz-Del Cerro, E and Yépez-Notario, C and Requena, T and Martínez de Toda, I and De la Fuente, M},
title = {Gut microbiota transfer from old mice accelerates aging in adults.},
journal = {Mechanisms of ageing and development},
volume = {231},
number = {},
pages = {112177},
doi = {10.1016/j.mad.2026.112177},
pmid = {41850660},
issn = {1872-6216},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Aging/physiology ; Female ; *Longevity ; Oxidative Stress ; Feces/microbiology ; *Fecal Microbiota Transplantation ; Behavior, Animal ; },
abstract = {The gut microbiota communicates with the homeostatic systems (nervous, immune, and endocrine). As we age, there is an increase in oxidative stress, which can deteriorate these systems, the microbiota, and the communication between them. It has been suggested that the microbiota influence the aging process, though its specific effects remain unclear. This study aimed to assess the impact of transferring microbiota from old to adult mice on behavioral, immune, and redox parameters, as well as their rate of aging and longevity. Adult female mice were divided into three groups (N = 10/group): old microbiota (received 200 μL of old mice feces resuspended in PBS/3 days week/2 weeks, after a previous intestinal lavage with polyethylene glycol), adult microbiota (received adult mouse feces following the same procedure), and control (no manipulation). Feces were collected after treatment for microbiota and short-chain fatty acid analyses. After microbiota transfer, behavioral tests were performed, and peritoneal leukocytes were extracted to analyze immune and redox parameters, and to quantify biological age. These parameters were re-evaluated in old age, and the animals' longevity was recorded. The results showed that old microbiota group was characterized by the increase of Akkermansia, Anaerostipes, Dubosiella, and Ruminococcus, among others. In addition, the group displayed elevated levels of anxiety, impaired immune function, and increased oxidative-inflammatory stress, effects that continued into old age. These changes translated into higher biological age and lower longevity. In conclusion, microbiota transfer from old to adult mice disrupts neuroimmune homeostasis, increases oxidative-inflammatory stress and accelerates aging process, reducing longevity.},
}

Animals
*Gastrointestinal Microbiome/physiology
Mice
*Aging/physiology
Female
*Longevity
Oxidative Stress
Feces/microbiology
*Fecal Microbiota Transplantation
Behavior, Animal

@article {pmid42174754,
year = {2026},
author = {Chen, Y and Zhao, J and Zhao, J and Chen, Q and Dong, S and Jia, S and Zhao, Y and Hao, D and Yin, Y and Lin, S and Chen, Y and Zhuang, Y and Peng, H},
title = {Effects of fecal microbiota transplantation and probiotics on the gut microbiome in antibiotic-treated septic patients: A pilot randomized controlled trial.},
journal = {Virulence},
volume = {17},
number = {1},
pages = {2668764},
doi = {10.1080/21505594.2026.2668764},
pmid = {42174754},
issn = {2150-5608},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Probiotics/administration & dosage/therapeutic use ; *Fecal Microbiota Transplantation ; Pilot Projects ; Male ; Middle Aged ; Female ; *Sepsis/therapy/microbiology/drug therapy ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; Aged ; Prospective Studies ; Critical Illness ; Dysbiosis/therapy ; Treatment Outcome ; Feces/microbiology ; Adult ; RNA, Ribosomal, 16S/genetics ; },
abstract = {Broad-spectrum antibiotics, essential for sepsis management in critically ill patients, cause significant gut dysbiosis. Restoring gut microbiota may improve outcomes, but the efficacy of interventions like fecal microbiota transplantation (FMT) and probiotics in this setting remains underexplored. This study aims to evaluate the feasibility and potential efficacy of FMT versus probiotics on gut microbiome restoration and inflammatory markers in critically ill, antibiotic-treated sepsis patients. In this single-center, prospective, exploratory pilot RCT, 40 sepsis patients were were randomized 2:1:1 to: Control (n = 20, antibiotics treatment), Probiotics (n = 10, antibiotics treatment combined one week of probiotics), and FMT (n = 10, antibiotics treatment combined one week of FMT) groups. Gut microbiota composition was analyzed using 16S rDNA sequencing, and clinical inflammatory markers were assessed at baseline, one week, and two weeks post-treatment. FMT significantly mitigated antibiotic-induced reductions in microbial diversity. At 2 weeks, the FMT group exhibited higher alpha-diversity (Chao1 index, p = 0.0125; Shannon/Simpson trends p = 0.06) compared to Control and Probiotics groups. FMT increased beneficial Bacteroides abundance and reduced Enterobacteriaceae. BugBase analysis revealed FMT significantly lowered pathogenic potential of gut microbiota (p = 0.021). Donor-recipient analysis showed FMT shifted recipient microbiomes toward donor enterotype. This study provides preliminary evidence that FMT, but not the probiotic regimen, effectively restores gut microbiome diversity and composition, reduces pathogenic potential, and may improve clinical outcomes in critically ill sepsis patients after broad-spectrum antibiotics. This study was registered on ClinicalTrials.gov (NCT05578196).},
}

Humans
*Gastrointestinal Microbiome/drug effects
*Probiotics/administration & dosage/therapeutic use
*Fecal Microbiota Transplantation
Pilot Projects
Male
Middle Aged
Female
*Sepsis/therapy/microbiology/drug therapy
*Anti-Bacterial Agents/therapeutic use/adverse effects
Aged
Prospective Studies
Critical Illness
Dysbiosis/therapy
Treatment Outcome
Feces/microbiology
Adult
RNA, Ribosomal, 16S/genetics

@article {pmid42177552,
year = {2026},
author = {Zou, F and Wu, Z and Wang, S and Xu, M and Xia, P and Hu, Y and Fang, T and Hu, P and Huang, C and Deng, F},
title = {Microbiota-derived butyrate inhibits colonic epithelial pyroptosis and mitigates DSS-induced colitis via interacting with aryl hydrocarbon receptor.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08264-1},
pmid = {42177552},
issn = {1479-5876},
support = {82470586//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Intestinal barrier defects cause antigen translocation and immune dysregulation. The pyroptosis of colonic epithelial cells (CECs) disrupts the colonic barrier, and its inhibition might be a therapeutic approach for ulcerative colitis (UC), but the mechanisms are not fully understood.

METHODS: A DSS-induced UC model was established to assess the level of colonic epithelial cell pyroptosis. 16S rDNA sequencing and LC‒MS/MS were applied to screen potential candidate bacterial species and metabolites. The roles of target metabolites were evaluated in vivo using GSDMD-knockout mice. FHC cells treated with LPS + ATP were used as a cellular model of pyroptosis, and the underlying molecular mechanism was explored mainly by siRNA transfection and lentivirus infection.

RESULTS: We found that DSS-treated mice exhibited increased levels of pyroptosis in the colon. Fecal microbiota transplantation (FMT) significantly suppressed mucosal inflammation and CEC pyroptosis, accompanied by increased levels of butyrate-producing bacteria and butyrate in feces. Butyrate treatment alleviated DSS-induced colitis in mice. Moreover, GSDMD knockout mitigated DSS-induced colitis in mice, whereas a butyrate intervention failed to further ameliorate colitis in GSDMD-knockout mice. Mechanistically, we found that butyrate significantly inhibited LPS + ATP-induced pyroptosis by activating its receptor, aryl hydrocarbon receptor (AhR), in FHC cells, while silencing AhR suppressed this effect. The overexpression of cGAS in FHC increased the level of pyroptosis, whereas the administration of butyrate inhibited the activation of the cGAS-STING pathway. Treatment with a cGAS inhibitor significantly reversed the increase in pyroptosis caused by AhR knockdown in pyroptotic FHC cells.

CONCLUSIONS: Gut microbiota-derived butyrate levels were increased after FMT. Butyrate suppressed the proinflammatory cGAS-STING-NF-κB signaling axis via AhR to inhibit CEC pyroptosis and thereby alleviate UC.},
}

@article {pmid42177905,
year = {2026},
author = {Liu, T and Wang, H and Lu, D and Yan, C and Hang, F and Ma, B and Meng, X},
title = {Emodin inhibits the formation of gallstones by affecting the intestinal flora and expression of hepatic HIF1α.},
journal = {International immunopharmacology},
volume = {183},
number = {},
pages = {116878},
doi = {10.1016/j.intimp.2026.116878},
pmid = {42177905},
issn = {1878-1705},
abstract = {BACKGROUND: Gallstone disease is a prevalent digestive disorder worldwide; however, current therapeutic approaches remain limited. Emodin, a natural anthraquinone compound, exerts diverse biological effects including anti-inflammatory activity and metabolic regulation. To elucidate the mechanism by which emodin inhibits gallstone formation, we conducted in vivo experiments, multi-omics analysis, and network pharmacology.

METHODS: Six-week-old C57BL/6 mice were used to establish an in vivo model with emodin intervention. Fecal microbiota transplantation (FMT), 16S rRNA gene sequencing, and serum metabolomics sequencing were employed to investigate the effects of emodin on gut microbiota and serum metabolites. Network pharmacology was applied to predict the regulatory effects of emodin on liver-related genes, which were further verified by fundamental experiments. The correlations between gut microbiota, serum metabolites, and liver genes were explored. Statistical analysis was performed using GraphPad Prism 9.0.

RESULTS: The medium dose of emodin (30 mg/kg) showed the optimal inhibitory effect on gallstones formation. Emodin reshaped the intestinal flora structure in mice with gallstones and increased the abundance of Limosilactobacillus reuteri (L. reuteri) in vivo. By elevating serum tauroursodeoxycholic acid (TUDCA) levels in mice, emodin downregulated the expression of hepatic HIF1α and upregulated the expression of AQP8.

CONCLUSIONS: Emodin inhibited gallstone formation in mice through two complementary mechanisms. First, emodin modulated the gut microbiota to promote the proliferation of L. reuteri; second, it increased serum TUDCA levels, thereby regulating the HIF1α-AQP8 pathway to alleviate cholestasis. In addition, we speculate that L. reuteri may elevate serum TUDCA content via several indirect pathways.},
}

@article {pmid42178721,
year = {2026},
author = {Schulze, K and Goldschmidt, I and Melk, A and Boehne, M and Woltemate, S and Ballmaier, M and Kleiner, S and Lehmann, E and Kramer, M and Vital, M},
title = {Altered SIgA-targeting of gut microbiota is associated with long-term dysbiosis in pediatric solid organ transplant recipients.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2675078},
doi = {10.1080/19490976.2026.2675078},
pmid = {42178721},
issn = {1949-0984},
mesh = {Humans ; *Dysbiosis/microbiology/immunology/etiology ; *Gastrointestinal Microbiome ; Child ; Male ; Female ; *Immunoglobulin A, Secretory/immunology/genetics ; *Transplant Recipients ; Tacrolimus/adverse effects ; Bacteria/classification/genetics/isolation & purification ; Adolescent ; Immunosuppressive Agents/adverse effects/therapeutic use ; *Organ Transplantation/adverse effects ; Feces/microbiology ; Child, Preschool ; Liver Transplantation/adverse effects ; },
abstract = {The composition of the gut microbiota (GM) is altered in solid organ transplantation (SOT) recipients, where the degree of dysbiosis is associated with long-term survival and is believed to be influenced by immunosuppression therapy. At the interface stands secretory (S)IgA, however, little is known about its role in governing dysbiosis in the context of SOT. We performed quantitative metagenomic analyses of the GM accompanied by SIgA sequencing in 48 pediatric SOT recipients (age = 10.6 ± 4.7 y) receiving either heart (n = 11), kidney (n = 10) or liver transplantation (n = 27), and compared the results to age-matched healthy controls (HC, n = 16). We confirmed compositional and functional dysbiosis in SOT recipients, with the degree of dysbiosis being associated with tacrolimus (TAC) levels. Overall, SOT recipients exhibited higher SIgA levels than HC, along with an increased percentage of bacteria targeted and altered target spectra. Furthermore, altered SIgA responses were associated with the degree of dysbiosis. A mechanistic model connecting immunosuppression, GM composition and SIgA-targeting is proposed, suggesting that GM dysbiosis in SOT recipients is mediated by the immune system through the SIgA response; direct drug-mediated effects on fecal communities were not observed in in vitro experiments. Our study provides new insights into factors that contribute to persisting dysbiosis in SOT recipients.},
}

Humans
*Dysbiosis/microbiology/immunology/etiology
*Gastrointestinal Microbiome
Child
Male
Female
*Immunoglobulin A, Secretory/immunology/genetics
*Transplant Recipients
Tacrolimus/adverse effects
Bacteria/classification/genetics/isolation & purification
Adolescent
Immunosuppressive Agents/adverse effects/therapeutic use
*Organ Transplantation/adverse effects
Feces/microbiology
Child, Preschool
Liver Transplantation/adverse effects

@article {pmid42178957,
year = {2026},
author = {Ciesielski, P and Zaniewska, M and Waliszewski, M and Dziewa, N and Kołodziejczak, M},
title = {Treatment for full-thickness rectal prolapse using the abdominal access: An evaluation of 94 cases.},
journal = {Polski przeglad chirurgiczny},
volume = {98},
number = {2},
pages = {8-12},
doi = {10.5604/01.3001.0055.5841},
pmid = {42178957},
issn = {2299-2847},
mesh = {Humans ; *Rectal Prolapse/surgery ; Female ; Middle Aged ; Male ; Treatment Outcome ; Prospective Studies ; Adult ; Aged ; *Digestive System Surgical Procedures/methods ; Surgical Mesh ; },
abstract = {Introduction: Full-thickness rectal prolapse (FTRP) is a multifactorial disease that can be treated with different surgicaltechniques. There is still no standard surgical procedure, and the selection of the surgical technique is based on the individualassessment and the experience of the surgeon. The benefits to patients should focus on repair of bowel prolapse, reduction ofconstipation, and an improvement in pelvic floor muscle insufficiency.Aim: Aim of this study was to evaluate clinical and functional outcomes after abdominal surgery for FTRP in a prospective single- -center observational study.Materials and methods: Between 2016 and 2022, a total of 94 consecutive patients (46.2 18.2 years) underwent abdominal surgery due to FTRP using an abdominal approach. They were operated on with ventral mesh rectopexy (VMR) (55 pts.) or resection and suture rectopexy - Frykman-Goldberg procedure (FG) (39 pts.). Before and after the surgery, clinical and functional outcomes were measured. The follow-up period ranged from 1 to 6 years (mean: 26 months).Results: At last follow-up, constipation occurred in 27.6% of VMR and 31.3% of FG patients (p = 0.754; calculated among patients with available postoperative constipation status). The Wexner incontinence score was significantly better in the VMR group (1.0 2.1 vs. 3.6 5.0, p = 0.009). There were no differences in the EQ5D indices between the groups (1.7 2.0 vs. 2.4 2.8, p = 0.257).Conclusions: Both surgical procedures revealed comparable rates of recurrence and complications. While QoL was similarbetween groups, VMR yielded a significantly greater improvement in the Wexner incontinence score.},
}

Humans
*Rectal Prolapse/surgery
Female
Middle Aged
Male
Treatment Outcome
Prospective Studies
Adult
Aged
*Digestive System Surgical Procedures/methods
Surgical Mesh

@article {pmid42180552,
year = {2026},
author = {Chen, Y and Wei, X and Yi, X and Jiang, DS},
title = {Interactions between the gut microbiome and ferroptosis in degenerative diseases: Novel mechanisms and potential therapeutic strategies.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {5},
pages = {2711-2729},
pmid = {42180552},
issn = {2211-3835},
abstract = {Degenerative diseases are a group of medical conditions characterized by the progressive and irreversible deterioration of cells, tissues, and organs over time. Emerging evidence highlights the alteration and functions of the gut microbiome in the development of degenerative diseases. Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation, has been implicated as a pivotal factor in the regulatory effect of the gut microbiome on degenerative diseases. Moreover, gut metabolites, particularly short-chain fatty acids and trimethylamine N-oxide, are closely related to iron overload, redox imbalance, and lipid peroxidation. Recently, microbiome-based therapies, such as fecal microbiota transplantation, have been considered novel therapeutic strategies. In this review, we focus on degenerative diseases and explore the interactions between the gut microbiome and ferroptosis, aiming to provide new insights into the underlying mechanisms and clinical implications.},
}

@article {pmid42181429,
year = {2026},
author = {Lopez Garri, S and Lingier, P and Dassonville, M and Tulelli, B},
title = {Long-Term Quality of Life and Functional Outcomes in Patients With Anorectal Malformations: A Retrospective Multicenter Study in Brussels, Belgium.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e107561},
pmid = {42181429},
issn = {2168-8184},
abstract = {Introduction Anorectal malformations (ARMs) are congenital conditions requiring surgical correction. Despite surgical intervention, patients often experience persistent fecal and urinary dysfunction, significantly impacting their quality of life (QoL). This multicenter retrospective study aimed to assess QoL in ARM patients, identify factors influencing QoL deterioration, and propose improved management strategies. Methods We retrospectively analyzed data from 39 ARM patients who underwent surgery between 1999 and 2019 at two Belgian hospitals. Patients completed the Hirschsprung's Disease Anorectal Malformation Quality of Life Questionnaire (HAQL). We also reviewed their medical records. Descriptive statistical analysis was performed. Results At a median follow-up of 106 months, functional outcomes showed high rates of constipation (87%), fecal incontinence (54%), and fecal soiling (87%). Fecal incontinence was more prevalent in patients with bulbar rectourethral and recto-vesical fistulas. Postoperative complications occurred in 72% of patients, primarily in those with high ARMs, and correlated with increased constipation and abdominal pain. Management gaps were observed: only 47% of constipated patients and 56% of incontinent patients underwent anorectal manometry, and only 50% of constipated patients utilized physiotherapy. QoL assessment revealed persistent digestive functional disorders and physical symptoms across age groups, which improved with age. However, emotional and body image issues persisted into adulthood. Conclusion Patients with ARMs frequently experience significant functional digestive disorders and impaired QoL. Suboptimal management, particularly regarding the use of anorectal manometry and physiotherapy, contributes to these challenges. A long-term, multidisciplinary follow-up is crucial. This follow-up should include systematic dietary support, perineal rehabilitation, and targeted interventions guided by anorectal manometry to improve QoL in this population.},
}

@article {pmid42181890,
year = {2026},
author = {Gamal, NK and Fakhry, R and Hatem, Y and Rashed, E and Marzouk, R and Bukr, AKM and Akawi, N and George, MY},
title = {Neurodegeneration at the crossroads: the gut-brain axis and blood-brain barrier in Parkinson's disease - a review.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1813134},
pmid = {42181890},
issn = {1663-9812},
abstract = {Parkinson's disease (PD), which is one of the most common neurodegenerative illnesses, involves abnormal deposition of α-Synuclein and loss of dopaminergic neurons in the substantia nigra. Beyond this, there is increasing evidence that the gut-brain axis (GBA) and blood-brain barrier (BBB) interfere in disease initiation and progression. Dysbiosis of the gut microbiota affects the intestine and the BBB, allowing microbial metabolites and proinflammatory mediators to enter the CNS, causing neuroinflammation and neurodegeneration. Studies show that α-Synuclein pathology can originate in the gut and reach the brain via the vagus nerve. This review summarizes the connections among GBA, BBB, and PD, focusing on oxidative damage, inflammatory cascades, decreased expression of tight junction proteins, and signaling pathways such as TLR4/MyD88/NF-κB. In addition, we discuss therapeutic strategies that target the microbiota-BBB axis, such as probiotics, fecal microbiota transplantation, natural compounds (e.g., piperine, anethole, polymannuronic acid, Paeonia lactiflora), and stem cell therapy, which have demonstrated neuroprotective potential in animal models. Overall, the literature emphasizes the importance of restoring gut homeostasis and BBB integrity, and suggests that getting this axis right may offer novel opportunities for PD treatment. Future research is crucial to validate the efficacy of this approach clinically and to develop tailored therapies to prevent or delay PD progression.},
}

@article {pmid42182017,
year = {2026},
author = {Li, J and Qiu, X},
title = {Neurodevelopmental disorders and the gut microbiome: insights into ADHD and tic disorders.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1779746},
pmid = {42182017},
issn = {1664-302X},
abstract = {This review examines the relationship between tic disorders (TD), attention deficit hyperactivity disorder (ADHD), and the gut microbiota within the framework of the gut-brain axis. We summarize current evidence on the clinical characteristics and neurobiological features of TD and ADHD, and discuss how genetic susceptibility, environmental exposures, and dietary factors may interact with gut microbial composition. We further review studies comparing the gut microbiota of affected individuals and healthy controls, with attention to recurrent taxa-level findings, functional hypotheses, and emerging microbiome-targeted interventions such as probiotics and fecal microbiota transplantation. Importantly, most available human studies remain associative rather than mechanistic, and cross-study comparability is limited by heterogeneity in sequencing approaches, cohort characteristics, medication exposure, and dietary control. Overall, current findings support the gut microbiota as a relevant component of neurodevelopmental disorders such as ADHD and TD, while highlighting the need for larger longitudinal and mechanistic studies to clarify causality and therapeutic potential.},
}

@article {pmid42182071,
year = {2026},
author = {Qin, R and Yu, P and Wang, H and Zhou, J and Gong, R and Duan, Y and Jia, H and Xie, M and Zhou, Y and Hu, J},
title = {Gut-bone axis crosstalk: Microbiota-driven immune-metabolic-neural networks in bone disorders and precision interventions.},
journal = {Journal of orthopaedic translation},
volume = {58},
number = {},
pages = {101126},
pmid = {42182071},
issn = {2214-031X},
abstract = {UNLABELLED: The gut microbiota regulates bone metabolism via a complex gut-bone axis involving short-chain fatty acids (SCFAs), immune modulation, and neuroendocrine signals. However, the precise mechanisms remain unclear, and microbiota-targeted interventions (probiotics, prebiotics, fecal microbiota transplantation) are not yet optimized for clinical use. This review systematically synthesizes the immune-metabolic-neural interaction network within the gut-bone axis, highlighting non-linear crosstalk among SCFAs, bile acids, tryptophan derivatives, immune cells (macrophages, Treg/Th17), and vagus nerve signaling. We critically assess translational hurdles, including heterogeneous study designs, confounding factors, and lack of causal evidence. Based on this network perspective, we propose a framework for future research that prioritizes multi-omics approaches, stratified interventions, and rigorous trials. This synthesis advances understanding of how gut dysbiosis drives bone disorders and paves the way for precision skeletal medicine.

This review identifies microbial markers for risk stratification of bone metabolic disorders and discusses SCFA-based strategies and fecal microbiota transplantation (FMT) in conditions including osteoporosis, impaired fracture healing, rheumatoid arthritis, and glucocorticoid-associated osteonecrosis. It provides testable hypotheses for large-scale randomized controlled trials (RCTs), directly supporting translation of microbiome research into clinical practice for bone disorders.},
}

@article {pmid42182110,
year = {2026},
author = {Zhang, Z and Holton, M and Ferrer, DM and Tripp, AD and Richter, A and Dixit, PD and Urtecho, G},
title = {Metagenome-scale Modeling to Assess Microbiome Metabolic Complementarity for Precision Microbiota Transplantation Therapies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.15.725570},
pmid = {42182110},
issn = {2692-8205},
abstract = {Fecal microbiota transplantation (FMT) holds therapeutic promise beyond recurrent Clostridioides difficile infection, but clinical outcomes remain unpredictable, in part because existing computational models do not fully capture the metabolic compatibility between donor and recipient communities. Here, we present a metagenome-scale metabolic modeling framework that quantifies metabolic niche complementarity between donor and recipient microbiomes to predict transplantation outcomes. Using MICOM-derived community metabolic models, we show that donor taxa whose metabolic flux profiles are more dissimilar from the recipient community engraft at significantly higher rates in both murine and human FMT cohorts. In a human IBS trial, metabolic models accurately predicted post-FMT community composition via leave-one-out cross-validation and recapitulated disease-associated alterations in short-chain fatty acid, sulfur, and gas metabolism. We then performed 2,548 in silico FMT simulations between IBS-D/M patients and donors from the OpenBiome biobank to demonstrate a platform for personalized donor screening. This screen identified super-donors characterized by high taxonomic diversity, broad metabolic niche coverage, and community interaction networks dominated by cross-feeding rather than competition, as quantified by a flux-derived ecological network balance index that strongly predicted engraftment potential. This framework provides a mechanistic, scalable tool for rational donor-recipient matching that could guide personalized microbiome-based therapies.},
}

@article {pmid42183070,
year = {2026},
author = {Dou, M and Xu, J and Ye, X and Liu, J and Shi, L},
title = {Fecal Microbiota Transplantation From Healthy Donors Reduces Glycemic Variability in Streptozotocin-Induced Diabetic Rats via Enhanced Hepatic Glycogen Synthesis.},
journal = {International journal of endocrinology},
volume = {2026},
number = {},
pages = {8852077},
pmid = {42183070},
issn = {1687-8337},
abstract = {BACKGROUND: Blood glucose fluctuations in patients with brittle diabetes have been a problem for clinicians. A recent study found that transplanting the intestinal flora of healthy people to patients with brittle diabetes can improve their blood glucose fluctuations. However, the underlying mechanism remains unclear.

METHODS: Streptozotocin-induced diabetic rats were assigned to receive fecal microbiota transplantation (FMT) from healthy donors or to remain untreated, while normal rats received FMT from brittle diabetes donors or remained untreated. Groups included the normal control group (NC group), the diabetic group (DM group), normal rats with FMT from brittle diabetic patients (NC-DMFMT group), and diabetic rats with FMT from normal individuals (DM-NCFMT group). Blood glucose variability, rat liver glucokinase, and glycogen levels, as well as intestinal short-chain fatty acid content, were detected in each group of rats. Gut microbiota composition was analyzed using 16S rDNA sequencing.

RESULTS: Compared with the standard deviation of blood glucose (SDBG) (1.664 ± 0.427 mmol/L) in the NC group, that of the DM group (6.879 ± 1.475 mmol/L) was higher. However, the DM-NCFMT group reduced SDBG (4.387 ± 0.619 mmol/L) vs. the DM group (p < 0.05). Hepatic glycogen (27.57 ± 5.254 mg/L) was lower in the DM group than in the NC group (55.48 ± 9.467 mg/L) but increased in the DM-NCFMT group (37.59 ± 1.283 mg/L) vs. the DM group. The abundance of Bifidobacteria in the DM group was decreased compared to that in the NC group. In contrast, Bifidobacterium abundance in the DM-NCFMT group increased after standard human flora transplants (p < 0.05). Correlation and stepwise regression analysis indicated that Bifidobacteria reduced SDBG partly by promoting hepatic glycogen synthesis, with an effect share of 23.01%.

CONCLUSION: Normal individual fecal microbiota transplantation improves glucose variability in DM rats, potentially mediated by enhanced hepatic glycogen synthesis.},
}

@article {pmid42173875,
year = {2026},
author = {Nie, X and Li, Q and Tao, Z and Xu, Y and Li, B and Xie, J and Nie, S},
title = {Faecalibacterium prausnitzii-derived extracellular vesicles ameliorate experimental colitis through regulating barrier immunity and gut microbiota.},
journal = {NPJ science of food},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41538-026-00897-2},
pmid = {42173875},
issn = {2396-8370},
support = {SKLF-ZZB-202543//State Key Laboratory of Food Science and Resources, Nanchang University/ ; 20242BAB21031//Natural Science Foundation of Jiangxi/ ; 20232BCD44003//Technological Project of Jiangxi Province/ ; },
abstract = {Ulcerative colitis (UC) is closely linked to intestinal barrier dysfunction and gut dysbiosis. Bacterial extracellular vesicles (bEVs) act as key mediators of bacteria-host crosstalk, with great potential in regulating host health. Recent studies have shown that EVs derived from gut commensal bacteria offer therapeutic advantages in treating UC. Herein, we explored the therapeutic effect of Faecalibacterium prausnitzii-derived EVs (PEVs) in DSS-induced colitis mice. Results showed PEVs significantly improved intestinal barrier damage, restored Th17/Treg balance and alleviated gut dysbiosis. Further fecal microbiota transplantation (FMT) confirmed that feces from PEVs-treated mice transferred beneficial effects to recipient colitis mice. Collectively, our findings indicate that commensal gut microbiota-derived nanovesicles have the potential to serve as candidates for UC treatment.},
}

@article {pmid42173912,
year = {2026},
author = {Huang, Y and Hu, Y and Zhao, Y and Li, Y and Liu, Y and Wang, M and Wang, Q and Hu, H},
title = {Ulcerative colitis-driven gut dysbiosis exacerbates periodontal bone loss through the gut-oral axis /Th17/Treg imbalance.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-026-01015-6},
pmid = {42173912},
issn = {2055-5008},
support = {gzwkj2025-445//the Science and Technology Fund of Guizhou Provincial Health Commission(gzwkj2025-445)/ ; QKHJC-MS[2026]895//Guizhou Provincial Science and Technology Programme/ ; 17zy-002//Outstanding Young Talent Project of Zunyi Medical University/ ; HZ[2024]340//the Zunyi Science and Technology Program/ ; },
abstract = {Ulcerative colitis (UC) and periodontitis, both microbial dysbiosis-driven chronic inflammatory disorders, coexist and mutually exacerbate, but the causal mechanisms remain unclear. Using ligature-induced periodontitis plus DSS-colitis mice, we found UC doubles alveolar bone loss, heightens systemic inflammation, oxidative stress, and osteoclastogenesis. 16S rRNA and LC-MS metabolomics showed UC enriches oral pathogens, depletes gut Firmicutes, expands Bacteroides, and correlates with suppressed amino-acid/bile-acid biosynthesis. Fecal microbiota transplantation (FMT) from DSS donors into antibiotic-pretreated periodontitis-prone mice replicated aggravated bone loss, systemic inflammation, gut-barrier leakage, and Th17/Treg imbalance, while healthy-donor FMT protected. GC-MS revealed 35-60% reductions in acetate, propionate, and butyrate; keystone taxa Parabacteroides and Muribaculum inversely correlated with SCFAs and host inflammatory genes. Collectively, UC-driven gut dysbiosis is a transmissible causal factor that simultaneously remodels oral and intestinal biofilms, erodes epithelial barriers, and amplifies osteoclastic bone resorption. SCFAs-producing microbes or supplementation may be potential therapeutics for UC-associated periodontitis patients.},
}

@article {pmid42172084,
year = {2026},
author = {Oliveira, JM and Luxo, C and Matos, AM},
title = {Human Polyomaviruses of Clinical Relevance: Modes of Transmission and Associated Pathologies.},
journal = {Reviews in medical virology},
volume = {36},
number = {3},
pages = {e70166},
doi = {10.1002/rmv.70166},
pmid = {42172084},
issn = {1099-1654},
support = {//Fundação para a Ciência e a Tecnologia/ ; },
mesh = {Humans ; *Polyomavirus Infections/transmission/virology/pathology/diagnosis ; *Polyomavirus/pathogenicity/classification/genetics/physiology/isolation & purification ; Seroepidemiologic Studies ; Clinical Relevance ; },
abstract = {Polyomaviruses are non-enveloped viruses with double-stranded circular DNA genome. Currently, 13 members of the Polyomaviridae family have been classified as human polyomavirus (HPyVs). Despite high seroprevalence values have been reported for the majority of the HPyVs worldwide, the main mode of transmission remains to be elucidated, and simple and common routes, such as faecal-oral and respiratory have been suggested. In general, HPyVs are responsible for asymptomatic primary infection, followed by asymptomatic lifelong persistent infection. In situations of severe immunosuppression, viral reactivation of some HPyVs may occur and result in the development of associated clinical manifestations. JCPyV is the causative agent of Progressive Multifocal Leukoencephalopathy, BKPyV is associated with nephropathy among kidney transplant recipients, MCPyV with Merkel Cell Carcinoma and TSPyV with Trichodysplasia spinulosa. The association of certain HPyVs with severe diseases, in addition to the high seroprevalence of the majority of HPyVs, emphasises the need to address various knowledge gaps that still exists in the natural history of these viruses, including the transmission routes and the pathogenic mechanisms. The present review summarises current information on HPyV transmission routes and associated diseases, including diagnosis and available treatment options, highlighting the need for further studies.},
}

Humans
*Polyomavirus Infections/transmission/virology/pathology/diagnosis
*Polyomavirus/pathogenicity/classification/genetics/physiology/isolation & purification
Seroepidemiologic Studies
Clinical Relevance

@article {pmid42172181,
year = {2026},
author = {Gomes, JV and Ribeiro, SPO and Nascimento, GMCD and Santos, DOD and Paula, DJG and Lima, SCS and Simão, TA},
title = {The human microbiome in cancer: Not just a sidekick anymore.},
journal = {Genetics and molecular biology},
volume = {49Suppl 1},
number = {Suppl 1},
pages = {e20250236},
pmid = {42172181},
issn = {1415-4757},
abstract = {The human microbiome is increasingly recognized as a dynamic element in cancer biology. Studies across breast, prostate, lung, colorectal, and cervical tumors reveal that microbial communities influence carcinogenesis, immune regulation, and treatment outcomes. When the balance of these microorganisms is altered, inflammation becomes chronic, metabolism is disrupted, and signaling pathways such as NF-κB, IL6-STAT3, and β-catenin are activated. Bacterial metabolites and genotoxins, including colibactin and bile acids, may damage DNA and reshape the epigenetic landscape. Distinct microbial profiles have been linked to prognosis and to patient responses to chemotherapy and immunotherapy. The presence of beneficial taxa, such as Akkermansia muciniphila and Ruminococcus, has been associated with improved response to immune checkpoint inhibitors. At the same time, antibiotic-induced depletion of gut microbiome can reduce therapeutic efficacy. Strategies that help restore microbial balance, including probiotics, dietary interventions, and fecal microbiota transplantation, are being explored as complementary therapies. Although methodological differences and contamination remain challenges, the growing body of evidence indicates that the microbiome is a measurable and modifiable component of tumor ecosystems with strong potential for diagnostic, prognostic, and therapeutic applications in precision oncology.},
}

@article {pmid42172659,
year = {2026},
author = {Liu, C and Yin, X and Yuan, X},
title = {Gut microbiota dysbiosis and osteoporosis: pathogenesis and novel intervention strategies.},
journal = {Future microbiology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17460913.2026.2678122},
pmid = {42172659},
issn = {1746-0921},
abstract = {Osteoporosis represents a major global public health challenge, with current pharmacological treatment often limited by substantial side effects. Recent research identifies the gut-bone axis as a key regulatory pathway linking gut microbiota to bone metabolic homeostasis. This review synthesizes findings from PubMed, Web of Science, and Scopus (up to March 2026) to elucidate how gut microbiota dysbiosis drives osteoporosis pathogenesis through interconnected mechanisms: aberrant immune modulation, altered microbial metabolites, impaired nutrient absorption, endocrine disruption, and systemic inflammation stemming from intestinal barrier failure. Consequently, these pathways disrupt the delicate balance of bone remodeling. Based on these insights, we outline novel microbiota-targeted therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation, natural bioactive compounds, traditional Chinese medicine, and nanomaterials. These interventions aim to prevent and manage osteoporosis by reshaping the intestinal microecology via multi-target modulation. Future endeavors should prioritize in-depth mechanistic exploration, personalized precision interventions, and enhanced clinical translation to integrate these strategies into comprehensive osteoporosis care frameworks.},
}

@article {pmid42172982,
year = {2026},
author = {Yan, S and Zhang, Y and Fan, Q and Jia, W and Dai, Y and Li, X and Lu, S and Sheng, Y and Sun, S and Lin, R and Tang, Y and Zhao, C},
title = {Evodiamine targets ZO-1 to ameliorate cholestatic liver disease: Intestinal homeostasis as the core mediator of gut-liver axis repair and bile acid metabolism remodeling.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {157},
number = {},
pages = {158288},
doi = {10.1016/j.phymed.2026.158288},
pmid = {42172982},
issn = {1618-095X},
abstract = {BACKGROUND: Cholestatic liver disease (CLD) is a complex and multifactorial chronic disorder that requires a systematic and integrative management. Evodiamine (EVO), a natural alkaloid derived from Evodiae Fructus, has demonstrated significant therapeutic potential in ameliorating digestive diseases. However, the beneficial effects of EVO on CLD and the underlying mechanisms remain poorly understood.

OBJECTIVE: This study aims to elucidate the mechanisms through which EVO modulates the progression of CLD, with a particular focus on the regulation of gut-liver axis homeostasis.

METHODS: The therapeutic efficacy of EVO in bile duct ligation (BDL)- and α-naphthyl isothiocyanate (ANIT)-induced CLD rat models was systematically evaluated. An integrative approach combining network pharmacology with multi-omics analyses (transcriptomic, metagenomic sequencing, targeted bile acid metabolomics) was employed to identify significantly altered molecular networks. Fecal microbiota transplantation (FMT) was conducted to validate the functional role of gut microbiota in the hepato-intestinal protective effects. Direct molecular targets as well as the functional validation were confirmed through molecular docking, pull-down assays, surface plasmon resonance and cellular thermal shift assay.

RESULTS: EVO achieved significant synchronous hepato-intestine protection in both CLD rats: it markedly ameliorated hepatic injury and hepatic fibrosis, downregulated pro-inflammatory cytokine levels, while preserving intestinal barrier integrity and alleviating intestinal inflammation. Mechanistically, EVO exerted these protective effects by directly targeting the tight junction protein ZO-1 and enhancing its expression and stability. Furthermore, EVO restored intestinal microbial homeostasis, corrected dysregulated BA metabolism-specifically normalizing deoxycholic acid (DCA) levels. FMT experiments demonstrated that the synchronous hepato-intestinal beneficial effects of EVO were partially mediated by gut microbiota.

CONCLUSION: EVO exerts a protective effect against CLD by directly targeting ZO-1 to strengthen intestinal barrier function, thereby restoring gut microbial balance and rebalancing BAs metabolism (especially DCA levels) in the gut-liver axis. This study uncovers a novel ZO-1-dependent mechanism of EVO in CLD, highlighting EVO as a promising candidate for the treatment of CLD and providing new insights into gut-liver axis-targeted therapies.},
}

@article {pmid42168337,
year = {2026},
author = {Tao, M and Liu, Y and Guo, H and Gao, S and Wang, Y and Yan, X and Zhu, Y},
title = {The role of the gut microbiota in radiation enteritis: from mechanistic insights to therapeutic applications.},
journal = {Communications biology},
volume = {9},
number = {1},
pages = {},
pmid = {42168337},
issn = {2399-3642},
support = {BK20250559//Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)/ ; 82403008//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024M762749//China Postdoctoral Science Foundation/ ; },
mesh = {*Gastrointestinal Microbiome/radiation effects ; Humans ; *Enteritis/microbiology/therapy/etiology ; *Radiation Injuries/microbiology/therapy ; Dysbiosis/microbiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Radiotherapy/adverse effects ; },
abstract = {Radiation enteritis (RE) is a severe adverse reaction after abdominal and pelvic radiotherapy, with a complicated pathogenesis and no effective treatment. Although gut microbiota dysbiosis was reported to play a critical role in RE, related molecular characteristics and intervention strategies have not been extensively summarized. In this review, the mechanisms of RE, including injury to intestinal stem cells, damage to the vascular endothelium, reshaped immune microenvironment, and mucosal barrier dysfunction, are discussed. In addition, radiation-induced gut microbiota dysbiosis is characterized by decreased abundance of beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium bifidum, and increased abundance of detrimental bacteria such as Escherichia-Shigella and Enterococcus. Beneficial and detrimental bacteria affect the development of RE by regulating inflammatory signaling pathways such as NF-κB and JAK/STAT3, and through their metabolites such as bile acids and short-chain fatty acids. Accordingly, several microbiome-targeted therapeutic strategies, including antibiotic administration, dietary interventions, fecal microbiota transplantation, probiotic administration and engineered bacteria, have been developed to mitigate RE. However, some challenges still remain for these therapeutic strategies. The goal of this review is to highlight the crucial role of gut microbiota dysbiosis in the pathogenesis of RE, thereby accelerating the development of individualized microbial therapies against this disease.},
}

*Gastrointestinal Microbiome/radiation effects
Humans
*Enteritis/microbiology/therapy/etiology
*Radiation Injuries/microbiology/therapy
Dysbiosis/microbiology
Animals
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Radiotherapy/adverse effects

@article {pmid42168694,
year = {2026},
author = {Sahu, P and Satapathy, T},
title = {The Gut-Liver Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Mechanisms, Microbiome Interactions and Therapeutic Targets.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {42168694},
issn = {1867-1314},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multifactorial condition in which the gut-liver axis plays a central pathogenic role. While a large body of literature has described associations between gut microbiota alterations and MASLD, a critical synthesis of the mechanistic pathways linking microbial activity to liver injury remains lacking. This review specifically focuses on gut-derived microbial metabolites as key mediators of disease progression. We examine how short-chain fatty acids, bile acids, lipopolysaccharide (LPS), trimethylamine-N-oxide (TMAO) and microbially derived ethanol influence hepatic lipid metabolism, inflammation and fibrogenesis through defined molecular pathways, including FXR signaling, TLR4 activation and immune-metabolic crosstalk. Importantly, we highlight inconsistencies in human microbiome studies, limitations in establishing causality and the challenges in translating preclinical findings into effective therapies. Although microbiome-targeted interventions such as probiotics, bile acid modulators and fecal microbiota transplantation show promise, their clinical efficacy remains variable due to interindividual heterogeneity and lack of mechanistic precision.By integrating current mechanistic evidence with translational insights, this review identifies critical knowledge gaps and proposes future directions for metabolite-focused therapeutic strategies. A more precise understanding of gut-derived signaling pathways will be essential to move from associative microbiome research toward targeted and personalized interventions in MASLD.},
}

@article {pmid42168704,
year = {2026},
author = {Zhang, X and Mallick, H and Rahnavard, A},
title = {Meta-analytic microbiome target discovery for immune checkpoint inhibitor response in advanced melanoma.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {42168704},
issn = {2730-664X},
support = {2109688//National Science Foundation (NSF)/ ; 2109688//National Science Foundation (NSF)/ ; },
abstract = {BACKGROUND: Immune checkpoint inhibitors have transformed melanoma therapy, yet only a subset of patients achieve durable responses. Gut microbes have been linked to response, but reported biomarkers vary across studies. We aim to identify reproducible microbial features and test their generalizability across cohorts and treatment settings.

METHODS: We reprocessed stool metagenomic sequencing data from 15 melanoma cohorts (763 samples from 484 individuals), including 12 cohorts treated with immune checkpoint inhibitors alone and 3 trials combining immune checkpoint inhibitors with fecal microbiota transplantation. Using a unified analysis pipeline, we profiled microbial species, metabolic pathways, and biosynthetic gene clusters, and analyzed their associations with treatment response using Tweedie regression, random-effects meta-analysis, and multimodal integration with leave-one-dataset-out validation.

RESULTS: Here, we show that responders in immune checkpoint inhibitor-only cohorts are enriched for several short-chain fatty acid-producing commensals, whereas non-responders show higher abundance of taxa associated with disrupted gut communities. In fecal microbiota transplantation plus immune checkpoint inhibitor trials, response associates with distinct communities and shifts in amino-acid, nucleotide and cofactor metabolism. Across cohorts, multiview prediction models repeatedly select gene clusters linked to antimicrobial peptides and surface polysaccharides, but cross-study discrimination remains modest.

CONCLUSIONS: Microbiome signatures of response are treatment-context dependent and are not captured by a single universal species. These harmonized findings prioritize microbial taxa and functions for mechanistic studies and future microbiome-informed interventions.},
}

@article {pmid42169007,
year = {2026},
author = {Lu, Y and Rong, X and Wei, L and Yang, J and Zhang, K and Tan, Y and Zhao, N and He, X and Lu, C and Li, L},
title = {Baicalein mitigates epithelial barrier impairment and microbiota dysbiosis in allergic asthmatic mice via the gut‑lung axis.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {42169007},
issn = {1749-8546},
support = {ZB2025013//The Fundamental Research Funds for the Central public welfare research institutes/ ; CI2023C065YLL//Scientific and technological innovation project of China Academy of Chinese Medical Sciences/ ; 102160222020040009016, 160202001000210007//Scientific Research Facility Special Foundation for Operation and Maintenance/ ; },
abstract = {BACKGROUND: Allergic asthma (AA) may result in repeated episodes of chest constriction and coughing. In its most serious manifestations, it can cause death by asphyxiation. Currently, no efficacious therapeutic interventions exist to avert or counteract these serious outcomes. Baicalein (BAI) is a core quality marker of the traditional Chinese medicine Scutellaria baicalensis, but the mechanism of its oral action remains unclear.

OBJECTIVE: Assess the therapeutic efficacy of BAI in AA mice models and investigate its mechanism of action.

STUDY DESIGN AND METHODS: Evaluate the efficacy of BAI on ovalbumin-induced AA mice. To assess alterations in the pulmonary and gut microbial communities, 16S rRNA sequencing was employed. The integrity and restoration of the lung and intestinal epithelial lining were evaluated via immunohistochemistry. Furthermore, gas chromatography-mass spectrometry quantified fecal levels of short-chain fatty acids (SCFAs) in AA mice, and flow cytometry was used to analyze the content of ILC2 cells in colon tissue. Finally, the role of beneficial bacteria and their metabolites in inhibiting AA was further confirmed through fecal microbiota transplantation (FMT).

RESULTS: Oral BAI effectively alleviated AA-related lung epithelial damage and microbiota dysbiosis, while elevating the production of the tight junction proteins. Moreover, BAI mitigated colonic epithelial damage, inhibited ILC2s activation in the colon, enriched the abundance of gut probiotics capable of producing SCFAs, especially Akkermansia muciniphila (A. muciniphila), and increased the content of SCFAs such as propionic acid in feces. The FMT experiment conducted after gavage with broad-spectrum antibiotics confirmed that BAI mediated reversal of microbial dysbiosis plays a key role in the treatment of AA, significantly increasing the expression of GPR41 mRNA in colon tissue and inhibiting the activation of ILC2s.

CONCLUSION: The potential prebiotic BAI mitigates AA via targeting A. muciniphila and its metabolites, which consequently inhibits epithelial damage and type 2 immune activation.},
}

@article {pmid42171840,
year = {2026},
author = {Yu, Y and Tian, M and Sun, S and Wang, H and Qin, M and Gao, Y and Jia, X and Gao, Q and Jiang, F},
title = {Fecal Microbiota Transplantation from Exercise-Preconditioned Mice Attenuates Post-stroke Cognitive Impairment by Preserving Gut and Blood-Brain Barrier Integrity.},
journal = {Neurochemical research},
volume = {51},
number = {3},
pages = {},
pmid = {42171840},
issn = {1573-6903},
support = {2108085MH252//Natural Science Foundation of Anhui Province/ ; 2023AH040288//Natural Science Research Program for Universities in Anhui Province/ ; 2024byfy004//the Science and Technology Programme of Bengbu Medical University/ ; No. 82070265//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Blood-Brain Barrier/metabolism ; *Fecal Microbiota Transplantation/methods ; *Physical Conditioning, Animal/physiology ; *Cognitive Dysfunction/therapy/etiology ; *Gastrointestinal Microbiome/physiology ; Male ; Mice ; Mice, Inbred C57BL ; *Stroke/complications ; },
abstract = {Exercise preconditioning reduces post-stroke cognitive impairment (PSCI), but the contribution of the gut microbiota (GM) to barrier protection remains unclear. We examined whether exercise-preconditioned GM contributes to PSCI improvement and preservation of gut and blood-brain barrier (BBB) integrity. Mice were preconditioned with 4 weeks of voluntary wheel running prior to stroke induction. We assessed cognitive function, GM composition, fecal short-chain fatty acid (SCFA) levels, inflammation, and gut-blood-brain barrier (BBB) integrity. Then, we used fecal microbiota transplantation (FMT) to evaluate how GM contributes to the benefits of voluntary exercise. Our results showed that exercise remodeled the GM composition and elevated SCFAs levels. Also, exercise suppressed systemic, colonic, and neuroinflammation, enhanced the barrier-related protein (Occludin, Claudin-5, and ZO-1) levels, maintained barrier integrity, and alleviated cognitive dysfunction after ischemic stroke. FMT from exercised mice partially reproduced the cognitive and anti-inflammatory benefits. SCFA levels were associated with reduced inflammatory markers and increased expression of barrier-related proteins. The findings suggest that exercise preconditioning is associated with coordinated preservation of gut and BBB integrity and improved cognition after stroke. Moreover, FMT from exercised mice conferred partial protection against PSCI.},
}

Animals
*Blood-Brain Barrier/metabolism
*Fecal Microbiota Transplantation/methods
*Physical Conditioning, Animal/physiology
*Cognitive Dysfunction/therapy/etiology
*Gastrointestinal Microbiome/physiology
Male
Mice
Mice, Inbred C57BL
*Stroke/complications

@article {pmid42171841,
year = {2026},
author = {Gómez-Montañez, E and Rojas-Salazar, YL and Rojas-Salazar, JG},
title = {Microbiome in Gastrointestinal Tumors: Implications in Oncogenesis and Therapeutic Response : Microbiome in Gastrointestinal Tumors.},
journal = {Current oncology reports},
volume = {28},
number = {1},
pages = {},
pmid = {42171841},
issn = {1534-6269},
mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/therapy/pathology ; *Gastrointestinal Microbiome ; *Carcinogenesis ; *Dysbiosis/microbiology ; Tumor Microenvironment ; *Microbiota ; },
abstract = {PURPOSE OF REVIEW: To provide an updated overview of the role of the human microbiome in the initiation, progression, and therapeutic response of gastrointestinal tumors, emphasizing molecular, immunological, and metabolic mechanisms, as well as its potential as a target for novel therapeutic strategies.

RECENT FINDINGS: Emerging evidence demonstrates that microbiome dysbiosis contributes to carcinogenesis across gastrointestinal malignancies, including colorectal, gastric, hepatic, and pancreatic cancers. Microbial-derived metabolites, such as short-chain fatty acids and secondary bile acids, modulate key signaling pathways involved in cell proliferation, apoptosis, and genomic stability. In addition, the microbiome influences the tumor microenvironment and immune responses, shaping variability in treatment outcomes. Both preclinical and clinical studies have shown that microbiome composition affects the efficacy and toxicity of chemotherapy and immunotherapy. Notably, specific microbial signatures are being explored as non-invasive biomarkers for early detection and prognostic stratification, while microbiome modulation strategies, such as diet, probiotics, antibiotics, and fecal microbiota transplantation, have demonstrated potential to enhance therapeutic response. The bidirectional interaction between the microbiome and the host plays a central role in gastrointestinal tumorigenesis and treatment response. Although this field holds significant promise for precision oncology, its clinical translation remains limited by interindividual variability, methodological heterogeneity, and insufficient longitudinal evidence. Future efforts should focus on standardization, validation of microbiome-based biomarkers, and integration of multi-omics and artificial intelligence approaches to enable clinically actionable applications.},
}

Humans
*Gastrointestinal Neoplasms/microbiology/therapy/pathology
*Gastrointestinal Microbiome
*Carcinogenesis
*Dysbiosis/microbiology
Tumor Microenvironment
*Microbiota

@article {pmid42171928,
year = {2026},
author = {Bi, Q and Zhang, L and Wan, H and Zhang, J},
title = {Harnessing the gut microbiota to enhance immune checkpoint inhibitor efficacy: from mechanistic insights to clinical translation.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42171928},
issn = {1573-4978},
support = {HUST: 32500006//Fundamental Research Funds for the Central Universities/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Animals ; *Neoplasms/immunology/therapy/microbiology/drug therapy ; Tumor Microenvironment/immunology/drug effects ; Fecal Microbiota Transplantation/methods ; Immunotherapy/methods ; Translational Research, Biomedical ; },
abstract = {Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 pathways have revolutionized cancer therapy, yet their efficacy is frequently limited by primary or secondary resistance. Emerging evidence underscores the gut microbiota as a decisive regulator of ICI therapeutic outcomes. This review systematically delineates the multi-dimensional mechanisms through which the microbiota modulates anti-tumor immunity, specifically focusing on the molecular remodeling of immune signaling by microbial metabolites such as short-chain fatty acids (SCFAs) and bile acids, cross-reactive immunity driven by antigenic molecular mimicry, and the spatial restructuring of the tumor microenvironment mediated by the gut-tumor axis. Clinically, fecal microbiota transplantation (FMT) has demonstrated the potential to reverse ICI resistance, while the development of live biotherapeutic products (LBPs) and precise prebiotic combinations offers a standardized path for niche-specific intervention. Despite these advances, critical challenges persist, including the biological mismatch in cross-species animal models, the context-dependency arising from individualized microbial signatures, and the cognitive gap in the temporal dynamics of microbe-drug interactions. Deciphering the non-linear correlation between microbial succession and host immune response will be essential for integrating microbiota-driven strategies into personalized oncology frameworks.},
}

Humans
*Gastrointestinal Microbiome/immunology/drug effects
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Animals
*Neoplasms/immunology/therapy/microbiology/drug therapy
Tumor Microenvironment/immunology/drug effects
Fecal Microbiota Transplantation/methods
Immunotherapy/methods
Translational Research, Biomedical

@article {pmid42159494,
year = {2026},
author = {García-Vidal, C and Gallardo-Pizarro, A and Aiello, TF and Kwon, M and Salavert, M and Pitart, C and Suarez-Lledó, M and Soriano, A and Mensa, J},
title = {Antibiotic therapy in febrile neutropenia in haematological patients: current considerations and future challenges.},
journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia},
volume = {},
number = {},
pages = {},
doi = {10.37201/req/165.2026},
pmid = {42159494},
issn = {1988-9518},
abstract = {The management of febrile neutropenia (FN) in oncohematological patients is undergoing a paradigm shift driven by a deeper understanding of patients' pathophysiological heterogeneity, the increasing speed and accuracy of microbiological diagnostics, the emergence of new antibiotics, and the incorporation of predictive artificial intelligence (AI) as a tool to support clinical decision-making. Our objective is to provide an updated and comprehensive overview of the factors influencing antibiotic treatment in FN. We propose that its management should be based on three essential pillars. First, accurate risk stratification for bacterial infection. Second, ensuring that patients receive appropriate empirical antibiotic therapy, tailoring the initial choice according to the results of surveillance cultures from oropharyngeal and/or fecal microbiota. Finally, prioritizing antibiotic choices that preserve intestinal microbiota eubiosis as much as possible. Reducing colonization and overgrowth of facultative aerobic/anaerobic flora (Enterobacteriaceae, non-fermenting Gram-negative bacilli, and Enterococcus spp.) while preserving strict anaerobic flora decreases the risk of bacterial translocation and complications such as graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or loss of CAR-T functionality. This decision model, grounded in objective criteria, aims to balance the need for effective empirical coverage with responsible antibiotic use.},
}

@article {pmid42159959,
year = {2026},
author = {Zhang, Z and Jiang, F and Li, Z and Lin, L and Qi, B and Han, D and Ran, C and Mao, S and Wang, J and Zhou, Z and Wang, M and Li, J and Wang, G and Kang, S and Zhang, T},
title = {Animal gut microbes and microbiomes in the 21st century and beyond.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {42159959},
issn = {1869-1889},
abstract = {Animal gut microbiomes-comprising bacteria, archaea, fungi, viruses, and protozoa-are fundamental to host evolution, physiology, and ecosystem resilience. This review synthesizes 21st-century advances in their diversity, spatiotemporal dynamics, and functional roles across the animal kingdom. Although high-throughput metagenomics has transformed the field, major biases remain: most studies still focus on domesticated vertebrates and fecal samples, leaving substantial "microbial dark matter" in wild hosts, invertebrates, and non-bacterial domains unexplored. We highlight how gut microbiomes mediate adaptation to environmental extremes, including hypoxia, temperature stress, and toxins, and how industrialization disrupts these communities, contributing to biodiversity loss and disease risk. We further integrate eco-evolutionary theory, multi-omics, and spatial modeling to clarify cross-kingdom interactions and functional networks. Finally, we discuss translational applications-including probiotics, fecal microbiota transplantation (FMT), phage therapy, and synthetic consortia-and emphasize the need for global collaborative initiatives, artificial intelligence (AI)-driven discovery, and standardized databases to unlock the full potential of animal gut microbiomes for biodiversity conservation, climate resilience, and planetary health in the coming decades.},
}

@article {pmid42160026,
year = {2026},
author = {Zhao, M and Hou, J and Wang, J and Zhu, X and Zou, A and Wang, Y and Liu, Z and Xianyu, Y},
title = {Food-Derived Biohybrid Probiotic Extracellular Vesicles for Synergistic Therapy of Inflammatory Bowel Disease.},
journal = {Small (Weinheim an der Bergstrasse, Germany)},
volume = {},
number = {},
pages = {e73858},
doi = {10.1002/smll.73858},
pmid = {42160026},
issn = {1613-6829},
support = {LZ26B050002//Natural Science Foundation of Zhejiang Province/ ; 2025C02124//"Pioneer" and "Leading Goose" R&D Program of Zhejiang/ ; 82470544//National Natural Science Foundation of China/ ; 2026YFE0214400//National Key Research and Development Program of China/ ; },
abstract = {Inflammatory bowel disease is a chronic gastrointestinal disorder characterized by persistent intestinal inflammation, microbiota dysbiosis, and impaired mucosal barrier function. Conventional treatments, including pharmacological agents, biologics, and fecal microbiota transplantation, are limited by adverse effects, immune suppression, recurrence, and low patient acceptance. In this study, food-derived probiotic extracellular vesicles (EVs) from Lactiplantibacillus plantarum with dietary polysaccharide (chitosan) and polyphenol (tannic acid) are developed as a synergistic therapeutic strategy for inflammatory bowel disease. The engineered biohybrid with dual-functional coating confers gastrointestinal stability and colon-targeted delivery, while scavenging reactive oxygen species and preserving the intrinsic microbiota-regulating properties of probiotic EVs. Multi-omics approach reveals correlations among microbial community shifts, short-chain fatty acids, oxidative stress modulation, inflammatory cytokine profiles, and disease severity indices. This work provides a promising approach and reveals the synergistic mechanisms of engineered probiotic EVs in reshaping gut microbiota, modulating metabolic networks, and improving the inflammatory microenvironment for the treatment of inflammatory bowel disease.},
}

@article {pmid42161263,
year = {2026},
author = {Ni, M and Junker, K and Liu, Y and Fan, Y and Li, Y and Qiao, W and Zhang, XS and Ksiezarek, M and Mead, EA and Tourancheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Davey, LE and Fang, G},
title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.},
journal = {Cell host & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2026.04.019},
pmid = {42161263},
issn = {1934-6069},
abstract = {The human microbiome continuously adapts to variations in diet and host physiology. Epigenetic phase variation (ePV) mediated by bacterial DNA methylation can generate phenotypic heterogeneity within clonal populations. ePVs have been characterized in human pathogens, but their roles in commensals remain unclear. Here, we cataloged ePVs in infant and adult gut microbiomes, revealing genome-wide and site-specific ePV in response to antibiotics and fecal microbiota transplantation. Long-read metagenomics revealed genome-wide ePV mediated by structural variations of DNA methyltransferases. Analysis of public short-read metagenomic datasets further revealed a high prevalence of genome-wide ePVs in the human microbiome. Site-specific ePVs were identified and associated with antibiotics or probiotic engraftment. Focusing on an Akkermansia muciniphila isolate, we find a specific ePV regulating mucC, a gene of unknown function but whose heterologous expression enhances bacterial tolerance to antibiotics via a bet-hedging strategy. Thus, epigenetic modifications are used by gut bacteria to adapt to fluctuating environments.},
}

@article {pmid42162499,
year = {2026},
author = {Gu, R and Li, J and Qi, J and Sun, R and Wu, H and Jin, B},
title = {Odoribacter laneus protects intestinal barrier by bile acid-FXR axis in acute pancreatitis.},
journal = {AMB Express},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13568-026-02071-z},
pmid = {42162499},
issn = {2191-0855},
support = {2023YP44//the Cultivation Foundation of The Second Hospital of Shandong University/ ; },
abstract = {Odoribacter laneus (O. laneus) is a promising probiotic. Acute pancreatitis (AP) is an acute abodominal disease accompanied by intestinal barrier dysfunction and gut dysbiosis. However, the effects of O. laneus in AP remain unexplored. We established AP model of C57BL/6 mice. Western blotting and immunohistofluorescence were used to detect the expression of intestinal tight junction proteins and FXR/NLRP3 pathway. The changes of gut microbiota and bile acids (BAs) were analyzed by 16 S rRNA gene and targeted metabolomics sequencing. The fecal microbiota transplantation (FMT) was used to investigate the role of gut microbiota in O. laneus treatment. O. laneus effectively reduced systemic inflammation, pancreatic damage, and intestinal barrier dysfunction in AP mice. We observed significant enrichment of pathogens along with depletion of second BAs (7-KDA) in AP mice, and these alterations were reversed by O. laneus. FMT experiment showed that the protective roles of O. laneus depended on gut microbiota. O. laneus ameliorated AP via activating intestinal FXR and inhibiting NLRP3 inflammasome in vivo. In vitro and vivo studies showed that 7-KDA protected AP. Taken together, O. laneus could mitigate AP-induced intestinal barrier dysfunction by reversing the disorderd gut microbiota, BAs metabolism, and modulating FXR/NLRP3 pathway.},
}