@article {pmid41253270,
year = {2025},
author = {Ding, L and Xu, JY and Zhang, LL and Liu, Y and Gu, KT and Liang, YZ and Hidayat, K and Wan, Z and Chen, GC and Qin, LQ},
title = {Lactoferrin alleviates non-alcoholic steatohepatitis via remodeling gut microbiota to regulate serotonin-related pathways.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.11.034},
pmid = {41253270},
issn = {2090-1224},
abstract = {INTRODUCTION: Lactoferrin (LF), a multifunctional glycoprotein, has been implicated in the regulation of glucose and lipid metabolism.

OBJECTIVES AND METHODS: This study employed in vivo and in vitro models to investigate the direct effects of LF on non-alcoholic steatohepatitis (NASH) and to elucidate its underlying mechanisms.

RESULTS: LF intervention alleviated hepatic lipid metabolic disorders and liver injury in high-fat, high-cholesterol cholate-containing diet (HFCCD)-fed mice by mitigating oxidative stress, suppressing the inflammatory cGAS/STING pathway, and reducing M1 proinflammatory macrophage polarization. These effects were validated in free fatty acid (FFA)-treated HepG2 cells and AML12 cells. Furthermore, LF ameliorated HFCCD-induced gut microbiota dysbiosis and increased short-chain fatty acid levels. The critical role of gut microbiota in mediating the hepatoprotective effects of LF was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation. Mechanistically, LF modulated gut-liver serotonin signaling and promoted fatty acid β-oxidation through the HTR2A-PPARα-CPT-1A pathway, an effect abolished by the HTR2A agonist DOI. In a co-culture system, LF treatment of the Caco-2/HT29 monolayer alleviated lipid accumulation and regulated the HTR2A-PPARα-CPT-1A pathway in FFA-treated HepG2 cells.

CONCLUSIONS: These findings indicate that LF attenuates NASH by remodeling gut microbiota to modulate microbiota-derived serotonin signaling and enhance fatty acid oxidation.},
}

@article {pmid41252333,
year = {2025},
author = {Bahji, A and Brietzke, E and Cooke, NCA and Clement, F and Frey, BN and Hofmeister, M and Kennedy, SH and Lam, R and Milev, R and Moinul, D and Parikh, SV and Patten, S and Ravindran, A and Rosenblat, JD and Samaan, Z and Schaffer, A and Saleem, A and Beaulieu, S and Tourjman, V and Van Ameringen, M and Vigod, S and Yatham, L and Taylor, V and , },
title = {The Canadian Network for Mood and Anxiety Treatments Task Force Recommendations for the Use of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplants in Adults With Major Depressive Disorder: Recommandations du Groupe de travail du Réseau canadien pour le traitement des troubles de l'humeur et de l'anxiété (Canadian Network for Mood and Anxiety Treatments, CANMAT) concernant l'utilisation des probiotiques, des prébiotiques, des symbiotiques et de la transplantation de microbiote fécal chez les adultes atteints de trouble dépressif majeur.},
journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie},
volume = {},
number = {},
pages = {7067437251394363},
doi = {10.1177/07067437251394363},
pmid = {41252333},
issn = {1497-0015},
abstract = {BackgroundApproximately one-third of adults with major depressive disorder (MDD) experience limited response or intolerable side effects with existing pharmacotherapies. As such, innovative treatments targeting novel biological pathways are under investigation. One promising area of research is the gut microbiome and its influence on mood through the microbiota-gut-brain axis. Clinical studies have begun evaluating microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) as potential treatments for MDD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to evaluate the evidence for microbiome-targeted interventions in adults with MDD and to provide updated clinical recommendations.MethodsA systematic review of randomized controlled trials (RCTs) and meta-analyses was conducted, assessing interventions such as probiotics, prebiotics, synbiotics, and FMT in adults with MDD. The CANMAT methodology was used to determine levels of evidence and treatment line recommendations, which were presented in a question-and-answer format.ResultsTwenty-three RCTs and eight meta-analyses were included. Probiotics have been the most extensively studied and have demonstrated modest improvements in depressive symptoms, particularly when used in an adjunctive manner. However, recent high-quality trials yielded mixed results. Evidence for prebiotics and FMT was limited and inconclusive, while synbiotics were assessed in only one small RCT. Most interventions were well tolerated, with few serious adverse events.ConclusionsProbiotics may be cautiously considered as third-line adjunctive treatments for MDD, though findings remain inconsistent. There is currently insufficient evidence to recommend prebiotics, synbiotics, or FMT in clinical practice. Further large-scale, well-controlled trials are needed to clarify efficacy, safety, and optimal patient subgroups.},
}

@article {pmid41252206,
year = {2025},
author = {Moreau, GB and Tian, J and Natale, NR and Naz, F and Young, MK and Nayak, U and Tanyüksel, M and Rigo, I and Madden, GR and Abhyankar, MM and Hagspiel, N and Brovero, S and Worthington, M and Behm, B and Marie, C and Petri, WA and Ramakrishnan, G},
title = {FMT promotes type 2 mucosal immune responses with colonic epithelium proliferation in recurrent CDI patients.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.195678},
pmid = {41252206},
issn = {2379-3708},
abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.

METHODS: We report the results of a clinical trial of subjects undergoing FMT therapy for rCDI (n=16), analyzing colon biopsies, plasma, peripheral blood mononuclear cells, and stool at the time of FMT and two-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with rCDI patients. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.

RESULTS: No subjects experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared to both pre-FMT and healthy control biopsies, inhibiting genes associated with pro-inflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.

CONCLUSIONS: We conclude that FMT promotes proliferation of the colonic epithelium in rCDI patients, which may drive regeneration and protect against subsequent CDI.

CLINICALTRIALS: gov NCT02797288.

FUNDING: NIH grants R01 AI152477, R01 AI124214, and K23 AI163368.},
}

@article {pmid41250648,
year = {2025},
author = {Yang, J and Tan, H and Peng, X and Nie, S},
title = {Tamarind Seed-Derived Xyloglucan Attenuates Insulin Resistance in Mice through Gut Microbiota.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c07829},
pmid = {41250648},
issn = {1520-5118},
abstract = {Xyloglucan (XG), a plant polysaccharide abundant in tamarind seeds, is FDA-approved for use as a food additive, stabilizer, thickener, or gelling agent. While its structural properties have been well-studied, its physiological effects remain unclear. This study employed a high-fat diet-induced insulin resistance mouse model to evaluate the effects of XG on metabolic disturbances, combining 16S rRNA sequencing and metabolomics to determine the role of gut microbiota. Results showed that XG intervention in HFD-fed mice improved glucose tolerance and liver function and reduced inflammation and oxidative stress, linked to altered carnitine and tryptophan metabolism. Gut microbiota analysis revealed selective enrichment of Bifidobacterium. Crucially, the benefit of XG was transferable via fecal microbiota transplantation but was abolished by antibiotic-induced microbiota depletion. This study demonstrates that tamarind seed-derived xyloglucan alleviates metabolic disturbances via a gut-microbiota-dependent mechanism, supporting its potential probiotic role in functional foods.},
}

@article {pmid41250124,
year = {2025},
author = {Huang, SW and Lin, CR and Chang, YH and Ni, YH and Chen, HL and Liu, HH},
title = {Cross-country multi-modal evidence links Aspergillus to biliary atresia.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {94},
pmid = {41250124},
issn = {1757-4749},
abstract = {BACKGROUND: Biliary atresia (BA) is the leading cause of pediatric liver transplantation. It is characterized by progressive extrahepatic bile duct obstruction in young infants. Inspired by the success of antifungal treatment in a newborn with BA-related obstructive cholangitis, we explored a potential link between BA and fungi, particularly Aspergillus. Fecal DNA was analyzed using 18S ribosomal sequencing and validated with a published fecal metagenomic dataset. Epidemiological data from the UK, Taiwan, and Japan were also examined.

RESULTS: Gut Aspergillus was exclusively detected in BA cases, suggesting it may be a potential trigger. Independent fecal metagenomic data from China and epidemiological correlations further supported this hypothesis. In the UK, BA presentations strongly correlated (r = 0.98, 95% CI [0.36, 1.0], p = 0.02) with Aspergillosis, but not with Candidiasis, during the COVID-19 lockdown. In Taiwan, a decade of data showed BA incidence was significantly associated (r = 0.78, 95% CI [0.29, 0.94], p = 0.01) with yearly Aspergillus-positive isolates among cancer-adjusted hospital admissions. In Japan, BA cases over 25 years correlated significantly (r = 0.85, 95% CI [0.37, 0.97], p = 0.01) with visceral Aspergillus burdens in autopsied cases, but not with other fungal infections.

CONCLUSIONS: The resolution of obstructive cholangitis in the antifungal-treated index case, together with multi-modal, cross-country evidence, highlights a potential link between gut Aspergillus and BA. Although limited by small sample size, retrospective design, and lack of mechanistic validation, the study may still be interpreted as hypothesis-generating and underscores the need for prospective studies to validate and extend these observations.},
}

@article {pmid41249722,
year = {2025},
author = {Xu, N and He, Y and Yang, G and Huang, X},
title = {Exploring the Role of Gut Microbiota in Chronic Spontaneous Urticaria: Mechanisms and Potential Therapeutic Implications.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41249722},
issn = {1867-1314},
support = {no. 82103751//National Natural Science Foundation of China/ ; },
abstract = {Gut microbiota dysbiosis has emerged as a significant factor in the pathogenesis of chronic spontaneous urticaria (CSU), a condition characterized by immune dysregulation and skin inflammation. This review summarizes the current understanding of the role of gut microbiota in CSU pathogenesis, highlighting the alterations in microbial composition and function, the mechanisms by which dysbiosis triggers systemic inflammation and skin mast cell activation, and the impact of microbial metabolites. We critically evaluate the potential of gut microbiota-targeted therapies, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), as novel treatment strategies for CSU. Despite the evident promise of these approaches, significant challenges persist, including the necessity for personalized interventions, the collection of long-term efficacy and safety data, and a more profound understanding of the complex interplay between the gut and skin. Future research endeavors must prioritize the execution of clinical trials that evaluate the efficacy of gut microbiota modulation in CSU patients and the identification of biomarkers that can effectively predict treatment response.},
}

@article {pmid41248567,
year = {2025},
author = {Huang, F and Zhang, L and Cheng, S and Zhang, Z and Xiang, Q and Xiao, Z},
title = {Banxia Baizhu Tianma Decoction improves posterior circulation ischemia vertigo in rats via gut microbiota and TLR4-NF-κB-MyD88 pathway.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157539},
doi = {10.1016/j.phymed.2025.157539},
pmid = {41248567},
issn = {1618-095X},
abstract = {BACKGROUND: Posterior circulation ischemia vertigo (PCIV) frequently presents with vestibular dysfunction in patients suffering from posterior circulation stroke. The conventional approaches often fail to address PCIV's complex pathophysiology, which involves neuroimmune dysregulation, hemodynamic abnormalities, and gut-brain axis disruption. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine, is employed in treating PCIV and vasogenic vertigo, but the mechanisms underlying its efficacy require further elucidation.

PURPOSE: This study examines the therapeutic mechanisms and efficacy of BBTD for PCIV, particularly focusing on its impacts on neuroinflammation, gut microbiota communities, and gut barrier using a rat model of PCIV.

METHODS: The chemical and bioactive constituents of BBTD were profiled using ULPLC-Q Exactive-Orbitrap-MS. The PCIV model was employed and treated with BBTD for 7 days. Neurological score was measured with balance beam test; cerebellar pathology was assessed by H&E and Nissl staining. The TTC staining was used to measure cerebral infarct volume. The levels of IL-6, IL-1β, and TNF-α in serum and cerebellar tissue was analyzed by ELISA. Its mechanisms were investigated by 16S rRNA sequencing, antibiotic antagonistic and fecal microbiota transplantation (FMT) experiments. Significant alterations in gut microbiota and their detailed mechanisms were identified. Intestinal barrier integrity was assessed by AB-PAS staining, tight junction proteins (MUC2, occludin, claudin-1, ZO-1), and colonic inflammatory cytokine levels. The levels of short-chain fatty acids in the cecal contents and cerebellar tissues of our experimental rats using gas chromatography-mass spectrometry (GC-MS).

RESULTS: Our findings demonstrated that BBTD significantly improved neurological function, ameliorates cerebral ischemia, and alleviated neuroinflammation in rats. Moreover, BBTD significantly modulated the diversity and composition of the gut microbiota, elevating Lactobacillus and Akkermansia, while reducing Clostridiales and Ruminococcaceae. The further antibiotic depletion and FMT experiments confirmed that gut microbiota was essential for BBTD-induced neuroinflammation and gut barrier protection in PCIV. BBTD ameliorated intestinal damage by enhancing acidic mucins and tight junction protein expression. BBTD treatment markedly increased the concentrations of propionic acid in intestinal fecal content and cerebellar tissue. Mechanistically, BBTD ameliorates ischemia-induced neuroinflammation and neuronal injury by modulating the TLR4-NF-κB-MyD88 pathway via the gut-brain axis.

CONCLUSION: BBTD ameliorates PCIV through gut-brain axis modulation, restoring gut barrier-microbiota balance and suppressing TLR4-NF-κB-MyD88 signaling. BBTD treatment and FMT may serve as an effective therapeutic strategy for mitigating posterior circulation ischemia progression.},
}

@article {pmid41247394,
year = {2025},
author = {Wu, Y and Chan, SSM and Leung, PWL and Lo, HHL and Ho, SWS and Mo, FYM and Ho, CSW and Shea, CKS and Su, Q and Leung, TF and Chan, FKL and Ng, SC and Wong, OWH},
title = {The Mediating Role of Eating Behaviors Between Autistic Symptoms and Dietary Issues Among Chinese Children With Autism.},
journal = {Journal of autism and developmental disorders},
volume = {},
number = {},
pages = {},
pmid = {41247394},
issn = {1573-3432},
support = {InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China//InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China//InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; PF22-77807//The Hong Kong PhD Fellowship Scheme/ ; },
abstract = {PURPOSE: Eating and dietary challenges are common among children with autism, but their associations with clinical symptoms remain unclear. This study aims to describe dietary issues, including nutritional problems and overexposures to food additives in autistic children, and their associations with clinical symptoms.

METHODS: This case-control study involved 836 children (469 with autism and 367 without autism; mean age = 8.3 years) profiled on autistic symptoms, eating behaviors, and dietary patterns with parent-reported questionnaires. Nutritional insufficiencies, dietary quality and food additives exposures were compared using regression models adjusted for age and sex. Multivariate logistics or linear regression models were used to identify clinical symptoms that predict dietary issues, with mediation analyses examining eating behaviors' roles.

RESULTS: Autistic children had lower protein intake, more vitamin and mineral insufficiencies, higher exposure to food additives, and poorer diet quality. They consumed fewer fruits/vegetables and more animal-based fats, with 38.2% exceeding 125% of the Estimated Energy Requirement (vs. 22.9% controls), suggesting energy-dense, ultra-processed food preferences. Diminished food enjoyment and increased food fussiness mediated between low social motivation and nutritional insufficiencies, as well as poorer diet quality. Further, difficulties with food responsiveness and emotional eating patterns mediated between more restricted and repetitive behaviors and higher exposures to emulsifiers/thickeners.

CONCLUSION: Autistic children, especially those with severe core symptoms, are susceptible to multifaceted dietary issues such as preference for low-quality food and nutrient deficiencies. It is crucial to implement personalized treatment strategies that target their specific eating behaviors to effectively address dietary challenges.},
}

@article {pmid41247324,
year = {2025},
author = {Weagley, JS and Cárdenas, LAC and Romani, A and Sullender, ME and Aggarwal, S and Makimaa, H and Hogarty, MP and Rodgers, R and Kennedy, EA and Foster, L and Schriefer, LA and Baldridge, MT},
title = {Differential Microbial Community Assembly Following Co-housing versus Microbiota Transplant.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wraf256},
pmid = {41247324},
issn = {1751-7370},
abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transfer of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of faecal or caecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, faecal transplantation, and caecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored bacterial and viral populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transfer-recipient control mice. Although all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. Overall, faecal and caecal transplant resulted in highly similar colonization processes with some minor variation in enrichment for two specific bacterial families. This study provides valuable insights into microbial ecology, as well as the dynamics underlying experimental microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transfer in mouse models.},
}

@article {pmid41247039,
year = {2025},
author = {Kelly, CR and Feuerstadt, P},
title = {Diagnosis and Management of C. difficile.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000003844},
pmid = {41247039},
issn = {1572-0241},
abstract = {Clostridioides difficile infection (CDI) is challenging to diagnose and treat. Recently published studies and clinical observations have improved our understanding around diagnostic testing and positioning of antibiotics and microbiota-based therapies. This review synthesizes current evidence and guidelines on CDI diagnosis, highlighting the limitations of individual tests and the value of algorithmic approaches. Treatment paradigms are discussed across the spectrum of disease severity, with vancomycin and fidaxomicin as first-line therapies and the diminishing role of metronidazole. For recurrent CDI, newer fecal microbiota-based therapies, including Fecal Microbiota, live-jslm (Rebyota, RBL) and Fecal Microbiota Spores, live-brpk (Vowst, VOS), are reviewed. The role of conventional fecal microbiota transplantation (FMT), particularly in fulminant CDI, is also addressed, including challenges resulting from FDA policies around stool bank material. We aim to clarify diagnostic and therapeutic approaches and optimize care for patients with CDI.},
}

@article {pmid41246810,
year = {2025},
author = {Tan, H and Chen, M and Yao, H and Li, S and Nie, S},
title = {Dominant Gut Commensals Enriched by Pectin with Low Esterification Degree Orchestrate the Amelioration of Acute Ulcerative Colitis.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c09097},
pmid = {41246810},
issn = {1520-5118},
abstract = {Dietary fiber's health benefits are increasingly recognized as microbiota-dependent, with effects influenced by fiber structure. We previously observed that low-esterified pectin provides superior protection against DSS-induced colitis compared to its high-esterified form, but the mechanism was unknown. This study investigated the microbiota-dependent pathway underlying low-esterified pectin's anticolitic effect using FMT. By evaluating three pectin-induced bacteria (Bifidobacterium longum NSP002, Bacteroides xylanisolvens NSP003, Enterococcus faecium NSP004) individually and in a consortium, we found that the consortium exerted a significantly stronger protective effect, suggesting synergistic interactions and highlighting its potential as an FMT alternative. Mechanistically, this protection may involve three axes: (1) Gut microbiome remodeling (reduced Akkermansia, increased Bacteroides, elevated propionic acid). (2) Intestinal homeostasis modulation (reduced mme/calprotectin expression, activated PI3K/calcium signaling). and (3) Systemic metabolic reprogramming (increased serum phenylethylamine, enriched phenylalanine metabolism). These findings support the clinical potential of pectin for optimizing enteral nutrition and using pectin-enriched microbiota consortia to target IBD pathogenesis.},
}

@article {pmid41246285,
year = {2025},
author = {Ahmed, N and Gaur, V and Kamle, M and Chauhan, A and Chauhan, R and Kumar, P and Singh, NA},
title = {Microbiome-based therapeutics for metabolic disorders: harnessing microbial intrusions for treatment.},
journal = {Frontiers in medical technology},
volume = {7},
number = {},
pages = {1695329},
doi = {10.3389/fmedt.2025.1695329},
pmid = {41246285},
issn = {2673-3129},
abstract = {The rising global rates of metabolic disorders, such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, call for new treatment methods beyond traditional drugs. The human gut microbiota, made up of trillions of microorganisms that plays a crucial role in maintaining metabolic balance through complex biochemical processes and interactions between hosts and microbes. Dysbiosis, which involves changes in microbial composition and a decrease in diversity, has become a major factor in metabolic problems. This disruption impacts the production of short-chain fatty acid, increase in permeability of intestine, and causes enduring low-grade inflammation. This review features into the potential of treatments based on microbiome for metabolic syndromes, focusing on probiotics, prebiotics, synbiotics, and postbiotics. It also encompasses innovative methods such as engineered microbial consortium, fecal microbiota transplantation (FMT), and vaginal microbiota transplantation (VMT). Probiotics show significant promise in improving blood sugar control and enhancing lipid levels. Prebiotics help bring about positive changes in microbial composition and the production of beneficial metabolites. Synbiotic combinations provide added benefits by helping good microbes thrive while supplying nutrients they can ferment. Postbiotics have recent research focus because they are safer, more stable, easier to store, and less likely to contribute to antibiotic resistance comparative to live probiotics. Even now there are substantial complications in translating microbiome research into standardized therapeutics despite of promising pre-clinical outcomes and some initial clinical data. These comprises individual variances, strain-specificity, dosage problems, regulation issues, and the necessity for personalised treatment strategies. Future success will depend upon personalized medicine, technological developments, and the incorporation of multi-omics strategy to generate metabolic health therapeutics depending on targeted microbiomes.},
}

@article {pmid41245267,
year = {2025},
author = {Makkar, SK and Bishnupuri, KS},
title = {The gut microbiome and gastrointestinal cancers: mechanisms, biomarkers and therapeutic opportunities.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1676796},
doi = {10.3389/fphys.2025.1676796},
pmid = {41245267},
issn = {1664-042X},
abstract = {Gastrointestinal (GI) cancers remain a leading global cause of cancer-related mortality, significantly impacting public health and healthcare systems worldwide. Emerging evidence underscores the critical role of gut microbiome dysbiosis-characterized by disrupted microbial diversity and function-in GI carcinogenesis. Utilizing recent advancements in multi-omics technologies and sophisticated computational biology, researchers have elucidated distinct microbial signatures associated with colorectal, gastric, hepatobiliary, pancreatic, and esophageal cancers. This review comprehensively analyzes the primary mechanisms through which gut microbes contribute to cancer development and progression, encompassing genotoxicity, chronic inflammation, metabolic dysregulation, epigenetic modifications, and immunomodulation. Moreover, we explore innovative microbiome-derived biomarkers for potential clinical applications, including early diagnosis, prognosis assessment, and therapeutic response prediction. The intricate interactions between microbiota and standard cancer therapies-chemotherapy, immunotherapy, and radiation therapy-are discussed, highlighting microbiome influences on therapeutic efficacy and adverse effect profiles. We also critically assess the impact of modifiable factors such as diet, medications, lifestyle, and environmental exposures on microbiome composition and cancer risk. The review evaluates emerging therapeutic interventions, including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation (FMT), and engineered live biotherapeutics. Despite notable advancements, significant hurdles remain, including clarifying causality, methodological standardization, and equitable global research representation. Addressing these challenges, we propose a strategic research agenda aimed at harnessing microbiome insights to advance precision oncology and improve GI cancer outcomes globally.},
}

@article {pmid41244880,
year = {2025},
author = {Bautista, J and Hidalgo-Tinoco, C and Di Capua Delgado, M and Viteri-Recalde, J and Guerra-Guerrero, A and López-Cortés, A},
title = {The gut-brain-circadian axis in anxiety and depression: a critical review.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1697200},
doi = {10.3389/fpsyt.2025.1697200},
pmid = {41244880},
issn = {1664-0640},
abstract = {Anxiety and depressive disorders rank among the most prevalent psychiatric conditions worldwide, yet remission rates remain unsatisfactory despite advances in pharmacological and psychotherapeutic interventions. The gut-brain axis has emerged as a transformative framework for understanding these disorders, emphasizing bidirectional communication between the central nervous system, the enteric nervous system, the endocrine and immune systems, and the gut microbiota. Preclinical studies demonstrate that germ-free or dysbiotic states exaggerate hypothalamic-pituitary-adrenal (HPA) reactivity, remodel synaptic plasticity, and induce anxiety- and depression-like behaviors, while fecal microbiota transplantation confirms the causal influence of microbial communities. Mechanistically, neural (e.g., vagal), endocrine (e.g., cortisol), immune (e.g., cytokine), and metabolic (e.g., short-chain fatty acids, tryptophan metabolites, bile acids) pathways converge to regulate mood and stress resilience. An underappreciated yet critical dimension of this model is circadian rhythmicity. Both host endocrine cycles and microbial communities exhibit diurnal oscillations that synchronize metabolism, immune activity, and neural signaling. Disruption of these rhythms, through factors such as sleep disturbance, irregular feeding, or shift work, alters microbial diversity, dampens metabolite oscillations, destabilizes HPA regulation, and enhances neuroinflammation, thereby amplifying vulnerability to psychiatric disorders. Collectively, evidence supports a model in which anxiety and depression are systemic conditions arising from integrated neural, immune, endocrine, metabolic, and circadian dysregulation, rather than isolated brain-based pathologies. This reconceptualization positions microbial taxa and metabolites as candidate biomarkers and therapeutic targets. Precision interventions, ranging from diet and psychobiotics to fecal microbiota transplantation, chrononutrition, and immune-modulatory strategies, offer promising avenues for personalized psychiatry.},
}

@article {pmid41244772,
year = {2025},
author = {Li, Q and Song, XC and Li, K and Wang, J},
title = {Gut-lung immunometabolic crosstalk in sepsis: from microbiota to respiratory failure.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1685044},
doi = {10.3389/fmed.2025.1685044},
pmid = {41244772},
issn = {2296-858X},
abstract = {Sepsis is a systemic immune-metabolic disorder syndrome caused by infection, in which gut microbiota dysbiosis plays a central role in the occurrence and development of multi-organ dysfunction. This paper systematically elaborates on the bidirectional regulatory mechanism of the "gut-lung axis" in sepsis. Gut microbiota dysregulation damages the gut barrier function, reduces the production of short-chain fatty acids (SCFAs), and increases endotoxin translocation. Subsequently, it activates alveolar macrophage polarization, promotes the formation of neutrophil extracellular traps (NETs), and leads to an imbalance in the Treg/Th17 cell ratio, ultimately exacerbating the pathological process of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Conversely, the pulmonary inflammatory response can also aggravate gut barrier damage through circulating inflammatory mediators, forming a vicious cycle. Mechanistically, HIF-1α, mTOR, and Sirtuins do not act in isolation. Instead, they jointly regulate the metabolic fate of immune cells through spatiotemporally dynamic interactions. During the evolution of sepsis, these signals exhibit opposite regulatory polarities during the hyper-inflammatory phase and the immunosuppressive phase, and mitochondrial dysfunction and oxidative stress further amplify the inflammatory cascade reaction. Preclinical research evidence shows that microbiota-based intervention measures (including probiotic preparations, fecal microbiota transplantation, and SCFA supplementation) and vagus nerve electrical stimulation can effectively alleviate sepsis-related lung injury and improve prognosis, but there is significant individual heterogeneity in their therapeutic effects. Future research should not be restricted to descriptive associations. Instead, it is essential to conduct in-depth analyses of the specific logic of the aforementioned signaling networks in terms of cell types, subcellular compartments, and disease course timings, and clarify their context-dependent controversies to promote the transformation of mechanistic understanding into precision treatment. Meanwhile, research efforts should focus on constructing a multi-omics dynamic biomarker system integrating metagenomics, metabolomics, and immunophenotyping analysis and designing clinical trials through precise patient stratification to facilitate the clinical translation of individualized treatment strategies based on gut-lung axis regulation.},
}

@article {pmid41243436,
year = {2025},
author = {Cen, Q and Cui, Y and Jin, J and Feng, J and Xin, Y and Zhang, Z and Li, J and Wang, J and Zhang, A},
title = {Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2576657},
doi = {10.1080/19490976.2025.2576657},
pmid = {41243436},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Multiple Sclerosis/metabolism/microbiology/therapy ; *Lipid Metabolism ; Animals ; },
abstract = {Dysregulation of the structure of the gut microbiota is closely linked to the risk of onset and progression of multiple sclerosis. The intricate interaction between the gut microbiota and lipid metabolism likely serves as a crucial pathway mediating this relationship: the gut microbiota directly or indirectly modifies lipid metabolism (including cholesterol, sphingolipids, phospholipids, and fatty acids) by controlling the production of specific metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, trimethylamine-N-oxide, and lipopolysaccharides), thereby impacting core pathological processes in multiple sclerosis. Therefore, elucidating the specific roles and mechanisms of the gut microbiota in modulating lipid metabolism in multiple sclerosis will accelerate the development of precision therapeutic strategies. In this review, we conduct an in-depth exploration of the interaction between the gut microbiota and lipid metabolism in the context of multiple sclerosis and provide a comprehensive summary of existing strategies targeting the gut microbiota and lipid metabolism for treating multiple sclerosis (including microbiota-based therapies, pharmacotherapy, and lifestyle modifications). Finally, we outline the present challenges in this field and offer an in-depth prospect for future directions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Multiple Sclerosis/metabolism/microbiology/therapy
*Lipid Metabolism
Animals

@article {pmid41243097,
year = {2025},
author = {Hang, WJ and Yin, R and Kang, XW and He, L and Cao, X and Chen, J},
title = {Berberine ameliorates high-fat diet-induced metabolic disorders through promoting gut Akkermansia and modulating bile acid metabolism.},
journal = {Chinese medicine},
volume = {20},
number = {1},
pages = {190},
pmid = {41243097},
issn = {1749-8546},
support = {82100402//National Natural Science Foundation of China/ ; 82370837//National Natural Science Foundation of China/ ; 2022CFB201//Bureau of Science and Technology of Hubei Province/ ; 2022YFE0209900//National Key Research and Development Program of China/ ; WZ21A02//Wuhan Municipal Health Commission's Scientific Research/ ; },
abstract = {BACKGROUND: Coptidis Rhizoma, the rhizome of Coptis chinensis Franch., has long been employed in the treatment of diabetes. Its active component, berberine, has been utilized in clinical practice; however, the underlying mechanisms of its protective effects remain to be fully elucidated.

METHODS: Metabolomics and lipidomics analyzed plasma metabolite and lipid changes in mice fed a high-fat diet and treated with 25 mg/kg/day berberine for three months. Metagenomics and microbiota transplantation identified gut microbiota responding to berberine. Co-administration of berberine and Akkermansia was studied for metabolic effects, analyzing plasma and fecal metabolomics.

RESULTS: Berberine reduced triglycerides and cholesterol, showing metabolic protective effects. Metagenomics identified Akkermansia as key to berberine's benefits, validated by microbiota transplantation. Berberine enhanced Akkermansia growth, preserving intestinal mucus and tight junctions. It promotes the conversion of cholesterol to bile acids by inhibiting adenosine 5 '-monophosphate -activated protein kinase (AMPK), which promotes the expression of cholesterol 7-alpha hydroxylase (CYP7A1). Co-administration of berberine and Akkermansia amplified these effects. Potential metabolites, including linoleic acid and N-acetylputrescine, contributed to the observed benefits.

CONCLUSION: Berberine, through Akkermansia, maintains intestinal integrity and reduces cholesterol, highlighting its potential as a therapeutic agent for metabolic disorders. Combining berberine with Akkermansia enhances its efficacy against hyperlipidemia.},
}

@article {pmid41242566,
year = {2025},
author = {Yousefi-Hashemabad, MJ and Hosseini Kakroudi, M and Pourashory, M and Forouzan, K and Yazdanpanah, N and Saleki, K and Rezaei, N},
title = {Intratumoral Bacterial Microbiota in Gastrointestinal Adenocarcinoma: From Computational Insights to Clinical Practice.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108174},
doi = {10.1016/j.micpath.2025.108174},
pmid = {41242566},
issn = {1096-1208},
abstract = {Intratumoral microbiota refers to bacteria and other organisms residing within the tumor microenvironment and are intriguingly found throughout the TME, including in cancer cells, immune cells, and stromal components. Among these microbiota, bacteria have gained attention due to their emerging roles in tumor biology. Recent research has uncovered new pathophysiological and therapeutic roles for targeting intratumoral bacterial microbiota. Emerging evidence pointed out that certain taxa, including Fusobacterium nucleatum and Porphyromonas gingivalis, can drive tumorigenic activity, whereas taxa such as Lactobacillus spp. may act as a protective agent. Overall, bacteria can influence cancer progression through mechanisms including immune modulation, metabolic reprogramming, and genomic instability. Furthermore, advances in artificial intelligence (AI) and microbiome profiling have identified prognostic microbial signatures and markers of treatment response. In addition, the mediation of the tumor microbiota via probiotics, antibiotics, engineered microbes, and fecal transplants exhibits novel approaches in targeted cancer therapy. The present review captures the role of intratumoral bacterial microbiota in adenocarcinomas and their significance in cancer development and progression as evidenced by experimental and clinical research.},
}

@article {pmid41241915,
year = {2025},
author = {Preetham, K and Chatterjee, J},
title = {Research trend on the emerging role of the microbiome in idiopathic male infertility.},
journal = {Antonie van Leeuwenhoek},
volume = {118},
number = {12},
pages = {193},
pmid = {41241915},
issn = {1572-9699},
mesh = {Male ; Humans ; *Infertility, Male/microbiology/etiology ; *Microbiota ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Oxidative Stress ; },
abstract = {Idiopathic male infertility remains a major challenge in reproductive medicine despite extensive diagnostic workups, prompting research into novel etiologies and interventions. Emerging evidence highlights the microbiome's role in modulating male reproductive health. This study analyzes global research trends on idiopathic male infertility and associated microbial health over the past two decades using a structured bibliometric approach. Data extracted from Scopus were examined through Biblioshiny and VOSviewer. The analysis reveals a clear transition from traditional genetic and oxidative stress-based studies to microbiome-centered and multi-omics investigations. Increased Research output and citation rates in recent years, underscoring the growing relevance of microbiome studies. Key contributors like Agarwal A, Wang X, Zhang H, and Lundy SD advanced understanding from genetic and oxidative causes to gut-testis and semen microbiome interactions. Leading contributors and countries, particularly China and the USA dominate collaborative networks. Key themes link microbial dysbiosis, oxidative stress, inflammation, and hormonal imbalance with impaired spermatogenesis. Environmental and lifestyle factors, including diet, alcohol, antibiotics, endocrine disruptors, and microplastics, were increasingly recognized as influencing microbiome-mediated fertility. Mechanistic insights into the gut-testis axis, endotoxemia, immune modulation, and nutrient metabolism suggest avenues for diagnostics and microbiome-based interventions, including probiotics, nutritional modulation, and fecal microbiota transplantation.},
}

Male
Humans
*Infertility, Male/microbiology/etiology
*Microbiota
Dysbiosis/microbiology
*Gastrointestinal Microbiome
Oxidative Stress

@article {pmid41241335,
year = {2025},
author = {Xu, Y and Ni, Y and Zhou, M and Gou, X},
title = {Qushi Huayu decoction alleviates NAFLD in mice by regulating gut microbiota homeostasis in the gut-liver axis via the pregnane X receptor.},
journal = {European journal of pharmacology},
volume = {1008},
number = {},
pages = {178366},
doi = {10.1016/j.ejphar.2025.178366},
pmid = {41241335},
issn = {1879-0712},
abstract = {BACKGROUND: Qushi Huayu decoction (QHD) is a traditional Chinese medicine formula with clinical experience in the treatment of non-alcoholic fatty liver disease (NAFLD). The gut-liver axis is directly connected via the portal vein, making gut microbiota dysbiosis and endotoxin circulation key drivers in the development and progression of NAFLD. However, the regulation of the gut-liver axis by QHD in NAFLD remains unreported, and its target mechanisms have yet to be elucidated.

MATERIALS AND METHODS: NAFLD was induced in male C57BL/6J mice via high-fat diet feeding, followed by 4 weeks of QHD administration. Comprehensive evaluation included serum biochemical analysis, liver histopathology examination, and quantification of proinflammatory enzyme activity. Mechanism studies were conducted via 16S rRNA sequencing, transcriptomics analysis, SCFAs analysis, RT-qPCR, Western blotting and ELISA techniques.

RESULTS: QHD therapy effectively ameliorates hepatic steatosis and lipid accumulation in a mouse model of NAFLD. In addition, QHD significantly increases intestinal tight junction proteins, thereby restoring intestinal barrier integrity and alleviating inflammatory responses. Transcriptomics revealed that QHD regulates multiple biological functions through multiple genes, in which inflammatory responses may play a key role. Simultaneously, QHD exerts beneficial modulation of the gut microbiota, increasing beneficial bacteria, particularly Akkermansia, while decreasing the prevalence of harmful microorganisms, such as Desulfovibrio. Fecal microbiota transplantation experiments demonstrates that gut microbiota remodeling partially mediates pharmacological efficacy of QHD against NAFLD. Notably, subsequent investigations identified that QHD altered the composition of the gut microbiota and the levels of acetic acid, propionic acid, and valeric acid in SCFAs in a PXR-dependent manner.

CONCLUSIONS: QHD exerts therapeutic effects on NAFLD by regulating the gut-liver axis. The mechanism by which QHD intervention ameliorates gut microbiota dysbiosis in NAFLD mice is associated with its regulation of PXR. This provides further scientific evidence and support for QHD's efficacy in improving NAFLD.},
}

@article {pmid41239321,
year = {2025},
author = {Alkuwaiti, SH and Skrabulyte-Barbulescu, J and Yassin, LK and Almazrouei, S and Aldhaheri, D and Alderei, M and BaniYas, S and Alshamsi, SH and Alnuaimi, A and Saeed, S and Alawadhi, M and Rutkowska-Gauvry, P and Ismail, FY and Hamad, MIK},
title = {Harnessing the microbiota-gut-brain axis to prevent and treat pediatric neurodevelopmental disorders: translational insights and strategies.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1286},
pmid = {41239321},
issn = {1479-5876},
abstract = {BACKGROUND: Pediatric neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), Rett syndrome (RTT), Tourette syndrome (TS), Down syndrome (DS), Fragile X syndrome (FXS), Prader–Willi syndrome (PWS), fetal alcohol spectrum disorder (FASD), pediatric epilepsy, congenital Zika syndrome (CZS), Wilson’s disease (WD), and cerebral palsy (CP), are associated with long-term impairments and high societal burden. Emerging evidence implicates the microbiota–gut–brain axis (MGBA) in early neurodevelopment with factors, such as maternal microbiota, birth mode, antibiotics, and infant diet shaping microbial colonization and influencing developmental outcomes.

OBJECTIVE: This review aims to synthesize current translational evidence from animal and human studies to address the following research questions: (1) How do disruptions in the MGBA contribute to the pathophysiology of pediatric neurodevelopmental disorders? (2) What microbiome alterations are consistently associated with these conditions? and (3) What ethical and safety considerations should be addressed in implementing early-life microbiome-based interventions? We also assess emerging microbiota-based interventions, including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and traditional therapies, and their potential to modulate disease outcomes.

CONCLUSION: The MGBA presents a promising, yet currently preliminary, target for early intervention in pediatric neurodevelopmental disorders. There is emerging evidence that therapies targeting the microbiota could have an effect on neurodevelopment and outcomes of health and disease; however, most of the findings are in the initial stages, and the evidence is still inconsistent. Therefore, the findings must be translated into mechanisms of action over extended periods with longitudinal multi-omic studies to identify possible intervention windows, optimize personalized therapies, and evaluate the safety and efficacy of interventions targeting the microbiome. Till that point, these microbiota-targeted approaches should be approached cautiously and treated as experimental in the realm of pediatric interventions, given the present-day state of evidence.},
}

@article {pmid41241180,
year = {2025},
author = {Han, H and Park, J and Zhang, R and Subramaniyam, N and Das, S and Ge, X and Babu Komakula, SS and Wang, C and Desert, R and Chen, W and Song, Z and Athavale, D and Anwar, A and Lantvit, D and Guzman, G and Frutos, MD and Ramos-Molina, B and Nieto, N},
title = {INTESTINAL EPITHELIAL CELL-DERIVED OSTEOPONTIN PROTECTS AGAINST METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS BY MODULATING BILE ACID COMPOSITION AND THE GUT MICROBIOME.},
journal = {Cellular and molecular gastroenterology and hepatology},
volume = {},
number = {},
pages = {101678},
doi = {10.1016/j.jcmgh.2025.101678},
pmid = {41241180},
issn = {2352-345X},
abstract = {BACKGROUND & AIMS: The gut-liver axis plays a critical role in metabolic dysfunction‒associated steatohepatitis (MASH). Osteopontin (OPN, encoded by SPP1) is implicated in chronic liver disease; however, its expression in intestinal epithelial cells (IECs) and role in MASH remain unclear.

METHODS: We evaluated intestinal OPN expression during MASH progression in patients. To determine the function of IEC-derived OPN, we generated Spp1 knock-in (Spp1[KI IEC]) and knock-out (Spp1[ΔIEC]) mice and fed them a high-fat, high-fructose, high-cholesterol diet to induce MASH.

RESULTS: IEC OPN expression decreased with MASH progression and was inversely associated with liver injury. Loss of Spp1 in IECs exacerbated MASH, whereas overexpression or oral OPN administration was protective. Spp1[ΔIEC] mice exhibited increased hepatic inflammation, disrupted IEC morphology, elevated IEC apoptosis, reduced epithelial cell turnover, and heightened intestinal permeability. They also showed hepatic 16s rRNA presence and elevated conjugated bile acids (BAs), particularly taurocholic acid (TCA) and taurodeoxycholic acid (TDCA), in portal serum. These BAs promoted hepatocyte injury and activated liver macrophages, enhancing inflammation both in vitro and in vivo. Fecal microbiome analysis revealed reduced abundance of bile salt hydrolase (BSH)-expressing bacteria. Fecal microbiota transplantation from Spp1[ΔIEC] mice or treatment with a BSH inhibitor further worsened MASH.

CONCLUSION: IEC-derived OPN protects against MASH by modulating BA composition and shaping the gut microbiome.},
}

@article {pmid41241177,
year = {2025},
author = {Rinaldi, M and Gatti, M and Giannella, M},
title = {Avoiding resistance development to newer drugs: open research lines.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.11.009},
pmid = {41241177},
issn = {1469-0691},
abstract = {BACKGROUND: The spread of multidrug-resistant Gram-negative bacteria (MDR-GNB), particularly those with carbapenem-resistant (CR) or difficult-to-treat resistance (DTR) phenotypes, is a major public health threat. New agents offer potent therapeutic options but carry the challenge of preserving their effectiveness against resistance.

OBJECTIVE: This narrative review summarizes antimicrobial and non-antimicrobial strategies to prevent or mitigate resistance development to novel agents.

SOURCES: We searched PubMed-MEDLINE for English-language articles published in the last five years.

CONTENT: Among antimicrobial strategies, we reviewed the role of optimizing pharmacokinetic/pharmacodynamic (PK/PD) targets for novel beta-lactam/beta-lactamase inhibitor combinations (BL/BLIc) and the impact of combination versus monotherapy regimens. Achieving aggressive joint PK/PD targets may help prevent resistance, supported by approaches such as continuous infusion of time-dependent agents and therapeutic drug monitoring. Current evidence does not demonstrate a routine benefit of combination therapy over monotherapy for novel drugs; however, available studies are limited in size and quality, and resistance emergence has rarely been a primary endpoint. Non-antimicrobial strategies reviewed include fecal microbiota transplantation (FMT), phage therapy, and active or passive immunization. These approaches may reduce the burden of MDR-GNB, particularly in high-risk populations such as immunocompromised patients, those undergoing invasive procedures, or patients with foreign bodies. By lowering pathogen load and transmission, these interventions could enhance the effectiveness of current drugs and limit further resistance development.

IMPLICATIONS: Prevention of resistance to novel BL/BLIc currently relies on optimized dosing and infusion strategies. The benefit of combination regimens remains uncertain and warrants further investigation, ideally with resistance emergence as a defined endpoint and addressed with appropriate analysis. Non-antimicrobial interventions show promise as adjunctive tools in high-risk settings and merit integration into broader resistance prevention frameworks.},
}

@article {pmid41240539,
year = {2025},
author = {Ma, J and Li, Y and Yang, Y and Zhao, L and Jiang, Y and Wong, TW and Zhang, D},
title = {Gut-liver axis mechanisms of Hippophae rhamnoides L. in non-alcoholic fatty liver disease prevention.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157517},
doi = {10.1016/j.phymed.2025.157517},
pmid = {41240539},
issn = {1618-095X},
abstract = {BACKGROUND: Phytosterol-rich Hippophae rhamnoides L. can ameliorate abnormal blood lipids in patients with non-alcoholic fatty liver disease (NAFLD). Its gut microbiota modulatory roles along gut-liver axis are not known.

OBJECTIVE: This study explored the preventive roles of H. rhamnoides L. against NAFLD and the associated gut-liver axis mechanisms.

METHODS: Sterols were extracted from H. rhamnoides L. seed oil (SHR) and subjected to LC-MS analysis. Their effects on body/liver/epididymal fat mass, intestinal microbiota, metabolites (DAO, D-LA, LPS) and SCFAs secretion, intestinal barrier (claudin-1, ZO-1) and liver lipid composition and molecular biology (AST, ALT, TC, TG, LDL-C, HDL-C, SREBP1c, SCD1, FAS, LXRα, PPARα) were examined in vivo against normal and high-fat diet mice. The modulatory action of microbiota on liver dysfunction was further verified through SHR-fed fecal transplantation into antibiotic-pretreated mice.

RESULTS: β-sitosterol, campesterol, stigmasterol, and ergosterol were the primary active constituents of SHR. With reference to high fat diet mice, SHR increased intestinal tight junction functionality, reducing inflammatory LPS migration to liver and hepatic lipid synthesis. SHR raised the relative abundance of Alloprevotella and Lachnospiraceae_NK4A136_group, and Bacteroides/Firmicutes ratio leading to increased SCFA secretion that strengthened intestinal barrier and reduced hepatic hyperlipidemia.

CONCLUSION: SHR effectively mitigated NAFLD by reducing hepatic lipid expression via regulating intestinal microbiota, its SCFA secretion and intestinal barrier.},
}

@article {pmid41239983,
year = {2025},
author = {Gabriel-Segard, T and Heberden, C and Mondot, S and Duquesnoy, M and Dicembre, M and Naudon, L and Philippe, C and Maximin, E and Blais, A and Jacota, M and Lapaque, N and Blottière, HM and Paul, S and Doré, J and Rabot, S and Hanachi, M},
title = {Anorexia nervosa symptoms are induced after specific gut microbiota dysbiosis transfer in germ-free mice.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2563701},
doi = {10.1080/19490976.2025.2563701},
pmid = {41239983},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Anorexia Nervosa/microbiology/therapy/physiopathology ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; Mice ; Mice, Inbred BALB C ; Female ; Disease Models, Animal ; Humans ; Germ-Free Life ; Feces/microbiology ; Adult ; Male ; },
abstract = {Anorexia nervosa (AN) is the most severe and life-threatening eating disorder. Its pathophysiology remains largely unknown, and no effective treatment currently exists for severe forms of the disease. Gut microbiota (GM) dysbiosis has been consistently reported in AN; however, no study has yet considered the role of the microbiota within the full spectrum of AN symptoms. To investigate the direct involvement of the microbiota in disease symptoms, we developed a murine model of fecal microbiota transplantation (FMT), using germ-free BALB/c mice colonized with fecal samples from well-characterized AN patients and healthy controls. Physiological, organ, and behavioral parameters were systematically monitored. We found that key AN-related features (including food restriction, anxiety-like behavior, physical hyperactivity, and elevated inflammatory responses) were transmitted to germ-free mice following transplantation with AN-derived microbiota. Likewise, organ-specific alterations associated with AN, such as liver dysfunction and disruption of ovarian follicles, were also reproduced. In conclusion, we demonstrate that the transfer of AN microbiota induces behavioral, physiological, and organ-level alterations reminiscent of the human disease. These findings highlight a major role of the gut microbiota in the symptomatology and progression of AN and open new therapeutic perspectives targeting this ecosystem.},
}

Animals
*Gastrointestinal Microbiome/physiology
*Anorexia Nervosa/microbiology/therapy/physiopathology
*Dysbiosis/microbiology
*Fecal Microbiota Transplantation
Mice
Mice, Inbred BALB C
Female
Disease Models, Animal
Humans
Germ-Free Life
Feces/microbiology
Adult
Male

@article {pmid41239968,
year = {2025},
author = {Kim, MS and Bisanz, JE},
title = {Design and application of synthetic human gut microbial communities.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2575923},
doi = {10.1080/19490976.2025.2575923},
pmid = {41239968},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Host Microbial Interactions ; Bacteria/genetics/classification ; Animals ; },
abstract = {The gut microbiome shapes host health through a complex network driven by both host‒microbe and microbe‒microbe interactions. Disruption of these interactions, often referred to as dysbiosis, is associated with a range of infectious and chronic diseases. Owing to the success of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridioides difficile infection, FMT has been explored as a therapeutic option for a range of microbiota-associated conditions, including inflammatory bowel disease and obesity. However, the microbial diversity that is the greatest strength of FMT is also its greatest liability. Concerns relating to reliance on human donors, potential for transmission of multidrug-resistant organisms or undesirable phenotypes demonstrate a need for alternate approaches, including the generation of synthetic alternatives to FMT, which can be built in the laboratory from individual strains. Furthermore, these communities are powerful tools for conducting mechanistic research allowing for the generation of 'knockout' communities, which are not possible when working with undefined fecal transplants. This review examines strategies for designing synthetic microbial communities that represent a new generation of microbiome-derived therapies. We highlight how synthetic microbial communities are being used to answer mechanistic questions about host-microbiome interactions relevant to health and disease. Finally, we examine the current clinical translation of these communities as live biotherapeutic products (LBPs). While the regulatory frameworks for LBPs continue to evolve, early clinical successes illuminate the potential for synthetic microbial communities to treat complex human diseases through targeted manipulation and restoration of the gut microbiome.},
}

Humans
*Gastrointestinal Microbiome
Fecal Microbiota Transplantation/methods
Dysbiosis/therapy/microbiology
Inflammatory Bowel Diseases/therapy/microbiology
Host Microbial Interactions
Bacteria/genetics/classification
Animals

@article {pmid41238277,
year = {2025},
author = {Pai, N and Sainath, NN},
title = {Diagnosis and Management of Small Intestinal Bacterial Overgrowth in Pediatric Short Bowel Syndrome.},
journal = {Gastroenterology clinics of North America},
volume = {54},
number = {4},
pages = {805-821},
doi = {10.1016/j.gtc.2025.07.005},
pmid = {41238277},
issn = {1558-1942},
mesh = {Humans ; *Short Bowel Syndrome/microbiology/complications/therapy ; *Intestine, Small/microbiology ; Child ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Breath Tests ; *Blind Loop Syndrome/diagnosis/therapy ; },
abstract = {This article explores the diagnosis and management of small intestinal bacterial overgrowth in children with short bowel syndrome, a population affected by altered anatomy, dysmotility, and medication-related risk factors. Diagnostic accuracy is limited by the feasibility, and specificity of breath testing and small bowel aspirates. While antibiotics are commonly used, concerns about recurrence and antibiotic resistance remain significant. Emerging nutritional strategies and precision-based, microbiome-targeted therapies offer promising adjunctive treatment options.},
}

Humans
*Short Bowel Syndrome/microbiology/complications/therapy
*Intestine, Small/microbiology
Child
Anti-Bacterial Agents/therapeutic use
Gastrointestinal Microbiome
Breath Tests
*Blind Loop Syndrome/diagnosis/therapy

@article {pmid41238092,
year = {2025},
author = {Ye, M and Ju, H and Ren, G and Hu, J},
title = {The Role of Microbiome in Immunotherapy: Insights and Perspectives.},
journal = {Seminars in cancer biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.semcancer.2025.11.001},
pmid = {41238092},
issn = {1096-3650},
abstract = {The intricate interplay between the gut microbiome and the host immune system has been recognized as a pivotal determinant of clinical outcomes in cancer immunotherapy. Mounting evidence suggests that specific microbial communities are associated with both the efficacy and toxicity of immune checkpoint inhibitors in diverse malignancies, underscoring the microbiome's role in modulating systemic and tumour-localized immunity. Mechanistically, the microbiome shapes antitumour immunity by affecting antigen presentation, activation of effector cells, immunosuppression and adverse effects. Key microbial components and metabolites present in distinct anatomical niches have been identified as promoters or inhibitors of therapeutic responsiveness via multiple pathways. Harnessing this knowledge, microbiome-targeted strategies such as antibiotic, probiotic, fecal microbiota transplantation, and dietary modulation are regarded as potential adjuvant therapies to enhance the efficacy of anti-tumour therapies. Although significant progress has been achieved in preclinical studies, challenges persist in translating these findings into standardized clinical applications.},
}

@article {pmid41237834,
year = {2025},
author = {Yang, J and Li, J},
title = {Nanotechnology-Microbiota Synergy in Cancer Immunotherapy.},
journal = {Critical reviews in oncology/hematology},
volume = {},
number = {},
pages = {105018},
doi = {10.1016/j.critrevonc.2025.105018},
pmid = {41237834},
issn = {1879-0461},
abstract = {The global burden of cancer continues to escalate, yet the efficacy of current targeted therapies and immune checkpoint inhibitors (ICIs) is often hampered by drug resistance and immune escape. The gut microbiota orchestrates tumor progression and ICI efficacy bidirectionally via the "microbiota-immune-tumor" axis. However, traditional interventions, including fecal microbiota transplantation and antibiotics, are limited by inherent drawbacks such as poor targeting. Nanotechnology can overcome this limitation: it not only enables precise targeting of the gut microbiota and reshapes the tumor immune microenvironment to synergistically enhance ICI efficacy but also reverses drug resistance in tumor chemotherapy, radiotherapy, and targeted therapy through multiple strategies. Additionally, it can synergize with probiotics, extracellular vesicles, and other agents to achieve tumor therapy. This review synthesizes current understanding of gut microbiota-immune crosstalk, the microbiota's role in regulating ICI efficacy, and the central applications of nanotechnology, thereby proposing novel synergistic strategies for cancer treatment.},
}

@article {pmid41237775,
year = {2025},
author = {Van Hul, M and Cani, PD},
title = {From microbiome to metabolism: Bridging a two-decade translational gap.},
journal = {Cell metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmet.2025.10.011},
pmid = {41237775},
issn = {1932-7420},
abstract = {The mapping of the human genome sparked high expectations for biomedical breakthroughs, yet attention has since shifted toward the human microbiome as a key player in health and disease. Pioneering studies revealed striking inter-individual variability and numerous associations between gut microbiota and a wide range of conditions (i.e., obesity, diabetes, cardiovascular and inflammatory bowel diseases, autism, allergies, neurodegenerative diseases, and cancers). However, the field has faced a deluge of correlative "dysbiosis" studies with limited causal evidence. Although animal models have provided crucial mechanistic insights, translating these findings to humans has proven challenging. Interventions such as fecal microbiota transplantation, prebiotics, probiotics, and postbiotics often yield inconsistent or modest effects in clinical trials. This gap highlights the need for precision, functional profiling, and integration of multi-omics , for instance, through artificial intelligence. In this perspective, we discuss what microbiome research offers as a transformative shift and how we conceptualize disease, favoring systems biology and personalized interventions over reductionist approaches.},
}

@article {pmid41236646,
year = {2025},
author = {Ochi, T and Takeda, M and Asahara, T and Kurita, A and Ogata, Y and Suzuki, M and Takei, H and Nittono, H and Miyano, G and Koga, H and Lane, GJ and Okazaki, T and Saiura, A and Mizuta, K and Kasahara, M and Yamataka, A and Yamashiro, Y},
title = {Postoperative gut dysbiosis in biliary atresia patients treated by portoenterostomy or liver transplantation.},
journal = {Pediatric surgery international},
volume = {42},
number = {1},
pages = {9},
pmid = {41236646},
issn = {1437-9813},
support = {22K11861//Japan Society for the Promotion of Science KAKENHI grant/ ; },
mesh = {Humans ; *Biliary Atresia/surgery ; *Dysbiosis/microbiology/etiology ; *Liver Transplantation/adverse effects ; Male ; Female ; *Portoenterostomy, Hepatic/adverse effects ; *Gastrointestinal Microbiome ; *Postoperative Complications/microbiology ; Infant ; Feces/microbiology/chemistry ; Bile Acids and Salts/analysis ; Case-Control Studies ; },
abstract = {PURPOSE: To assess how surgery and management protocols affect gut microbiota in postoperative biliary atresia (BA) patients by comparing survivors with native livers (NL) or transplanted livers (TL) with healthy non-surgical controls (CL).

METHODS: Subjects were 62 post-portoenterostomy BA patients divided into 2 groups (NL and TL) and CL. All subjects were clinically stable with no dietary restrictions throughout the study period. Stool samples were compared for gut microbiota, organic acids, and fecal bile acids, while blood samples were compared for serum biochemistry and serum bile acids.

RESULTS: Stool samples from CL (n = 30) were normal while NL (n = 31) and TL (n = 31) showed gut dysbiosis with significantly decreased total bacteria and reduced predominance of obligate anaerobes, and an abundance of Clostridioides difficile, Enterobacteriaceae, and Enterococcus. The latter two were more abundant in TL than NL. Biochemistry was normal in TL. In NL, elevated AST/ALT correlated with increased Clostridioides difficile, decreased Bacteroides fragilis group, and decreased Lactobacilli. Fecal secondary bile acids were lower and serum primary and secondary bile acids were higher in NL and TL compared with CL.

CONCLUSION: Gut dysbiosis was present in both NL and TL. Pathogenic florae were more abundant in TL despite TL biochemistry being normal.},
}

Humans
*Biliary Atresia/surgery
*Dysbiosis/microbiology/etiology
*Liver Transplantation/adverse effects
Male
Female
*Portoenterostomy, Hepatic/adverse effects
*Gastrointestinal Microbiome
*Postoperative Complications/microbiology
Infant
Feces/microbiology/chemistry
Bile Acids and Salts/analysis
Case-Control Studies

@article {pmid41235136,
year = {2025},
author = {Wu, Y and Pan, S and Yin, C and Kong, Y and Huo, W and Wang, Q and Wu, J and Li, L and Wei, J and Lu, C and Han, L and Lu, Y},
title = {PSORI-CM02 Restores Epidermal Differentiation in Psoriasis via the Gut Microbiota-Sphingolipid Axis.},
journal = {Drug design, development and therapy},
volume = {19},
number = {},
pages = {9993-10010},
pmid = {41235136},
issn = {1177-8881},
mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Psoriasis/drug therapy/metabolism/pathology ; Mice ; Humans ; *Cell Differentiation/drug effects ; *Sphingolipids/metabolism ; *Epidermis/drug effects/pathology/metabolism ; Keratinocytes/drug effects/metabolism ; },
abstract = {BACKGROUND: Psoriasis is linked to gut dysbiosis and disturbed sphingolipid metabolism. PSORI-CM02 improves epidermal differentiation, yet its impact on the microbiota-sphingolipid axis remains unknown.

METHODS: Transcriptomics of patient keratinocytes, Carmofur inhibition in IMQ mice, and multi-omics (metabolomics, metagenomics) of skin, lymph nodes and gut were combined. SPF, PGF and GF mice underwent FMT to test microbiota dependency.

RESULTS: Psoriatic lesions showed sphingolipid pathway enrichment. Carmofur enhanced differentiation. PSORI-CM02 lowered PASI, spleen index, and tissue levels of ceramide, S1P, C1P and sphingomyelin while restoring Flg, Krt10 and Krt14. It reduced Turicibacter, Bacteroides, Bifidobacterium and Acetobacter. PSORI-CM02-derived microbiota reproduced therapeutic effects in all FMT settings.

CONCLUSION: PSORI-CM02 reshapes gut microbiota, normalizes sphingolipid metabolism and improves epidermal differentiation to treat psoriasis.},
}

*Gastrointestinal Microbiome/drug effects
Animals
*Psoriasis/drug therapy/metabolism/pathology
Mice
Humans
*Cell Differentiation/drug effects
*Sphingolipids/metabolism
*Epidermis/drug effects/pathology/metabolism
Keratinocytes/drug effects/metabolism

@article {pmid41234596,
year = {2025},
author = {Du, Y and Li, Y and Yu, M and Yu, Y and Zhang, Y and Wang, X and He, J and Lin, L and Shen, B and Gong, Y and Zhu, J and Zou, B and Liu, Y and Huang, M and Lu, Y},
title = {Fecal microbiota transplantation plus immune checkpoint inhibitor rechallenges in patients with advanced non-small cell lung cancer: a single-arm exploratory study.},
journal = {Translational lung cancer research},
volume = {14},
number = {10},
pages = {4541-4559},
pmid = {41234596},
issn = {2218-6751},
abstract = {BACKGROUND: The management of advanced non-small cell lung cancer (NSCLC) after progression on initial immunotherapy represents a significant clinical challenge. Immune checkpoint inhibitor (ICI) rechallenge is a considered option, yet its efficacy remains limited. Strategies to enhance the efficacy of ICI rechallenge are urgently needed. There is a pressing need for novel strategies to sensitize tumors to ICI rechallenge. Previous studies have established a correlation between the gut microbiota and the tumor response to immunotherapy, and have explored the application of fecal microbiota transplantation (FMT) in modifying the immune response by restoring the gut microbiota. However, the potential of FMT from healthy donor to reverse immunotherapy resistance in patients with NSCLC has not been previously investigated. This preliminary study aimed to provide initial insights into the safety, tolerability, and potential efficacy of the combined therapy of FMT from healthy donor with immunotherapy rechallenge in NSCLC patients.

METHODS: In this single-arm exploratory study, patients with advanced NSCLC who progressed after prior immunotherapy were screened and enrolled based on predefined eligibility criteria, including prior response to ICIs and adequate organ function. Eligible patients received oral FMT capsules from healthy donors followed by rechallenge with camrelizumab. The primary endpoint was safety and feasibility [incidence of adverse events (AEs) graded by CTCAE v5.0]. Secondary end points included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Fecal and blood samples were collected for exploratory analyses of microbiota, metabolome, and T cell receptor (TCR) repertoire.

RESULTS: Seven patients (all male, median age 55 years) were enrolled and constituted the analysis population. The majority (5/7) had received three or more prior lines of therapy. During the follow-up period, none experienced grade 4 or higher AEs. The treatment-related AEs were mainly associated with immunotherapy, and only grade 1 FMT-related AEs (e.g., nausea, diarrhea, bloating, and constipation) were reported. One patient achieved a partial response (PR) and one achieved stable disease (SD) with PFS times of 14.6 and 8.1 months, respectively. The median PFS was 1.5 months [95% confidence interval (CI): 1.24-1.75], and the OS was 12.1 months (95% CI: 0.3-23.9) for all patients. Moreover, the treatment modulated the composition of the intestinal flora in all patients, with alpha diversity increasing in responders and decreasing in non-responders.

CONCLUSIONS: The results indicated that the combined therapy of FMT and immunotherapy rechallenge was feasible and demonstrated a tolerable safety profile in this small cohort. The observed clinical activity is preliminary. These findings support the need for larger, controlled trials to assess the efficacy of this approach.},
}

@article {pmid41234231,
year = {2025},
author = {Huang, L and Wang, S and Zhang, H and Feng, S and Zhong, H and Chen, J and Xie, W and Wu, L and Zhang, T and He, X and Yang, J},
title = {Clinical efficacy evaluation of washed microbiota transplantation treatment for metabolic related fatty liver disease and its impact on tongue coating microorganisms.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1684173},
pmid = {41234231},
issn = {1664-2392},
mesh = {Humans ; Animals ; *Tongue/microbiology ; Mice ; Male ; Female ; Middle Aged ; *Microbiota ; *Fecal Microbiota Transplantation/methods ; Adult ; Mice, Inbred C57BL ; Treatment Outcome ; RNA, Ribosomal, 16S/genetics ; *Non-alcoholic Fatty Liver Disease/therapy/microbiology ; },
abstract = {OBJECTIVE: The present study aims to explore the impact of washed microbiota transplantation (WMT) on the tongue microbiota composition of individuals with metabolic-associated fatty liver disease (MAFLD) and elucidate its biological correlations.

METHODS: We conducted a comprehensive analysis of hepatic fat deposition and characterized the tongue coating microbiota using 16S rRNA gene sequencing in MAFLD patients before and after undergoing WMT treatment. Furthermore, a MAFLD mouse model was established for additional validation.

RESULTS: At the genus level, significant differences in tongue coating microbiota structure were observed between MAFLD patients and HC. Specifically, Neisseria positively correlated with the BARD score, Porphyromonas and Rhodococcus positively correlated with fat decay, and Petostreptococcus, a conditionally pathogenic bacterium, exhibited a significantly higher relative abundance in MAFLD patients compared to HC. Conversely, Actinomyces positively correlated with the FIB-4 score, Megasphaera negatively correlated with the APRI score, and Subdoligulum negatively correlated with low-density lipoprotein levels. Notably, following effective WMT treatment, patients exhibited improved symptoms, with a significant reduction in the relative abundance of Petostreptococcus and an increase in potential probiotics such as Lachnospiraceae and Bifidobacterium in their tongue coating microbiota. Additionally, structural differences in the tongue coating microbiota were identified at the genus level between MAFLD model mice and HC mice. After WMT treatment, the relative abundance of conditionally pathogenic bacteria like Enterococcus was significantly decreased in MAFLD model mice.

CONCLUSIONS: WMT not only significantly ameliorates liver fat deposition in MAFLD patients but also alters the tongue coating microbial structure associated with disease severity, thereby potentially mitigating adverse patient outcomes.},
}

Humans
Animals
*Tongue/microbiology
Mice
Male
Female
Middle Aged
*Microbiota
*Fecal Microbiota Transplantation/methods
Adult
Mice, Inbred C57BL
Treatment Outcome
RNA, Ribosomal, 16S/genetics
*Non-alcoholic Fatty Liver Disease/therapy/microbiology

@article {pmid41232540,
year = {2025},
author = {Wieringa, JW and Binyamin, D and Jankelowitz, IA and Schweitzer, R and Turjeman, S and Khatib, S and Esser, MJ and van der Woude, CJ and Fuhler, GM and Koren, O},
title = {Intestinal barrier alterations in mice following fecal microbiota transplant from children of IBD-affected mothers.},
journal = {Med (New York, N.Y.)},
volume = {},
number = {},
pages = {100915},
doi = {10.1016/j.medj.2025.100915},
pmid = {41232540},
issn = {2666-6340},
abstract = {BACKGROUND: Inflammatory bowel disease (IBD) carries a hereditary risk, which is higher through maternal, rather than paternal, inheritance. Like their mothers, children born to mothers with IBD have an altered microbiome shortly after birth.

METHODS: To investigate whether this altered microbiome persists later in life and affects the intestinal mucosa, the fecal microbiome was analyzed in samples from 44 infants ranging from 0 to 10 years of age born to 26 women with IBD. Forty-four age-matched children of 29 women without IBD served as controls. Fecal microbiota transplantation (FMT) to germ-free mice was carried out from 4-year-olds born to mothers with IBD and controls. Markers of inflammation, barrier function, and metabolic changes were investigated.

FINDINGS: Intestinal microbiomes were more similar between women with IBD and their children than between control mothers and their offspring. Microbial changes were noticeable in children from mothers with IBD from the age of 4 years compared to children of controls. No inflammatory response was present in the mucosa of mice receiving FMT from children of mothers with IBD; however, mesenteric lymph node enlargement and decreased expression of barrier genes Zo1 and Ocln were seen in mice receiving FMT from these children compared to controls. Additionally, reduced colonic expression of the immunological tolerance enzyme Ido1 coincided with decreased serum kynurenine/tryptophan ratios.

CONCLUSIONS: Fecal microbiomes of children of mothers with IBD exhibit characteristics that reduce epithelial tight junction barrier genes and tolerogenic tryptophan metabolism. Microbiome-induced gut barrier disruptions may contribute to an enhanced IBD predisposition in infants of mothers with IBD.

FUNDING: This work was funded by ZonMw.},
}

@article {pmid41161092,
year = {2025},
author = {Gu, M and Peng, X and Dai, X and Ma, X and Ge, W and Yang, S and Wei, W},
title = {Tannic acid decreased the synthesis and secretion of sIgA in the small intestine of Brandt's voles (Lasiopodomys brandtii) by modifying gut microbiota.},
journal = {Biochemical and biophysical research communications},
volume = {789},
number = {},
pages = {152846},
doi = {10.1016/j.bbrc.2025.152846},
pmid = {41161092},
issn = {1090-2104},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arvicolinae/microbiology/immunology ; *Intestine, Small/drug effects/microbiology/metabolism/immunology ; *Tannins/pharmacology ; *Immunoglobulin A, Secretory/metabolism/biosynthesis ; Male ; Fecal Microbiota Transplantation ; Polyphenols ; },
abstract = {Tannic acid (TA), a representative plant secondary metabolite, impairs intestinal immune function and alters intestinal microbiota abundance of Brandt's voles. Whether TA reduces intestinal immune function by modifying the gut microbiota remains unknown. In this study, Brandt's voles were divided into three groups for microbiota transplantation (FMT): normal saline (Ab), microbiota from normal saline administration (R-Con), and microbiota from TA administration (R-TA). Then, the intestinal morphology, immune indices, gut flora, and microbiota metabolites were measured after FMT. The findings showed that the sIgA content of small intestine of voles in the R-TA group were lower than in the R-con group. Additionally, the voles in the R-con group exhibited higher mRNA levels of PIgR, J-chain, BAFF, and APRIL than in the R-TA group. The ANOSIM results showed significant structural differentiation, reflecting that the β-diversity of the cecal microbiome was altered. Moreover, the voles in the R-con group had a higher concentration of butyric acid in the cecum compared to both the Ab and R-TA groups. In the experiment 2, the sIgA content in the duodenum and ileum of Brandt's voles in the TBA group (1200 mg•kg[-1]d[-1] TA + butyrate) was significantly higher than that in the TNS group (1200 mg•kg[-1]d[-1] TA + normal saline). To summarize, the "TA microbiota" decreased the slgA secretion and synthesis in the small intestine by reducing butyric acid content, thus lowering the intestinal immune capacity of Brandt's voles. The findings provide the experimental basis to prove the critical role of gut microorganisms in controlling animal physiological processes.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Arvicolinae/microbiology/immunology
*Intestine, Small/drug effects/microbiology/metabolism/immunology
*Tannins/pharmacology
*Immunoglobulin A, Secretory/metabolism/biosynthesis
Male
Fecal Microbiota Transplantation
Polyphenols

@article {pmid41232361,
year = {2025},
author = {Bishoyi, AK and Al-Hasnaawei, S and Salem, KH and Ganesan, S and Shankhyan, A and Nanda, A and Sinha, A and Ray, S and Nathiya, D and Hammady, FJ},
title = {Gut microbiome metabolites in lung cancer: The emerging importance of short-chain fatty acids.},
journal = {International immunopharmacology},
volume = {168},
number = {Pt 1},
pages = {115821},
doi = {10.1016/j.intimp.2025.115821},
pmid = {41232361},
issn = {1878-1705},
abstract = {Short-chain fatty acids (SCFAs), which are produced from the fermentation by the gut microbiota of dietary fiber, are now proven to play a vital role in the growth control of lung cancer and drug response. SCFAs have mechanisms of action, including the inhibition of histone deacetylases, activation of G-protein-coupled receptors, and metabolic reprogramming. SCFAs suppress tumor growth, induce apoptosis, suppress angiogenesis, and modulate epithelial-mesenchymal transition. Besides the above direct antitumor effects, SCFAs enhance the therapeutic effect of immune checkpoint inhibitors and reduce the toxicity of radiotherapy and chemotherapy by maintaining the mucosal barrier and restoring systemic immune homeostasis. Butyrate function is highly dualistic; it is usually protective but may confer multidrug resistance under certain therapeuticconditions. To reconcile these opposing effects is akey challenge in the translation of microbiota-based therapeutics and interventions. Therapies such as probiotics, fecal microbiota transplantation, and designed microbial consortia all target SCFAs as central mediators of microbiome-host communication. Overall, SCFAs are candidate metabolic co-adjuvants that can maximize therapeutic efficacy, suppress unacceptable side effects, and redirect therapeutic approaches to lung cancer.},
}

@article {pmid41229982,
year = {2025},
author = {Chen, Z and Li, L and Jin, D and Zhao, Y and Malard, F and Huang, H and Ye, Y and Mohty, M},
title = {Gut microbiota and acute graft-versus-host disease.},
journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu},
volume = {37},
number = {5},
pages = {657-666},
pmid = {41229982},
issn = {1000-9604},
abstract = {Acute graft-versus-host disease (aGVHD) is an important complication which critically impacts the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation. Increasing evidence suggests that dysbiosis of the gut microbiota plays a key role in aGVHD pathogenesis. The biological process involves compromised intestinal barrier integrity, amplified inflammation driven by the translocation of microbial products like lipopolysaccharide, and finally the dysregulated immune response centralized by T cell activation and differentiation. Meanwhile, certain microbial metabolites such as short-chain fatty acids and secondary bile acids exert protective effects. The clinical relevance of these findings is underscored by studies establishing that specific gut microbial signatures, such as low diversity and single pathogen dominance, independently predict aGVHD morbidity and mortality. From a therapeutic perspective, the microbiome has emerged as an important therapeutic target for aGVHD. Fecal microbiota transplantation has shown significant efficacy in clinical trials for prophylaxis and treatment of aGVHD, providing definitive proof-of-concept for ecological restoration. This review synthesizes these foundational mechanistic insights, from metabolic disruption to host-microbe crosstalk at the mucosal barrier, and details the rapidly advancing clinical landscape of microbiome-targeted diagnostics and therapeutics for aGVHD.},
}

@article {pmid41229686,
year = {2025},
author = {Tian, R and Chong, CJ and Bai, YY and Chen, N and Qiao, RR and Wang, K and Wang, YW and Zhao, P and Zhao, CB and Tang, YP and Zhang, L and Zhang, Q},
title = {The role of gut microbiota in diarrhea and its alleviation through microbiota-targeted interventions.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1630823},
pmid = {41229686},
issn = {1664-302X},
abstract = {Diarrhea is a common gastrointestinal disease and closely related to the balance of the gut microbiota (GM). In turn, dysregulation of the GM can affect the onset and progression of diarrhea through regulating the metabolism, intestinal immune function, intestinal barrier function and changes in the brain-gut axis of host. Although increasing evidence suggests that GM is associated with gastrointestinal homeostasis and disease, the underlying mechanisms are not fully understood. GM disorder was often accompanied by diarrhea patients and animals, and the diarrhea caused by GM imbalance mainly involved the effects on short chain fatty acids (SCFAs), bile acids (BAs), intestinal barrier, immune system, and brain-gut microbiota axis (BGMA). In addition, intervening in the GM (probiotics, fecal microbiota transplantation and bacteriophage therapy) has been shown to be an effective way to alleviate diarrhea. In this review, the mechanism of diarrhea occurrence, probiotics, fecal microbiota transplantation and bacteriophage therapy intervene in diarrhea by regulating GM from basic and clinical research were summarized and discussed. We aim to provide the latest reference for studying the mechanism of treating diarrhea from the perspective of GM, and provide data support for clinical treatment of diarrhea.},
}

@article {pmid41229548,
year = {2025},
author = {Xiao, Y and Wei, L and Yu, J and Liu, Y},
title = {Fecal Microbiota Transplantation for Attention-Deficit/Hyperactivity Disorder: Mechanisms, Evidence, and Future Directions.},
journal = {International journal of general medicine},
volume = {18},
number = {},
pages = {6757-6767},
pmid = {41229548},
issn = {1178-7074},
abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. While pharmacological and behavioral therapies remain first-line treatments, their limitations in efficacy, tolerability, and long-term adherence underscore the need for innovative interventions. Growing evidence highlights the role of the microbiota-gut-brain axis (MGBA) in ADHD pathophysiology, particularly involving immune dysregulation, neurotransmitter imbalance, metabolic disruption, and epigenetic alterations. Fecal microbiota transplantation (FMT), as a microbiota-based intervention, has shown promise in restoring MGBA homeostasis and modulating neural function through multiple mechanisms. This review summarizes current preclinical and clinical research on FMT in ADHD, covering its effects on neuroinflammation, neurotransmitter pathways, vagus nerve and HPA axis signaling, and epigenetic reprogramming. Although preclinical models and early human data indicate potential behavioral benefits and mechanistic plausibility, methodological heterogeneity, limited sample sizes, and incomplete mechanistic validation pose significant challenges. Future research should prioritize protocol standardization, randomized controlled trials, biomarker discovery, and ethical regulation to facilitate the safe and effective clinical translation of FMT in ADHD treatment.},
}

@article {pmid41228422,
year = {2025},
author = {Diotaiuti, P and Misiti, F and Marotta, G and Falese, L and Calabrò, GE and Mancone, S},
title = {The Gut Microbiome and Its Impact on Mood and Decision-Making: A Mechanistic and Therapeutic Review.},
journal = {Nutrients},
volume = {17},
number = {21},
pages = {},
doi = {10.3390/nu17213350},
pmid = {41228422},
issn = {2072-6643},
support = {MUR Decree n. 105123.06.2022 PNRR Missione 4 Componente 2 Investimento 1.5-CUP H33C22000420001//Project ECS0000024 "Ecosistema dell'innovazione-Rome Technopole" financed by EU NextGeneration EU plan/ ; },
mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Affect/physiology ; *Decision Making/physiology ; Animals ; Cognition ; Probiotics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; },
abstract = {Background/Objectives: The gut microbiome is increasingly recognized as a key modulator of central nervous system function through the gut-brain axis. Dysbiosis has been associated with neuropsychiatric disorders such as depression, anxiety, impulsivity, cognitive decline, and addiction. This review aims to synthesize mechanistic insights and therapeutic perspectives on how gut microbiota influence mood regulation, decision-making, and cognitive processes. Methods: A comprehensive narrative review was conducted using peer-reviewed articles retrieved from PubMed, Scopus, and Web of Science up to August 2025. Studies were included if they explored microbiota-related effects on behavior, mood, cognition, or decision-making using human or animal models. Emphasis was placed on molecular mechanisms, microbiome-targeted therapies, and multi-omics approaches. Results: Evidence indicates that gut microbiota modulate neurochemical pathways involving serotonin, dopamine, GABA, and glutamate, as well as immune and endocrine axes. Microbial imbalance contributes to low-grade systemic inflammation, impaired neuroplasticity, and altered stress responses, all of which are linked to mood and cognitive disturbances. Specific microbial taxa, dietary patterns, and interventions such as probiotics, prebiotics, psychobiotics, and fecal microbiota transplantation (FMT) have shown promise in modulating these outcomes. The review highlights methodological advances including germ-free models, metagenomic profiling, and neuroimaging studies that clarify causal pathways. Conclusions: Gut microbiota play a foundational role in shaping emotional and cognitive functions through complex neuroimmune and neuroendocrine mechanisms. Microbiome-based interventions represent a promising frontier in neuropsychiatric care, although further translational research is needed to define optimal therapeutic strategies and address individual variability.},
}

*Gastrointestinal Microbiome/physiology
Humans
*Affect/physiology
*Decision Making/physiology
Animals
Cognition
Probiotics
Dysbiosis/microbiology
Fecal Microbiota Transplantation
Prebiotics/administration & dosage

@article {pmid41226824,
year = {2025},
author = {de Groen, P and Blok, LCHM and Fuhri Snethlage, CM and Hanssen, NMJ and Rampanelli, E and Nieuwdorp, M},
title = {Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
doi = {10.3390/ijms262110788},
pmid = {41226824},
issn = {1422-0067},
support = {09150182010020//Personal NWO-VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; 4-SRA-2025-1766-M-B//BREAKTHROUGH T1D Grant/ ; 09150172210050//ZonMw-VIDI grant 2023/ ; 2021T055//Senior Clinical Dekker grant by the Dutch Heart Foundation/ ; 09150172210019//ZONMW-VIDI grant 2023/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; *Metabolomics/methods ; *Immunomodulation ; Animals ; Fecal Microbiota Transplantation ; Autoimmunity ; },
abstract = {Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T-cell-mediated destruction of pancreatic beta cells, resulting in insulin deficiency. Both genetic predisposition and environmental factors contribute to T1D development, with growing evidence implicating the gut microbiome as a critical environmental modulator in disease pathogenesis. Gut microbial composition and derived metabolites influence immune homeostasis and autoimmunity. This review summarizes recent advances elucidating immune dysregulations in T1D and novel therapeutic strategies to preserve beta cell function. We discuss approaches such as immune cell engineering, including CAR-Treg therapy, and targeted modulation of immune signaling pathways like JAK-STAT. Furthermore, we explore the role of the gut microbiota and its metabolites in modulating host immunity and describe emerging microbiome-targeting interventions, including fecal microbiota transplantation and metabolite supplementation. These interventions show promise in modulating disease progression in preclinical and early clinical studies. An integrated understanding of immune and microbiome-related mechanisms is critical for developing next-generation therapies. Further research and clinical trials are needed to optimize these approaches and translate them into durable, personalized treatments for individuals with T1D.},
}

Humans
*Diabetes Mellitus, Type 1/therapy/immunology/metabolism/microbiology
*Gastrointestinal Microbiome/immunology
*Metabolomics/methods
*Immunomodulation
Animals
Fecal Microbiota Transplantation
Autoimmunity

@article {pmid41223655,
year = {2025},
author = {Chen, J and Gu, M and Zhang, M and Wang, S and Zhang, X and Zhu, Z and Gan, Q},
title = {Stage-specific gut microbial restructuring drives estrous transition in rabbits.},
journal = {Animal bioscience},
volume = {},
number = {},
pages = {},
doi = {10.5713/ab.250529},
pmid = {41223655},
issn = {2765-0189},
abstract = {OBJECTIVE: This study aimed to investigate the relationship between colonic microbiota and estrous cycle transition in rabbits by integrating 16S rRNA gene sequencing and metabolomic analyses, and to identify key microbial taxa and metabolites involved in estrus regulation.

METHODS: Female New Zealand white rabbits were divided into diestrus and early estrus groups based on vulvar mucosa color and serum estradiol (E2) concentration. Colonic microbiota dynamics were assessed via 16S rRNA sequencing, while metabolomes of colonic contents were profiled using UHPLC-MS/MS. Fecal microbiota transplantation (FMT) was performed by orally administration of colonic contents from diestrus or early estrus rabbits to mice with disrupted estrous cycles, to evaluate the regulatory effects of microbiota. Exogenous indole-3-acetic acid (IAA) was administered to both mice and rabbits to assess its role in estrus onset and cyclicity restoration.

RESULTS: Colonic microbial composition differed significantly between diestrus and early estrus rabbits. The genera Anaerostipes and Ruminiclostridium were enriched in early estrus, while the genera Oscillospirales UCG_010 and UCG_005 were more abundant in diestrus. FMT from early estrus donors restored cyclicity in mice with disrupted cycles, whereas diestrus FMT did not. Metabolomics identified IAA as a key elevated metabolite in early estrus, and this metabolite accelerated estrus onset and restored cyclicity in both mice and rabbits.

CONCLUSION: These findings demonstrate that gut microbiota restructuring regulates the estrous transition of rabbits, providing a basis for developing microbiota-targeted strategies to enhance reproductive efficiency in rabbit production and optimize animal reproductive management.},
}

@article {pmid40751372,
year = {2025},
author = {Bryant, JA and Straub, TJ and Pardi, DS and Litcofsky, KD and Kelly, CR and Chafee, ME and Cohen, SH and Khanna, S and Berenson, CS and Wortman, J and Sims, M and Ford, CB and Lombardo, MJ and McGovern, BH and von Moltke, L and Kraft, CS and Henn, MR and Hasson, BR},
title = {Comparability of Gastrointestinal Microbiome and Bile Acid Profiles in Patients With First or Multiply Recurrent Clostridioides difficile Infection.},
journal = {The Journal of infectious diseases},
volume = {232},
number = {5},
pages = {e733-e740},
doi = {10.1093/infdis/jiaf408},
pmid = {40751372},
issn = {1537-6613},
support = {//Seres Therapeutics/ ; },
mesh = {Humans ; *Bile Acids and Salts/analysis/metabolism ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/drug therapy/therapy ; Male ; Female ; Feces/microbiology/chemistry ; Middle Aged ; *Clostridioides difficile ; Aged ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; Adult ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) treatment guidelines suggest varied approaches for patients with first (frCDI) or multiply recurrent CDI (mrCDI). Low microbial diversity, elevated primary bile acids (BA), and low secondary BA concentrations favor germination of C. difficile spores into toxin-producing bacteria and are believed to increase rCDI risk. Greater understanding of the gastrointestinal (GI) microbiome in rCDI may inform management of the disease. We describe a post hoc comparison of GI microbiome and bile acid profiles between patients with frCDI and mrCDI in a Phase 3 open-label trial, ECOSPOR IV, of fecal microbiota spores, live-brpk (VOWST®; VOS, formerly SER-109), an orally-administered live microbiome therapeutic.

METHODS: Patients received VOS following symptom resolution after standard-of-care antibiotics. Pretreatment baseline (within 3 days following antibiotic completion) and Week 1 post-dosing stool samples were collected for whole metagenomic sequencing and metabolomics. Diversity was calculated from MetaPhlAn2 species profiles. Concentrations of primary and secondary BAs were measured via targeted LC-MS/MS.

RESULTS: rCDI rates through Week 8 were similarly low in both frCDI and mrCDI patients (6.5% versus 9.7%, respectively). Baseline microbial diversity was similarly low between frCDI and mrCDI subgroups (P > .05). Diversity and secondary BA concentrations increased in both subgroups, whereas primary BA concentrations declined following VOS dosing, leading to few differences between subgroups at Week 1.

CONCLUSIONS: These data suggest commonalities in microbiome disruption in patients with frCDI and mrCDI that contribute to recurrence and suggest that antibiotics followed by a live microbiome therapy may be an optimal treatment strategy for rCDI, regardless of number of prior CDI recurrences.},
}

Humans
*Bile Acids and Salts/analysis/metabolism
*Gastrointestinal Microbiome
*Clostridium Infections/microbiology/drug therapy/therapy
Male
Female
Feces/microbiology/chemistry
Middle Aged
*Clostridioides difficile
Aged
Recurrence
Anti-Bacterial Agents/therapeutic use
Adult
Fecal Microbiota Transplantation

@article {pmid41223536,
year = {2025},
author = {Toresson, L and Ludvigsson, U and Olmedal, G and Hellgren, J and Toni, M and Giaretta, PR and Suchodolski, JS and Blake, AB},
title = {Repeated fecal microbiota transplantation in dogs with chronic enteropathy can decrease disease activity and corticosteroid usage.},
journal = {Journal of the American Veterinary Medical Association},
volume = {},
number = {},
pages = {1-10},
doi = {10.2460/javma.25.08.0563},
pmid = {41223536},
issn = {1943-569X},
abstract = {OBJECTIVE: Evaluate clinical and fecal parameters in dogs with refractory chronic enteropathy (CE) treated with repeated fecal microbiota transplantation (FMT) as adjunct treatment.

METHODS: This was a prospective longitudinal observational study from September 25, 2021, to June 20, 2024. Thirty-nine dogs received 2 to 3 rectal FMTs over 1 month. Canine inflammatory bowel disease activity index (CIBDAI) and fecal samples were assessed for 6 months. Fecal samples were analyzed for dysbiosis index, bile acids, and calprotectin.

RESULTS: 28 of 39 dogs responded to FMT. Eight dogs had a short-lasting response. Before FMT, baseline CIBDAI was equivalent in responders and nonresponders. Responders had a significantly decreased CIBDAI at 1 month, which remained unaltered at 6 months in long-lasting responders (LLRs). Baseline dysbiosis index (mean [95% CI]) was significantly lower in LLRs (-0.02 [-3.3 to 2.7]) versus nonresponders and short-lasting responders combined (N/SRs; 2.9 [-0.2 to 6.0]). Baseline percentage of secondary unconjugated fecal bile acids was higher in LLRs (65 [41 to 89]) versus N/SRs (30 [6 to 54]). Dysbiosis index decreased significantly at the time point for the third FMT in LLRs (-2.4 [-3.9 to 2.2]) but not in N/SRs (3.3 [-0.4 to 5.7]). Corticosteroid tapering was achieved in 13 responders. Mild adverse events were noted in 4 dogs.

CONCLUSIONS: This repeated FMT protocol was an effective adjunct treatment in refractory CE dogs, especially in dogs with no or mild dysbiosis. Marked dysbiosis and BA dysmetabolism before and after FMT appeared associated with no clinical response or a short-lasting response to FMT, potentially requiring repeated FMT.

CLINICAL RELEVANCE: Repeated FMT could reduce disease activity and corticosteroid usage in dogs with refractory CE.},
}

@article {pmid41220843,
year = {2025},
author = {Kwon, K and Kim, M and Jung, Y and Yoon, MY and Lee, JY and Yoon, SS and Rho, M and Chung, YW and Ryu, JH},
title = {Intestinal Dysbiosis Caused by Epithelial Fabp6 Gene Disruption Exacerbates Gut Inflammatory Disease.},
journal = {Immune network},
volume = {25},
number = {5},
pages = {e35},
pmid = {41220843},
issn = {1598-2629},
abstract = {Ileal lipid binding protein (Ilbp), encoded by Fabp6 gene, plays a critical role in intracellular transport of bile acids (BAs) from apical to basolateral side of ileal enterocytes, maintaining BA homeostasis within enterohepatic circulation. However, pathophysiological consequences of Ilbp deficiency remain largely unexplored. Here, we demonstrate that disruption of BA balance, caused by intestinal epithelial cell (IEC)-specific Fabp6 gene knockout (Fabp6 [ΔIEC]), exacerbates dextran sulfate sodium (DSS)-induced gut inflammation. Fecal microbiota transplantation from Fabp6 [ΔIEC] mice to germ free recipient mice replicated the adverse effects observed in Fabp6 [ΔIEC] mice, which were mitigated when these mice were co-housed with control (Fabp6 [f/f]) mice. Metagenomic analysis identified Ligilactobacillus murinus as a primarily diminished strain in Fabp6 [ΔIEC] mice. Oral administration of L. murinus isolated from feces of Fabp6 [f/f] mice ameliorated DSS-induced colitis in Fabp6 [ΔIEC] mice by restoring epithelial barrier integrity and lowering pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. Furthermore, daily administration of taurodeoxycholic acid-one of the BAs reduced in Fabp6 [ΔIEC] mice and that promotes the growth of L. murinus in an in vitro growth assay-also exhibited a protective effect against DSS-induced colitis through a similar mechanism. These findings suggest that deficiency of specific BAs due to epithelial Fabp6 deletion leads to gut dysbiosis, predisposing the host to inflammatory disease.},
}

@article {pmid41219783,
year = {2025},
author = {Sami, A and Ashraf, R and Nisar, S and Mustehsan, ZH and Javed, MA and Ozsahin, DU and Waheed, Y},
title = {A comprehensive narrative review on precision medicine approach to hypertension: exploring the role of genetics, epigenetics, microbiome, and artificial intelligence.},
journal = {Journal of health, population, and nutrition},
volume = {44},
number = {1},
pages = {394},
pmid = {41219783},
issn = {2072-1315},
abstract = {Hypertension (HTN) impacts approximately 1.28 billion individuals globally and poses a great burden of disease. The objectives of this study are to explore the role of genetics, epigenetics, microbiome, and artificial intelligence (AI) in the management of HTN. A thorough literature search was conducted across various databases including PubMed, Google Scholar, Web of Science (WoS), and Medline to retrieve articles related to the role of genetics, epigenetics, microbiome, and AI in the precision medicine of HTN. Genes-including ACE, NOS3, ADD1, CYP11B2, NPPA, and NPPB-have a profound impact on blood pressure (BP) regulation in our body and polymorphism in these key genes can lead to HTN. Up or down-regulation of genes by epigenetic factors such as miRNA-155, miRNA-210, and miRNA-122 can significantly contribute to the development of HTN. These genetic and epigenetic factors can also be used as specific targets for gene editing and gene therapy for long-term management of HTN. However, the implementation of these techniques has not been possible in clinical settings due to lack of human studies and safety concerns related to unpredictable DNA alterations, nucleotide deletions, and loss of allele-specific chromosomes. Modulation of gut microbiome through oral supplements, fecal microbiota transplant (FMT), and dietary interventions has emerged as one the most effective and safe techniques for managing HTN in human models. AI-based cutting-edge models have helped curate personalized diet plans based on an individual's unique microbiome, genomic information, and physiological conditions leading to a reduction in BMI, fat, BP, and heart rate while improving overall cardiac health and gut microbial diversity. Despite the significant advantages offered by AI-based medicine, ethical concerns-related to data privacy, bias, and discrimination-and ineffective models have led to limited integration of AI in precision medicine of HTN. The integration of genetics, epigenetics, microbiome, and AI-based models can play a key role in improving the current landscape of precision medicine of HTN. These cutting-edge techniques can lead to a shift from the current one-size-fits all approach to more personalized treatment plan however further research in human models is needed to determine the safety and true efficacy of these techniques. Additionally, new AI-models need to be developed that address ethical concerns and are effective in real-world clinical settings.},
}

@article {pmid41219653,
year = {2025},
author = {Lamba, JK and Tandon, C and Tandon, S},
title = {Gut Microbiota and Chronic Kidney Disease: A Complex Interplay with Implications for Diagnosis and Treatment.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41219653},
issn = {1867-1314},
abstract = {Chronic kidney disease (CKD) progresses over the years with a steady loss of renal function, often culminating in renal failure. While diabetes and hypertension are the major drivers, the exact underlying molecular mechanism for CKD remains only partially understood. Emerging research has revealed a new paradigm, linking microbiota imbalance or dysbiosis with CKD. Dysbiosis leads to the development of uremic toxins, which aggravate kidney damage, inflammation, and metabolic disruptions that accelerate disease progression. This review explores the complex interactions between dysbiosis, uremic toxins, and the major risk factors, namely, diabetes and hypertension. Microbiome-targeted interventions, such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), are discussed with an emphasis on their therapeutic relevance in influencing renal health. Additionally, the potential of genetic engineering, particularly CRISPR-based systems, to develop 'smart bacteria' designed to restore gut health is also examined. Future perspectives highlight the need for personalized therapies targeting the gut-kidney axis. Incorporating microbiome modulation into standard CKD treatments holds the potential to slow disease progression, enhance recovery, and improve the quality of life for patients.},
}

@article {pmid41217998,
year = {2025},
author = {Wei, Q and Rui, M and Wang, Y and Ng, SC and You, JHS},
title = {Cost-effectiveness analysis of fecal microbiota transplantation for patients with irritable bowel syndrome.},
journal = {Digestion},
volume = {},
number = {},
pages = {1-21},
doi = {10.1159/000549485},
pmid = {41217998},
issn = {1421-9867},
abstract = {BACKGROUND AND AIM: Studies have demonstrated clinical benefits of fecal microbiota transplantation (FMT) for treatment of irritable bowel syndrome (IBS). This study aimed to evaluate the cost-effectiveness of FMT versus standard drug treatment for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.

METHODS: Two one-year Markov models were developed to examine the outcomes of FMT versus standard drug treatment in patients with constipation-predominant IBS (IBS-C) and diarrhea-predominant IBS (IBS-D). The primary model outcomes included direct medical cost and quality-adjusted life-years (QALYs) gained. Model inputs were obtained from literature and public data. Sensitivity analyses were performed to examine the robustness of model results.

RESULTS: In the base-case analysis, FMT gained higher QALYs (by 0.0159 QALYs for IBS-C and 0.0166 QALYs for IBS-D) with cost-savings (USD7,813 for IBS-C and USD8,979 for IBS-D) when compared to standard drug treatment. Key influential parameters identified by one-way sensitivity analysis were response probabilities of FMT and first-line treatment, the utility values of therapeutic response and nonresponse, and FMT cost. The probabilities of FMT to be accepted as the preferred strategy at a willingness-to-pay threshold of 50,000 USD/QALY were 99.91% and 99.89% for IBS-C and IBS-D, respectively.

CONCLUSIONS: FMT appears to be cost-effective for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.},
}

@article {pmid41216880,
year = {2025},
author = {Gu, C and Xu, R and Yin, B and Wu, R and Wei, Y and Wang, D and Wei, W},
title = {Sex-Specific Involvement of Gut Microbiota in Behavioral and Endocrine Responses to Chronic Predator Odor in Brandt's Voles.},
journal = {Integrative zoology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1749-4877.13014},
pmid = {41216880},
issn = {1749-4877},
support = {32401290//National Natural Science Foundation of China/ ; 31770422//National Natural Science Foundation of China/ ; //the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; },
abstract = {Predator cues have profound impacts on the behavior and physiology of prey animals. However, the mechanisms underlying stress responses induced by chronic exposure to predator cues in mammals, particularly the role of the gut microbiota, remain insufficiently understood. This study investigated how gut microbiota contributes to behavioral and physiological responses in Brandt's voles (Lasiopodomys brandtii) under chronic predator odor exposure. Adult voles were repeatedly exposed to cat feces odor (CO) for 18 days (1 h/day), followed by behavioral tests to assess anti-predator and anxiety-like behaviors, hormonal measurements to evaluate basal hypothalamic-pituitary-adrenal (HPA) axis activity, and 16S rRNA sequencing to analyze gut microbiota composition. The results showed that repeated CO exposure increased anxiety-like behaviors and basal HPA axis activity in both sexes. However, anti-predator behaviors exhibited sex-specific responses: Males were habituated to repeated CO exposure by reducing freezing and alerting behaviors, whereas females consistently displayed concealing strategies, reflecting different adaptive strategies to prolonged predator threats. While CO exposure did not alter the α-diversity of gut microbiota, it significantly affected the β-diversity in females, including a reduction in the relative abundance of Treponema and Quinella. Cecal microbiota transplantation from female CO-exposed voles to naive recipients increased anxiety-like behaviors and basal HPA levels but did not alter anti-predator behaviors in the recipients. In contrast, male recipients showed no significant behavioral or physiological changes. These findings suggest that gut microbiota is involved in regulating anxiety-like behavior and HPA axis activity in female voles but has a limited regulating role in male voles.},
}

@article {pmid41214728,
year = {2025},
author = {Tang, X and You, X},
title = {Progress and prospects of gut microbiota-targeted therapy for primary biliary cholangitis.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {86},
pmid = {41214728},
issn = {1757-4749},
abstract = {Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease. Current therapeutic options are limited, with some patients responding poorly to first-line treatment with ursodeoxycholic acid. However, second-line drugs are difficult to develop. There are no drugs available to treat liver dysfunction. Currently, the etiology of PBC is unknown, and the intestinal flora affects the liver through the gut‒liver axis. The hypothesis of intestinal dysbiosis has gradually been accepted and involves mechanisms such as leaky gut, abnormal bile acids metabolism, and dysregulated immune tolerance. We found that gut microbiota-targeted therapy, including antibiotics, dietary regulation, probiotic supplementation, and fecal microbiota transplantation, can effectively improve liver function, remodel the intestinal microbiota, and alleviate symptom. However, this therapy has limitations, such as large individual differences and unknown long-term efficacy and safety. Large-scale and long-term clinical studies are expected to promote the broad application of gut microbiota-targeted therapy in the clinic.},
}

@article {pmid41212912,
year = {2025},
author = {Zhao, C and Ming, S and Zhang, J and Huang, T and Du, Y and Liu, J and Zong, S},
title = {Alleviative Effect of Stropharia rugosoannulata Exopolysaccharide on d-Galactose-Induced Gut Inflammation and Oxidative Stress by Modulating Gut Microbiota.},
journal = {Chemistry & biodiversity},
volume = {},
number = {},
pages = {e02918},
doi = {10.1002/cbdv.202502918},
pmid = {41212912},
issn = {1612-1880},
support = {137012023//Yangzhou University/ ; BY20221437//Joint Project of Industry-University-Research of Jiangsu Province/ ; },
abstract = {The exopolysaccharide SREP-1, purified from the fermentation broth of Stropharia rugosoannulata, exhibited antiaging potential. As aging significantly alters gut structure and function, protective effect of SREP-1 was investigated using a d-galactose-induced aging mouse model. SREP-1 administration reversed D-galactose-induced body weight loss and colon damage, as evidenced by improved histopathology. SREP-1 mitigated weight loss and colon damage, enhanced the activities of antioxidants (SOD, GSH-Px, and CAT), and reduced the level of MDA. It decreased proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and elevated IL-10 in colon tissue, while boosting serum immunoglobulins (IgG and IgM). Crucially, these effects were abolished by antibiotic pretreatment, highlighting the role of gut microbiota in SREP-1 bioactivity. This role was further confirmed through fecal microbiota transplantation (FMT) and fecal supernatant transplantation (FST) experiments. Based on 16S rRNA sequencing, SREP-1 restored gut microbial diversity, increased beneficial genera (e.g., Faecalibacterium, Akkermansia, Lactobacillus, and Bacteroides), and decreased harmful bacteria (e.g., Escherichia-Shigella and Collinsella). Furthermore, short-chain fatty acids (SCFAs) levels were elevated in the SREP-1 group, which might regulate GPCRs/NF-κB/Nrf2 signaling pathways and exert biological activity. This study revealed the potential of SREP-1 to alleviate aging-related intestinal dysfunction and underscored the crucial role of gut microbiota in mediating these effects.},
}

@article {pmid41211636,
year = {2025},
author = {Wu, L and Zhang, Q and Tang, Z and Li, Y and Wu, T and Chen, L and Tan, C and Zhang, L and Ji, X and Zhang, S and Wu, Y and Bozec, A and Zaiss, MM and Luo, Y},
title = {Gut microbiota-derived tryptophan indole metabolites ameliorate collagen-induced arthritis in mice via aryl hydrocarbon receptor activation in T cells and intestinal epithelial cells.},
journal = {Arthritis & rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43430},
pmid = {41211636},
issn = {2326-5205},
abstract = {OBJECTIVE: To investigate the specific role of tryptophan metabolism, especially that of microbiome-derived metabolites, in the development of rheumatoid arthritis (RA).

METHODS: We employed metabolomics to profile metabolites in 53 high-risk for RA individuals (PreRAs), 30 established RA patients and 38 healthy individuals. Fecal microbiota transplantation (FMT) and collagen-induced arthritis (CIA) mouse models were used to investigate the impact of gut microbiome on arthritis severity, gut barrier function, and metabolic change. Treg cell differentiation and epithelial cells' barrier function were assessed by flow cytometry, immunofluoresence staining and western blotting. Co-immunoprecipitation and luciferase were applied for molecular mechanism studies.

RESULTS: Dysregulated tryptophan metabolism exists in RA and PreRA individuals, as well as in FMT mice, characterized by a shift toward the kynurenine pathway and reduced activity of serotonin and indole pathways. Indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) significantly alleviated arthritis in CIA mice by expanding Treg cells via the classical aryl hydrocarbon receptor (AhR)-aryl hydrocarbon receptor nuclear translocator (ARNT)-xenobiotic response element (XRE) signaling pathway. Moreover, ILA repaired the leaking gut by increasing Zo-1 and occludin expression in Caco-2 cells, which was blocked by AhR antagonist CH223191. Moreover, CH223191 treatment could significantly reverse the improving effects of ILA and IAA on arthritis in mice.

CONCLUSION: These findings indicate that Trp indole metabolites may play a negative regulatory role in the progression of RA by affecting Treg cell development and intestinal gut barrier function.},
}

@article {pmid41208872,
year = {2025},
author = {Sun, J and Chen, J and Shen, Y and Yao, X and Sun, H and Chen, B and Feng, J},
title = {Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1689522},
pmid = {41208872},
issn = {1663-9812},
abstract = {Diabetes mellitus (DM), a globally prevalent metabolic disorder, poses a significant public health threat due to its systemic complications. Recent studies have increasingly recognized the lung as a target organ in diabetic pathology. However, owing to the respiratory system's complex physiology, the mechanisms underlying DM-associated lung injury remain poorly understood and require further investigation. This review systematically elucidates the multifaceted effects of DM-induced metabolic disturbances on the lung, with a focus on four key pathophysiological axes triggered by hyperglycemic homeostasis, including chronic inflammation, oxidative stress imbalance, endocrine network disruption, and intestinal dysbiosis. Building upon the "metabolism-microbiota-immune" axis framework, this study demonstrates that: persistent hyperglycemia induces pulmonary tissue damage and immune microenvironment disruption through metabolite accumulation and mitochondrial dysfunction; DM-associated intestinal dysbiosis amplifies pulmonary inflammation via the gut-lung axis, mediated by metabolic reprogramming and immune cell trafficking; and metabolic aberration-driven dysregulation of innate/adaptive immunity serves as the pivotal mediator for progressive lung injury. Building on this mechanistic framework, we discuss emerging therapeutic avenues that target metabolic reprogramming, modulation of the gut microbiota, and restoration of immune homeostasis. Promising strategies include repurposed antidiabetic drugs (e.g., SGLT-2 inhibitors, GLP-1 receptor agonists), microbiome-targeted therapies (e.g., fecal microbiota transplantation), and novel immunomodulatory agents. These therapies are offering a new shift towards multi-target treatments for diabetic pulmonary complications.},
}

@article {pmid41208121,
year = {2025},
author = {Calhoun, AC and Shosanya, T and Long, BK and Rehberger, JK and Sadd, BM},
title = {Host-associated beneficial gut microbiota boosts induced immunity and limits immune deployment costs in bumblebees.},
journal = {The Journal of animal ecology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1365-2656.70180},
pmid = {41208121},
issn = {1365-2656},
support = {F22AP02271//U.S. Fish and Wildlife Service/ ; R15GM12968/NH/NIH HHS/United States ; },
abstract = {Ecological immunology posits that variation in host resistance to infection may be attributed partly to the ecological and evolutionary costs of immunity. While the deployment of immune defence is necessary to combat pathogenic infection, hosts pay energetic and other costs for activation. Host-associated beneficial microbiota have been shown to affect multiple host traits, including immunity, but how interactions with these microbial communities may mitigate the costs of immune activation remains an open question. For apid bees, including eusocial bumblebees, core members of the adult gut microbiota contribute to a variety of fitness-relevant traits and provide a key ecological and evolutionary relationship contributing to ecological success. Here we test the hypothesis that the host-associated microbiota provides benefits to bumblebee immunity, including the mitigation of the costs associated with inducible immune responses. Freshly emerged germ-free adult workers were supplemented with their native microbiota via experimental faecal transplants from nestmates or kept deprived of their native microbiota inoculum. We assessed functional measures of induced immunity and assessed the costs of non-pathogenic immune activation for survival. In support of our hypothesis, we find that microbiota supplementation strengthened functional antibacterial immunity. Moreover, although we observed a cost of immune activation for survival, the cost was much greater for bees deprived of their native gut microbiota compared to those supplemented. Thus, we provide evidence that in addition to other roles, the microbiota mitigates costs of immune deployment. This demonstrates a key role for host-associated microbiota in the realization of induced immune defence, and contributes more broadly to our understanding of microbiota-immune interactions in the context of ecological immunology.},
}

@article {pmid41207269,
year = {2025},
author = {Xu, M and Fu, Q and Liu, J and Chen, J and Zhai, X and Wang, C and Xu, W and Li, L and Wang, K and Si, H},
title = {Shouhui Tongbian capsule promotes calcium absorption by regulating gut microbiota and protects against osteoporosis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157520},
doi = {10.1016/j.phymed.2025.157520},
pmid = {41207269},
issn = {1618-095X},
abstract = {BACKGROUND: Postmenopausal osteoporosis (OP) is a global health problem whose occurrence is strongly associated with intestinal flora dysbiosis. Shouhui Tongbian Capsule (SH) regulates gut microbiota for constipation/obesity, but its role, ability to counter calcium's side effects, and OP-related mechanism remain unclear.

PURPOSE: This study aimed to investigate the therapeutic effect of SH on OP and elucidate its mechanism in improving bone metabolism via gut microbiota regulation.

METHODS: Ovariectomized (OVX) mice received SH and/or calcium supplements. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and functional annotations were performed using the Kyoto Encyclopedia of Genes and Genomes database. Gut barrier function was assessed through histology, tight junction protein expression, and serum biomarkers. Micro-CT was used to quantify the bone microstructure. Fecal microbiota transplantation (FMT) validated the microbiota-dependent effects. Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed by calcium deposition staining and western blotting.

RESULTS: SH restored gut barrier integrity, reduced systemic inflammation, and alleviated constipation. SH reshaped the gut microbiota composition, enriched Lactobacillus, Lachnospiraceae, and Akkermansia, and strengthened metabolic pathways related to mineral absorption. SH synergized with calcium supplementation to significantly enhance bone mass in OVX mice. FMT experiments recapitulated the osteoprotective effects of SH, with calcium supplementation being a necessary factor in this process. SH potentiated the osteogenic capacity of BMSCs while having no effect on osteoclast differentiation.

CONCLUSION: SH ameliorates OP via the "microbiota-mineral absorption-osteogenesis" network by alleviating calcium-induced intestinal dysbiosis and promoting bone formation. This study is the first to confirm SH's synergistic regulation of gut microbiota and calcium metabolism against OP, offering novel insights for gut-bone axis-based OP therapies and highlighting traditional Chinese medicine's innovative potential in metabolic bone diseases.},
}

@article {pmid41206510,
year = {2025},
author = {Fang, J and Fang, J},
title = {A Review of Recent Advances in Fecal Microbiota Transplantation for the Treatment of Hepatic Encephalopathy.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {31},
number = {},
pages = {e949286},
doi = {10.12659/MSM.949286},
pmid = {41206510},
issn = {1643-3750},
abstract = {Hepatic encephalopathy (HE) results from a debilitating complication of liver cirrhosis and acute liver failure, characterized by neuropsychiatric abnormalities ranging broadly from mild cognitive impairment to respiratory failure to coma. The pathogenesis of HE is multifactorial, with gut-derived toxins, particularly ammonia, playing a central role. Recent advances in understanding the gut-liver-brain axis have revealed the importance of gut microbiota and dysbiosis in the development and progression of HE. Fecal microbiota transplantation (FMT), a clinical procedure that is performed to transfer fecal microbiota from a healthy donor to a patient with HE (recipient), has emerged as a promising therapeutic strategy for modulating gut microbiota and ameliorating HE. FMT facilitates the restoration of gut microbiota composition with increased microbial alpha diversity, reestablishment of the balance between beneficial and pathogenic bacteria, reduction in the production of gut-derived toxins, and improvement of intestinal barrier function. It also modulates immune and inflammatory responses, alleviating hepatocyte and biliary injury. FMT has also demonstrated efficacy in improving cognitive function and reducing hospitalizations in HE patients and can maintain a stable donor-like microbiota profile for up to 12 months post-transplantation. FMT is generally well-tolerated, with most adverse events reported to be mild and transient, providing a desirable option for HE treatment. This review provides a comprehensive overview of the current understanding of the role of gut microbiota in the pathogenesis of HE, the mechanisms underlying the therapeutic effects of FMT, and the clinical evidence supporting its use in HE. We will also discuss the limitations, challenges, and future prospects for FMT in the treatment of HE.},
}

@article {pmid41206275,
year = {2025},
author = {Hattoufi, K and Raji, F and Tligui, H and Benlhachemi, S and Heikel, J and Aguenaou, H and Barkat, A},
title = {Association of gut microbiota and type of feeding: Molecular analysis of a cohort of preterm moroccan newborns.},
journal = {Pediatrics and neonatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pedneo.2025.04.008},
pmid = {41206275},
issn = {2212-1692},
abstract = {BACKGROUND: We assessed the newborns' intestinal microbiota during the first three weeks of life using molecular biology techniques to understand colonization patterns according to feeding type.

METHODS: We conducted a prospective, observational descriptive study at the National Reference Centre for Neonatology and Nutrition, in collaboration with the research laboratory of the Children's Hospital at the University Hospital Centre Ibn Sina in Rabat. Stool samples were collected from 29 preterm newborns upon admission to the neonatal unit and subsequently twice weekly over a three-week period. Microbial composition was analyzed using real-time polymerase chain reaction (RT-qPCR), targeting four phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria.

RESULTS: The gestational age of the included preterm infants ranged from 28 to 36 weeks of amenorrhea. Enteral nutrition was initiated between the second and sixth days after birth. None of the infants was nursed immediately after birth or during their hospitalization. However, in 79 % of cases, breast milk was collected at home for later use in feeding the newborns, and among these, 21 % received more than 50 % of the collected breast milk. Over the first two weeks of life, Lactobacillus spp. was only detected in infants nursed by both breast milk and formula milk. Enterococcus spp. was present in all breastfed infants. Clostridium difficile and Clostridium perfringens were found in 83 % of formula-fed newborns in the second week of life and in all newborns by the end of the third week.

CONCLUSION: Promoting breastfeeding whenever possible is crucial for fostering a healthy gut microbiota. When breastfeeding is not feasible, incorporating infant formulas supplemented with probiotics and/or prebiotics can help establish a microbiota similar to that of breastfed infants. Additional preventive strategies, such as vaginal or fecal microbiota transplantation, may be considered, particularly for infants born via caesarean section.},
}

@article {pmid41206121,
year = {2025},
author = {Dong, PY and Chen, Y and Li, L and Zhai, CL and Yan, YC and Bai, Y and Li, YY and Dong, Y and Liu, J and Zhang, M and Liu, YH and Zhang, XF},
title = {Deoxynivalenol Disrupts Male Mice Reproduction through Gut-Testis Axis Dysregulation and Metabolic Alterations.},
journal = {Toxicological sciences : an official journal of the Society of Toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1093/toxsci/kfaf155},
pmid = {41206121},
issn = {1096-0929},
abstract = {The mycotoxin deoxynivalenol (DON) is a widespread contaminant that threatens male reproductive health, though the systemic mechanisms involving the gut-testis axis remain incompletely understood. We employed a multi-omics approach-integrating transcriptomics, 16S rRNA sequencing, and serum metabolomics-in a mouse model to investigate these mechanisms. Oral exposure to DON (2 mg/kg/day for two weeks) induced testicular damage and disrupted the blood-testis barrier, marked by the downregulation of Occludin and GJA1, alongside the suppression of steroidogenesis-related genes and proteins including StAR and CYP17A1. Concurrently, DON triggered gut microbiota dysbiosis, characterized by an increased abundance of Desulfovibrio and a decline in beneficial bacteria. Serum metabolomics further identified a significant depletion of key fatty acids and the cholesterol precursor 5Alpha-Cholestanol. Crucially, fecal microbiota transplantation from DON-treated mice reproduced testicular damage and suppressed steroidogenesis in recipient animals, directly establishing the causal role of gut microbiota in DON-induced reproductive toxicity. These findings collectively demonstrate that DON impairs male reproductive function by inducing gut microbiota dysbiosis and associated metabolic alterations. This work advances our understanding of the gut-testis axis in toxicology and provides mechanistic insights for mitigating mycotoxin-induced reproductive dysfunction.},
}

@article {pmid41206012,
year = {2025},
author = {Tan, EK and Wang, JDJ and Pettersson, S and Wang, Q and Takahashi, R and Poewe, W and Jankovic, J and Rascol, O},
title = {Faecal microbiota transplant for Parkinson's disease: promises and future directions.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf419},
pmid = {41206012},
issn = {1460-2156},
abstract = {There is considerable evidence linking alterations in gut microbiome composition with Parkinson's disease (PD), leading to several recent randomized controlled fecal microbiota transplantation (FMT) trials in PD patients targeting gut dysbiosis with the aim to modulate the gut-brain axis. Some FMT trials have observed motor and non-motor symptoms improvements in PD patients, possibly through microbiota linked enhanced short-chain fatty acid or other metabolite effects and reduced systemic inflammation. While the findings are exciting and can potentially open a new treatment paradigm, crital questions on donor selection, the optimal screening and selection of the donor microbiome, delivery routes and the timing and frequency of transplantation need to be addressed. We suggest that future FMT trials should incorporate blood, metabolites, urine and functional neuroimaging biological markers and control dietary, lifestyle comorbidities, medication intake and/or other potential variables, and to ensure optimal evaluation of interactions between the gut microbes and brain outcomes prospectively over a longer time frame.},
}

@article {pmid41205107,
year = {2025},
author = {Caron, B and Sequier, L and Dignass, A and Ghosh, S and Hart, A and Jairath, V and Kobayashi, T and Kotze, PG and Lakatos, PL and Louis, E and Magro, F and Sebastian, S and Solitano, V and Sidhu, S and Danese, S and Peyrin-Biroulet, L},
title = {Management of Patients with Ulcerative Proctitis: A Global Survey.},
journal = {Digestive diseases and sciences},
volume = {},
number = {},
pages = {},
pmid = {41205107},
issn = {1573-2568},
abstract = {UNLABELLED: BACKGROUND AND AIM: Ulcerative proctitis affects approximately 30% of patients with ulcerative colitis. Disease control is essential to maintain quality of life and to prevent disability and disease progression. The aim of this study was to investigate current practice on isolated proctitis management across the globe.

METHODS: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between January and February 2025.

RESULTS: The survey included 460 physicians from 66 countries. Most participants (87.9%) assessed clinical activity of isolated proctitis within 3 months of treatment initiation, 75.9% used fecal calprotectin, and 67.1% used C-reactive protein to measure disease activity. Endoscopic assessment was performed 3 to 6 months (34.2%) or 6 to 12 months (48.4%) after treatment induction. In this survey, 49% of participants were more reluctant to begin an advanced therapy in patients with isolated proctitis compared to pancolitis or left-sided colitis. About two-thirds of participants were less likely to use biologics in combination with immunosuppressants in isolated proctitis compared to left-sided or pancolitis. Anti-TNF (tumor necrosis factor) was the preferred choice in first-line advanced therapy after failing conventional treatment (48.4%).

CONCLUSION: This study highlighted differences in management of isolated proctitis compared to left-sided colitis or pancolitis. This is likely explained by the fact that isolated proctitis patients were historically excluded from clinical trials; therefore, management relied on extrapolation of data from studies on more extensive disease.},
}

@article {pmid41204332,
year = {2025},
author = {Pala, B and Frank, G and Pennazzi, L and Di Renzo, L and Gualtieri, P and Tocci, G and Rubattu, S},
title = {The role of gut microbiota in hypertension-mediated organ damage (HMOD): a systematic review.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1242},
pmid = {41204332},
issn = {1479-5876},
support = {PNRR-MAD-2022-12376295, CUP: F33C22001010006.//Seventh Generation Fund for Indigenous Peoples/ ; },
mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Hypertension/microbiology/complications/pathology/physiopathology ; Animals ; Dysbiosis ; },
abstract = {Hypertension (HTN), a multifactorial condition and major modifiable risk factor for cardiovascular disease, has been increasingly linked to gut microbiota (GM) alterations, encouraging investigation into its potential role in the progression of hypertension-mediated organ damage (HMOD). This systematic review aims to evaluate the role of GM in HTN pathophysiology and its contribution to HMOD, with the aim of identifying potential microbiota-related targets for personalized therapeutic strategies. The study, registered in PROSPERO and conducted according to PRISMA guidelines, involved a comprehensive search of five databases up to January 2025, selecting human and complementary animal studies investigating the relationship between GM, HTN, and HMOD. While few studies directly assessed HMOD, emerging evidence suggests a protective role of GM and its metabolites against cardiovascular, cerebral and renal injury. Heterogeneity in design, small sample sizes and a lack of standardized methodologies limited comparability therefore we did not perform a meta-analysis. In conclusion, GM dysbiosis and its metabolites are increasingly recognized as key providers to HMOD, offering encouraging targets for future preventive and therapeutic strategies. A substantial proportion of the available evidence originates from preclinical animal studies. While these findings provide valuable mechanistic insights, further longitudinal and interventional research in human populations is warranted to confirm their translational relevance.},
}

*Gastrointestinal Microbiome/physiology
Humans
*Hypertension/microbiology/complications/pathology/physiopathology
Animals
Dysbiosis

@article {pmid41203044,
year = {2025},
author = {Jagwani, S and Musumeci, L and Flores, L and Mackenzie, GG and Amiji, MM},
title = {Strategic modulation of the gastrointestinal microbiome to enhance pancreatic cancer immunotherapy.},
journal = {Drug discovery today},
volume = {},
number = {},
pages = {104528},
doi = {10.1016/j.drudis.2025.104528},
pmid = {41203044},
issn = {1878-5832},
abstract = {Pancreatic cancer (PC) remains one of the most lethal malignancies, characterized by aggressive progression, late detection, and limited response to current therapies. Recent research has revealed that the gastrointestinal and intratumoral microbiomes are key modulators of immune regulation, metabolism, and epigenetic pathways, influencing tumor progression and therapeutic efficacy. This review summarizes the complex microbiome-PC interplay, emphasizing microbial modulation of inflammation, immunity, and treatment resistance. We also highlight microbiome-targeted strategies, such as probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, along with advanced drug-delivery platforms - including nanoparticles, engineered bacteria, and stimuli-responsive systems - for precise microbiome modulation. Integrating microbiome science with immunotherapy, nanotechnology, and epigenetic reprogramming offers promising opportunities to improve outcomes in PC.},
}

@article {pmid41202150,
year = {2025},
author = {Champagne-Jorgensen, K and Gommerman, JL},
title = {Two of a kind, one with MS: Gut microbes tip the balance.},
journal = {Science immunology},
volume = {10},
number = {113},
pages = {eaed4910},
doi = {10.1126/sciimmunol.aed4910},
pmid = {41202150},
issn = {2470-9468},
mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; Animals ; *Multiple Sclerosis/immunology/microbiology ; Mice ; Fecal Microbiota Transplantation ; },
abstract = {An MS twin study links ileal Lachnospiraceae to spontaneous CNS autoimmunity in mice receiving a human microbiome transplant.},
}

*Gastrointestinal Microbiome/immunology
Humans
Animals
*Multiple Sclerosis/immunology/microbiology
Mice
Fecal Microbiota Transplantation

@article {pmid41201220,
year = {2025},
author = {Wang, W and Li, J and Mu, L and Bai, Y and Zhu, M and Zhao, Y and Hu, S and Wang, J and Shao, P and Su, X},
title = {Vitamin K2 Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Mitochondrial Dysfunction Modulation via Gut Microbiota.},
journal = {International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition},
volume = {95},
number = {5},
pages = {37275},
doi = {10.31083/IJVNR37275},
pmid = {41201220},
issn = {0300-9831},
support = {82103810//National Natural Science Foundation of China/ ; 4457475042JZ2300U0//Outstanding Young Director in Air Force Medical University/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects ; Male ; *Vitamin K 2/pharmacology/administration & dosage ; Liver/pathology/drug effects/metabolism ; *Fatty Liver/drug therapy ; *Mitochondria/drug effects ; Disease Models, Animal ; *Non-alcoholic Fatty Liver Disease/drug therapy ; Dysbiosis ; },
abstract = {INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. Meanwhile, the development of MASLD is related to dysbiosis of the gut microbiota (GM). Our previous studies have shown that Vitamin K2 (VK2) has considerable potential to ameliorate mitochondrial dysfunction in mice fed a high-fat diet (HFD); however, the mechanism through which VK2 improves mitochondrial function and mitigates MASLD remains unclear.

OBJECTIVE: This study aimed to elucidate the mechanism through which VK2 modulates MASLD.

METHODS: A total of 80 C57BL/6J mice (4-5 weeks old) were fed a HFD for 16 weeks to establish the MASLD animal model. Additionally, VK2 was administered at a dose of 120 mg/kg/day for the last 8 weeks; 30 mice were fed a normal diet for the entire 24-week period. Mice were randomly divided into groups according to different experimental protocols. Hematoxylin and Eosin (H&E) staining, Oil Red O staining, and Cluster of Differentiation 11b (CD11b) immunofluorescence staining were used to detect liver histology and inflammatory cell infiltration in the mouse liver tissues. Moreover, 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation (FMT) were employed to investigate the microbiota-mediated anti-MASLD effects of VK2. Adeno-associated virus 9 (AAV9) was used to elucidate the mechanism through which VK2 regulates MASLD severity.

RESULTS: VK2 significantly reduced hepatic lipid (triacylglycerol (TG) and total cholesterol (TC)) levels, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in HFD-fed mice (p < 0.05). VK2 also significantly suppressed inflammatory responses (p < 0.05), oxidative stress (p < 0.05), and improved mitochondrial dysfunction (p < 0.05) in a GM-dependent manner. Furthermore, VK2 restored the balance in the intestinal microbiota primarily through regulating Lactobacillus spp. abundance, and markedly alleviated MASLD via a GM-dependent manner. VK2 notably upregulated the expression of SIRT3 signaling pathway proteins (p < 0.05), thereby reducing MASLD-associated mitochondrial dysfunction (p < 0.05).

CONCLUSIONS: VK2 exerts promising therapeutic effects mainly through enhancing intestinal Lactobacillus abundance and ameliorating mitochondrial dysfunction.},
}

Animals
*Gastrointestinal Microbiome/drug effects
Mice, Inbred C57BL
Mice
Diet, High-Fat/adverse effects
Male
*Vitamin K 2/pharmacology/administration & dosage
Liver/pathology/drug effects/metabolism
*Fatty Liver/drug therapy
*Mitochondria/drug effects
Disease Models, Animal
*Non-alcoholic Fatty Liver Disease/drug therapy
Dysbiosis

@article {pmid41199753,
year = {2025},
author = {Zulfatim, HS and Afrina, V and d'Arqom, A and Sutantyo, QE and Amornsupak, K and Nualkaew, T},
title = {Anti-Inflammatory Drugs for Alcoholic Liver Disease: A Systematic Review on Survival and Adverse Events.},
journal = {International journal of hepatology},
volume = {2025},
number = {},
pages = {8535952},
pmid = {41199753},
issn = {2090-3448},
abstract = {AIM: Alcoholic liver disease (ALD) is a major global health burden, with alcoholic hepatitis (AH) and severe alcoholic hepatitis (SAH) contributing significantly to mortality. Inflammation plays a central role in disease progression, and various anti-inflammatory therapies, particularly corticosteroids, have been employed to improve survival. However, clinical outcomes across different treatments vary. This systematic review is aimed at evaluating the effectiveness of anti-inflammatory pharmacological therapies compared to corticosteroids in improving short-term survival at 1, 3, and 6 months and to assess the incidence of adverse events in patients with ALD.

METHODS: The review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, Scopus, ScienceDirect, and Clarivate Web of Science using MeSH terms. Inclusion criteria consisted of full-text, open-access, English articles (2014-2024) that reported survival outcomes and adverse events in patients with ALD treated with corticosteroids versus alternative or adjunctive anti-inflammatory therapies. Studies lacking a corticosteroid comparator were excluded.

RESULTS: Nine randomized controlled trials (RCTs) involving patients with AH and SAH were included. The interventions compared to corticosteroids included pentoxifylline, anakinra, metadoxine, S-adenosylmethionine (SAMe), granulocyte colony-stimulating factor (G-CSF), rifaximin, and fecal microbiota transplantation (FMT) as monotherapies or combination regimens. Among anti-inflammatory therapies, combination therapy with corticosteroids and metadoxine significantly improves 3- and 6-month survival rates in patients with ALD. Similarly, corticosteroids combined with SAMe demonstrate efficacy in enhancing 1- and 6-month survival rates. Notably, the metadoxine-based combination regimen exhibited a superior safety profile, with fewer adverse events compared to other anti-inflammatory therapies evaluated in this review.

CONCLUSIONS: Even though corticosteroids remain the current standard of care for severe AH, this review suggests that certain combination therapies, particularly those involving metadoxine or SAMe, may offer some survival benefits. FMT also shows promise by potentially improving survival while maintaining a favorable safety profile. Among these, the metadoxine-based regimen has been explored as a promising therapeutic strategy in some contexts. However, these findings must be interpreted with caution. The evidence is limited by significant study heterogeneity and a lack of high-quality RCTs. These limitations underscore the critical need for well-powered, rigorous RCTs with standardized survival and safety outcomes.},
}

@article {pmid41199348,
year = {2025},
author = {Ghozlane, A and Thirion, F and Plaza Oñate, F and Gauthier, F and Le Chatelier, E and Annamalé, A and Almeida, M and Ehrlich, SD and Pons, N},
title = {Accurate profiling of microbial communities for shotgun metagenomic sequencing with Meteor2.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {227},
pmid = {41199348},
issn = {2049-2618},
support = {ANR-11-DPBS-0001//Metagenopolis/ ; },
mesh = {*Metagenomics/methods ; Animals ; Mice ; Humans ; *Microbiota/genetics ; *Bacteria/genetics/classification ; *Metagenome ; *Gastrointestinal Microbiome/genetics ; *Software ; Computational Biology/methods ; },
abstract = {BACKGROUND: The characterization of complex microbial communities is a critical challenge in microbiome research, as it is essential for understanding the intricate relationships between microorganisms and their environments. Metagenomic profiling has advanced into a multifaceted approach, combining taxonomic, functional, and strain-level profiling (TFSP) of microbial communities. Here, we present Meteor2, a tool that leverages compact, environment-specific microbial gene catalogues to deliver comprehensive TFSP insights from metagenomic samples.

RESULTS: Meteor2 currently supports 10 ecosystems, gathering 63,494,365 microbial genes clustered into 11,653 metagenomic species pangenomes (MSPs). These genes are extensively annotated for KEGG orthology, carbohydrate-active enzymes (CAZymes) and antibiotic-resistant genes (ARGs). In benchmark tests, Meteor2 demonstrated strong performance in TFSP, particularly excelling in detecting low-abundance species. When applied to shallow-sequenced datasets, Meteor2 improved species detection sensitivity by at least 45% for both human and mouse gut microbiota simulations compared to MetaPhlAn4 or sylph. For functional profiling, Meteor2 improved abundance estimation accuracy by at least 35% compared to HUMAnN3 (based on Bray-Curtis dissimilarity). Additionally, Meteor2 tracked more strain pairs than StrainPhlAn, capturing an additional 9.8% on the human dataset and 19.4% on the mouse dataset. Furthermore, in its fast configuration, Meteor2 emerges as one of the fastest available tools for profiling, requiring only 2.3 min for taxonomic analysis and 10 min for strain-level analysis against the human microbial gene catalogue when processing 10 M paired reads - operating within a modest 5 GB RAM footprint. We further validated Meteor2 using a published faecal microbiota transplantation (FMT) dataset, demonstrating its ability to deliver an extensive and actionable metagenomic analysis. The unified database design also simplifies the integration of TFSP outputs, making it straightforward for researchers to interpret and compare results.

CONCLUSIONS: These results highlight Meteor2 as a robust and versatile tool for advancing microbiome research and applications. As an open-source, easy-to-install, and accurate analysis platform, Meteor2 is highly accessible to researchers, facilitating the exploration of complex microbial ecosystems.},
}

*Metagenomics/methods
Animals
Mice
Humans
*Microbiota/genetics
*Bacteria/genetics/classification
*Metagenome
*Gastrointestinal Microbiome/genetics
*Software
Computational Biology/methods

@article {pmid41197688,
year = {2025},
author = {Mela, V and Ortiz Samur, NS and Vijaya, AK and Gálvez, VJ and García-Martín, ML and Bandera, B and Martínez-Montoro, JI and Gómez-Pérez, AM and Moreno-Indias, I and Tinahones, FJ},
title = {Ketogenic diet is less effective in ameliorating depression and anxiety in obesity than Mediterranean diet: A pilot study for exploring the GUT-brain axis.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106167},
doi = {10.1016/j.bbi.2025.106167},
pmid = {41197688},
issn = {1090-2139},
abstract = {Obesity is associated with depressive symptoms due to biological and psychological factors. Dietary interventions, including the Ketogenic (Keto) and Mediterranean (Med) diets, impact weight loss and mental health differently. While the Keto diet promotes rapid weight loss by increasing ketone body levels, its effects on mental health, particularly in individuals with obesity, remain unclear. This exploratory pilot study explores the impact of both diets on depression and impulsiveness, focusing on the gut-brain axis. Sixty-four participants (Body Mass Index 30-45 kg/m[2], ages 18-65) were randomly assigned to follow one of the two diets for three months. Due to attrition, 37 participants (Med n = 23; Keto n = 14) completed the study. Depression and impulsivity scores were evaluated before and after the intervention. Stool samples were collected for microbiota analysis, and faecal transplants were performed in healthy mice. Brain and serum metabolites in recipient mice were analysed using High-Resolution Magic Angle Spinning (HR-MAS) and Proton Nuclear Magnetic Resonance ([1]H NMR) spectroscopy. The Med diet showed greater improvement in depression scores compared to the Keto diet, while the latter was associated with reductions in impulsivity (urgency subscale). However, faecal transplants from the Keto group induced anxiety-like behaviours in recipient mice, which correlated with significant microbiota and metabolite changes. The Keto group exhibited increased levels of taurine, alanine, and betaine in the brain, and threonine levels were correlated with behavioural changes. These findings suggest that the Med diet offers more consistent short-term benefits related to depressive symptoms, while the Keto diet modulated impulsivity. The animal model findings highlighted the role of diet-induced microbiota changes and metabolite alterations in the gut-brain axis. Long-term studies in a larger population are needed to tailor dietary interventions, essential for optimizing mental and physical health in obesity.},
}

@article {pmid41196658,
year = {2025},
author = {Verna, G and De Santis, S and Islam, BN and Sommella, EM and Licastro, D and Zhang, L and De Almelda Celio, F and Miller, EN and Merciai, F and Caponigro, V and Xin, W and Campiglia, P and Pizarro, TT and Chieppa, M and Cominelli, F},
title = {A missense mutation in Muc2 promotes gut microbiome- and metabolome-dependent colitis-associated tumorigenesis.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI196712},
pmid = {41196658},
issn = {1558-8238},
abstract = {Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors. In this report, we investigated the role of the gut microbiome using Winnie mice, a UC-like model with a missense mutation in the Muc2 gene. Upon rederivation from a conventional (CONV) to a specific-pathogen-free (SPF) facility, Winnie mice developed severe colitis and, notably, spontaneous CAC that progressively worsened over time. In contrast, CONV Winnie showed only mild colitis but no tumorigenesis. By comparison, when rederived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis and colon tumors, indicating an essential role for the gut microbiome in the development of CAC in these mice. Using shotgun metagenomics, metabolomics, and lipidomics, we identified a distinct pro-inflammatory microbial and metabolic signature that potentially drives the transition from colitis to CAC. Fecal microbiota transplantation (FMT), using either SPF Winnie or WT (Bl/6) donors into GF Winnie recipients, demonstrated that while colitis developed regardless of the donor, only FMT from SPF Winnie donors resulted in CAC. Our studies present a relevant model of CAC, providing strong evidence that the microbiome plays a key role in its pathogenesis, thereby challenging the concept of colon cancer as a strictly non-transmissible disease.},
}

@article {pmid41196286,
year = {2025},
author = {Ni, Z and Ye, D},
title = {The impact of gut microbiota modulation on responses to immune checkpoint inhibitors in cancer.},
journal = {Acta microbiologica et immunologica Hungarica},
volume = {},
number = {},
pages = {},
doi = {10.1556/030.2025.02719},
pmid = {41196286},
issn = {1588-2640},
abstract = {The gut microbiota has emerged as a critical determinant of antitumor immunity and a potential modulator of responses to immune checkpoint inhibitors (ICIs). Although pre-clinical and clinical studies suggest that specific bacterial taxa may influence both efficacy and immune-related adverse events (irAEs). However, the magnitude and consistency of these associations remain unclear. A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted through March 2025. Eligible studies evaluated baseline gut microbiota composition, fecal microbiota transplantation (FMT), probiotic/prebiotic interventions, or antibiotic exposure in cancer patients treated with ICIs. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for response rates and irAEs, were estimated using random-effects models. Across 38 studies involving 5,642 patients were included. Pooled analysis demonstrated that enrichment of Akkermansia muciniphila, Bifidobacterium longum and Faecalibacterium prausnitzii was significantly associated with improved OS (HR 0.62, 95% CI 0.51-0.76) and PFS (HR 0.69, 95% CI 0.55-0.83). Conversely, antibiotic exposure before or during ICI treatment was associated with worse OS (HR 1.84, 95% CI 1.45-2.34). Patients undergoing FMT from responders exhibited higher objective response rates (OR 2.91, 95% CI 1.48-5.73). Microbiota diversity indices were consistently higher in responders than in non-responders. Collectively, gut microbiota composition and its modulation significantly impact the therapeutic efficacy and toxicity profile of ICIs. These findings highlight the translational potential of microbiome-based biomarkers and interventions in optimizing immunotherapy.},
}

@article {pmid41195402,
year = {2025},
author = {Ruohan, Z and Ruting, W and Hongxi, W and Zhenjin, H and Jiale, L and Rongxin, Z and Feng, J and Yuanbo, S},
title = {Gut microbiota as a novel target for treating anxiety and depression: from mechanisms to multimodal interventions.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1664800},
pmid = {41195402},
issn = {1664-302X},
abstract = {The global prevalence of depression and anxiety continues to rise, with major depressive disorder and anxiety disorders estimated to affect approximately 3.1 and 4.8% of the world's population. Yet current pharmacological treatments demonstrate limited efficacy. This limitation has spurred extensive research into alternative treatment methods. Emerging evidence highlights a complex correlation between gut microbiota (GM) imbalance and mental health disorders. Disruptions in GM may trigger or exacerbate symptoms of anxiety and depression by interfering with communication pathways between the gut and brain. These pathways include neural signaling through the vagus nerve, hormone regulation via the hypothalamic-pituitary-adrenal (HPA) axis, immune responses involving pro-inflammatory cytokines, and metabolic processes related to short-chain fatty acids (SCFAs). Preclinical studies and initial clinical trials indicate promising results for therapeutic interventions targeting gut microbiota. Given that current evidence remains constrained by insufficient depth of understanding regarding underlying mechanisms, this review explores the intricate interactions among the gut microbiota, and brain, highlighting opportunities for advanced therapeutic approaches, focusing on probiotics, prebiotics, postbiotics, synbiotics, dietary modifications, fecal microbiota transplantation (FMT), fecal virome transplantation (FVT), and traditional Chinese medicine (TCM). It elucidates the role of gut microbiota in depression/anxiety and advances therapeutic approaches.},
}

@article {pmid41194539,
year = {2025},
author = {Rolhion, N and Sokol, H},
title = {Targeting the gut microbiome in inflammatory bowel disease: from concept to clinical reality.},
journal = {Intestinal research},
volume = {23},
number = {4},
pages = {396-404},
doi = {10.5217/ir.2025.00104},
pmid = {41194539},
issn = {1598-9100},
support = {ERC-2021-COG-101043802/ERC_/European Research Council/International ; //MSDAVENIR/ ; },
abstract = {The gut microbiota, a complex community of trillions of microorganisms inhabiting the human gastrointestinal tract, has emerged as a critical regulator of immune homeostasis and gastrointestinal health. In the context of inflammatory bowel disease (IBD), comprising primarily Crohn's disease and ulcerative colitis, disruptions to this microbial ecosystem-collectively termed dysbiosis-have been increasingly recognized as central to disease pathogenesis. Recent research has established that alterations in gut microbiota not only reflect disease states but may actively drive immune dysregulation, barrier dysfunction, and mucosal inflammation. This review synthesizes current knowledge on the role of the gut microbiota in IBD and evaluates the therapeutic landscape of microbiota-modulating strategies using selected examples. Fecal microbiota transplantation, while offering proof-of-concept validation, is hindered by standardization challenges and variable clinical outcomes. As a response, microbiome-based therapeutics have evolved toward defined live biotherapeutic products including bacterial consortia and single-strain products, postbiotics, and metabolite-centered approaches targeting specific pathways. Groundbreaking research into rationally designed synthetic microbiomes and next-generation probiotics is driving a paradigm shift in microbiota-based treatment for IBD from empirical to precision-guided interventions.},
}

@article {pmid41192778,
year = {2025},
author = {Tabata, K and Ikarashi, N and Yoshida, R and Shinozaki, Y and Kato, Y and Kon, R and Iwasaki, Y and Yokoyama, K and Saito, R and Sakai, H and Hosoe, T},
title = {High-fat diet exacerbates atopic dermatitis through alterations in the gut microbiome.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110164},
doi = {10.1016/j.jnutbio.2025.110164},
pmid = {41192778},
issn = {1873-4847},
abstract = {Atopic dermatitis (AD) is a chronic, relapsing skin disorder characterized by pruritic eczema. In addition to genetic predispositions, environmental factors such as diet are thought to contribute to the exacerbation of AD. The aim of this study was to provide scientific evidence on how environmental factors, particularly a high-fat diet (HFD), influence the pathogenesis of AD. AD was induced in NC/Nga mice fed an HFD through the application of 2,4-dinitrochlorobenzene. In the AD-HFD group, the expression levels of inflammatory markers (Tnfa, Il1b, Ptgs2, and Nos2) and AD-related factors (Il4, Ccl17, and Tslp) in the skin were significantly elevated compared with those in the AD group (mice fed a normal diet). Alteration of gut microbiota was observed in the AD-HFD group, characterized by a reduction in the abundances of Bacteroides acidifaciens and Parabacteroides distasonis, bacteria involved in short-chain fatty acid (SCFA) production. Moreover, the levels of acetate, propionate, and butyrate in the cecal contents were significantly decreased in the AD-HFD group. Fecal microbiota transplantation experiments revealed that alterations in the gut microbiota were associated with the exacerbation of AD symptoms. Furthermore, the administration of acetate alleviated the increase in the expression of skin inflammation markers and AD-related factors and the overall exacerbation of AD-like symptoms induced by the HFD. HFD intake exacerbates AD-like symptoms, and this exacerbation is linked to alteration of gut microbiota and a decrease in SCFA levels. These results suggest that acetate and acetate-producing bacteria may serve as potential tools for the prevention and treatment of AD.},
}

@article {pmid41192727,
year = {2025},
author = {Lai, J and Yang, B and Ju, P and Sun, Y and Sun, X and Cheng, W and Chen, J},
title = {Gut microbiota from adolescents with social anxiety disorder is associated with behavioral alterations and metabolic changes in the medial prefrontal cortex.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {120597},
doi = {10.1016/j.jad.2025.120597},
pmid = {41192727},
issn = {1573-2517},
abstract = {BACKGROUND: Social anxiety disorder (SAD) is a prevalent and burdensome neuropsychiatric disorder characterised by pronounced and persistent fear and anxiety in social situations. While evidence links gut microbiota to neuropsychiatric disorders, its role in SAD remains poorly understood.

AIM: In this study, we aimed to investigate the potential involvement of gut microbiota in SAD pathophysiology through fecal microbiota transplantation.

METHOD: We collected demographic data and fecal samples from 40 first-episode, comorbidity-free, and drug-naive adolescent patients with SAD, along with 32 demographically matched healthy controls. Fecal samples underwent 16S rDNA amplicon sequencing and were pooled for transplantation into neonatal rats from postnatal day 1 through late adolescence. Recipient rats were evaluated with behavioral tests, microbiota detection, and non-targeted metabolomics of the medial prefrontal cortex.

RESULT: Patients with SAD displayed alterations in gut microbiota composition. Rats colonized with SAD-associated microbiota exhibited anxiety-like behaviors and reduced social novelty preference, alongside microbial profiles partially overlapping with those of patients. These behavioral changes were correlated with microbiota differences, and distinct metabolic alterations were detected in the medial prefrontal cortex of SAD-colonized rats.

CONCLUSION: Gut microbiota from adolescents with SAD is associated with behavioral and metabolic alterations in a rodent model, suggesting a potential role of the gut-brain axis in SAD. Further studies are warranted to establish causality and elucidate underlying mechanisms.},
}

@article {pmid41191115,
year = {2025},
author = {Habeeb, TAAM and Hussain, A and Bueno-Lledó, J and Giménez, ME and Aiolfi, A and Chiaretti, M and Kryvoruchko, IA and Manangi, MN and Elias, AA and Adam, AAM and Gadallah, MA and Ahmed, SMA and Khyrallh, A and Alsayed, MH and Awad, ETK and Ibrahim, EA and Elshafey, MH and Labib, MF and Badawy, MHM and Teama, SRA and Seleem, A and Abo Alsaad, MI and Ali, AK and Elbelkasi, H and Abou Zaid, MA and Mohamed, BA and Alwadees, A and El-Taher, AK and Mansour, MI and Yassin, MA and Arafa, AS and Lotfy, M and Atef, B and Elnemr, M and Khairy, MM and Abdelwanis, AH and Abdelaziz, AM and Mostafa, A and Hamed, AM and Wasefy, T and Heggy, IA and Nawar, AMH},
title = {COVID-19-specific risk factor for early post-appendectomy complications (EPAC) in older patients: a retrospective study.},
journal = {Techniques in coloproctology},
volume = {29},
number = {1},
pages = {188},
pmid = {41191115},
issn = {1128-045X},
mesh = {Humans ; Retrospective Studies ; *COVID-19/complications/epidemiology/diagnosis ; *Appendectomy/adverse effects ; Male ; Female ; Risk Factors ; Aged ; *Postoperative Complications/epidemiology/etiology ; Middle Aged ; Incidence ; *Appendicitis/surgery ; SARS-CoV-2 ; Age Factors ; Surgical Wound Infection/epidemiology ; Aged, 80 and over ; },
abstract = {BACKGROUND: The incidence of acute appendicitis in older patients significantly varies from that in younger adults. The coronavirus disease 2019 (COVID-19) pandemic has increased the risk of early post-appendectomy complications (EPAC). This study aimed to investigate the incidence and risk factors associated with EPAC in older patients after appendectomy and to define active COVID-19 infection during surgery as an associated risk factor for EPAC.

METHODS: We conducted a retrospective multicenter analysis of older patients aged ≥ 60 years who underwent appendectomy between April 2020 and December 2024. Logistic regression identified the risk factors associated with EPAC.

RESULTS: A total of 585 patients aged ≥ 60 years were divided into the EPAC (n = 32) and no EPAC (n = 553) groups. The incidences of EPAC was 5.5% (32/585), including superficial incisional surgical site infections (SSI) (9/32, 28.1%), deep incisional SSI (2/32, 6.3%), organ/space infection (2/32, 6.3%), intra-abdominal abscess (9/32, 28.1%), ileus (2/32, 6.3%), pneumonia (3/32, 9.4%), acute myocardial infraction (MI) (2/32, 6.3%), fecal fistula (2/32, 6.3%), and acute adhesive intestinal obstruction (1/32, 3.1%). Multivariable analysis identified that active COVID-19 infection during surgery (odds ratio (OR) = 25.9; 95% confidence interval (CI) 4.8-139.1; p < 0.001), American Society of Anesthesiologists (ASA) score ≥ II (OR = 4.5; 95% CI 1.2-17.07; p = 0.02), open approach (OR = 30.6; 95% CI 8.1-115.3; p < 0.001), and high-grade appendicitis ≥ IV (OR = 63.06; 95% CI 7.5-526.4; p < 0.001) were significant associated risk factors for EPAC.

CONCLUSIONS: The incidence of EPAC in older patients after appendectomy is 5.5%. Active COVID-19 infection during surgery is strongly associated with an increased risk of EPAC. COVID-19 should be considered in perioperative risk assessment of EPAC.

TRIAL REGISTRATION: This study was registered as a clinical trial (NCT06787573). Retrospectively registered.},
}

Humans
Retrospective Studies
*COVID-19/complications/epidemiology/diagnosis
*Appendectomy/adverse effects
Male
Female
Risk Factors
Aged
*Postoperative Complications/epidemiology/etiology
Middle Aged
Incidence
*Appendicitis/surgery
SARS-CoV-2
Age Factors
Surgical Wound Infection/epidemiology
Aged, 80 and over

@article {pmid41190061,
year = {2025},
author = {Ma, C and Wang, J and Song, X and Wang, X and Zong, S},
title = {Molecular mechanisms and clinical applications of gut microbiota-derived bioactive compounds in metabolic dysfunction-associated fatty liver disease.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1682755},
pmid = {41190061},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Probiotics ; Dysbiosis/metabolism ; Fecal Microbiota Transplantation ; Prebiotics ; *Non-alcoholic Fatty Liver Disease/metabolism/therapy/microbiology ; Lipid Metabolism ; Bile Acids and Salts/metabolism ; },
abstract = {Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a leading cause of chronic liver disease worldwide. Its pathogenesis is closely associated with gut microbiota dysbiosis and metabolic disturbances. In recent years, numerous studies have demonstrated that bioactive compounds produced by gut microbial metabolism-such as short-chain fatty acids, secondary bile acids, tryptophan derivatives, and bacterial extracellular vesicles-play critical roles in the development and progression of MAFLD by modulating hepatic lipid metabolism, inflammatory responses, and epigenetic regulation. The characteristic expression patterns of these gut microbiota-derived bioactive compounds provide novel options for differential diagnosis of the disease. Moreover, elucidation of the underlying pathological mechanisms has paved novel avenues for MAFLD treatment. Strategies including dietary interventions, prebiotics, probiotics, and other microbiota-targeted therapies are considered potential approaches to modulate MAFLD progression. This review systematically summarizes the molecular mechanisms underlying the development of MAFLD influenced by gut microbiota-derived bioactive compounds. It also explores the feasibility of utilizing specific gut microbial metabolite profiles for MAFLD diagnosis and highlights potential therapeutic strategies targeting microbiota-host metabolic interactions, including the use of engineered bacteria to produce specific metabolites, probiotic/prebiotic interventions, and the clinical prospects of fecal microbiota transplantation.},
}

Humans
*Gastrointestinal Microbiome
Animals
Probiotics
Dysbiosis/metabolism
Fecal Microbiota Transplantation
Prebiotics
*Non-alcoholic Fatty Liver Disease/metabolism/therapy/microbiology
Lipid Metabolism
Bile Acids and Salts/metabolism

@article {pmid41189901,
year = {2025},
author = {Bautista, J and Maldonado-Noboa, I and Maldonado-Guerrero, D and Reinoso-Quinga, L and López-Cortés, A},
title = {Microbiome influence in gastric cancer progression and therapeutic strategies.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1681824},
pmid = {41189901},
issn = {2296-858X},
abstract = {Gastric cancer (GC) remains a major global health burden, ranking as the fifth most commonly diagnosed malignancy and the fourth leading cause of cancer-related death worldwide. While Helicobacter pylori is established as the primary microbial risk factor, emerging evidence underscores the broader oncogenic potential of gastric microbiome dysbiosis. This review synthesizes recent advances in understanding how microbial communities, both within the stomach and along the gut-stomach axis, contribute to gastric carcinogenesis. We explore how alterations in microbial diversity, virulence, and metabolic output disrupt mucosal homeostasis, drive chronic inflammation, and reshape local immune surveillance. Special attention is given to the molecular mechanisms by which H. pylori virulence factors cytotoxin-associated gene A (CagA) and VacA, vacuolating cytotoxin, induce epithelial transformation, immune evasion, and epigenetic reprogramming. We also highlight the oncogenic roles of non-H. pylori taxa such as Fusobacterium nucleatum, Streptococcus anginosus, and Lactobacillus fermentum, which synergize with host and environmental factors to sustain tumor-promoting microenvironments. Multi-omics studies reveal microbial signatures predictive of disease progression, therapeutic response, and prognosis, laying the foundation for microbiome-informed precision oncology. Furthermore, we examine how microbiota-targeted interventions, probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, can enhance chemotherapy and immunotherapy efficacy while mitigating treatment-related toxicity. Lastly, we discuss the implications of early H. pylori eradication, the impact of antibiotic resistance, and the need for global surveillance strategies.},
}

@article {pmid41189008,
year = {2025},
author = {Cho, HW and Byeon, HW and Park, SO and Uyangaa, E and Choi, JY and Kim, K and Eo, SK},
title = {The gut microbiota limits systemic inflammation during neurotrophic viral CNS infection by priming tonic type I interferon signaling.},
journal = {Journal of neuroinflammation},
volume = {22},
number = {1},
pages = {259},
pmid = {41189008},
issn = {1742-2094},
support = {RS-2025-00513722//National Research Foundation of Korea/ ; RS-2021-NF000550//Korea Basic Science Institute/ ; HI22C0591//Korea Health Industry Development Institute/Republic of Korea ; },
mesh = {Animals ; *Gastrointestinal Microbiome/physiology/immunology/drug effects ; *Interferon Type I/metabolism/immunology ; Mice ; Mice, Inbred C57BL ; *Signal Transduction/physiology ; Fecal Microbiota Transplantation ; Inflammation/microbiology/immunology ; Male ; Encephalitis Virus, Japanese ; *Encephalitis, Japanese/immunology ; Neuroinflammatory Diseases ; },
abstract = {Neurotropic viruses, such as Japanese encephalitis virus (JEV), trigger central nervous system (CNS) inflammation primarily through disruption of the blood-brain barrier (BBB) and infiltration of peripheral immune cells. Although the gut microbiota is known to regulate diverse immunopathological processes, its contribution to CNS neuroinflammation and systemic immune responses during neurotropic viral infection remains poorly understood. Here, we show that depletion of gut microbiota by antibiotic cocktail treatment markedly increases susceptibility to CNS neuroinflammation following JEV infection. Loss of microbiota promoted viral dissemination into extraneural tissues, aggravated systemic inflammation and organ damage, and impaired tonic type I interferon (IFN-I) responses and hematopoietic differentiation during disease progression. Remarkably, fecal microbiota transplantation (FMT) restored resistance to CNS neuroinflammation, highlighting the protective role of the microbiota. Moreover, ampicillin-mediated depletion of specific gram-positive bacteria-including Bifidobacterium, Faecalibaculum, Ligilactobacillus, and Turicibacter-was associated with enhanced viral spread, systemic inflammation, and organ injury, accompanied by distinct shifts in fecal metabolites. Collectively, these findings demonstrate that gut microbiota-driven tonic IFN-I responses limit viral dissemination in extraneural tissues, thereby attenuating systemic inflammation and protecting against CNS neuroinflammation, particularly viral encephalitis.},
}

Animals
*Gastrointestinal Microbiome/physiology/immunology/drug effects
*Interferon Type I/metabolism/immunology
Mice
Mice, Inbred C57BL
*Signal Transduction/physiology
Fecal Microbiota Transplantation
Inflammation/microbiology/immunology
Male
Encephalitis Virus, Japanese
*Encephalitis, Japanese/immunology
Neuroinflammatory Diseases

@article {pmid41181931,
year = {2025},
author = {Khoruts, A},
title = {The challenges and opportunities in the expanding horizons of microbiota transplant therapies.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2559032},
pmid = {41181931},
issn = {1949-0984},
}

@article {pmid41188912,
year = {2025},
author = {Li, X and Hou, M and Lyu, J and Min, X and Han, X and Wang, X and Liu, Z and Leng, Y},
title = {Gut microbiota-derived arginine metabolism mitigates intestinal ischemia-reperfusion injury.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1215},
pmid = {41188912},
issn = {1479-5876},
support = {82260381//Natural Science Foundation of china/ ; },
}

@article {pmid41187620,
year = {2025},
author = {Tian, J and Cheng, J and Yang, H and Niu, Z and Zhao, L and Guan, L and Liu, N and Rong, S and Wang, C and Shi, D and Zheng, H and Cao, N and Li, R and Zhang, Y and Ren, C and Zhang, Z},
title = {Unveiling the gut-vascular connection: Gut microbiota regulates cardiovascular toxicity induced by combined exposure to PM2.5 and high-fat diet via butyric acid/NLRP3 pathway.},
journal = {Journal of hazardous materials},
volume = {499},
number = {},
pages = {140334},
doi = {10.1016/j.jhazmat.2025.140334},
pmid = {41187620},
issn = {1873-3336},
abstract = {Environmental particulate matter and dietary factors have been found to induce gut microbiota dysbiosis and exert an impact on cardiovascular toxicity. However, the underlying biological connections among them remain unclear. Our results indicated co-exposure to PM2.5 and high-fat diet (HFD) notably elevated blood pressure and blood lipid in mice and serum nitric oxide and endothelin-1 were abnormal. Meanwhile, vascular diameter and end-diastolic velocity (EDV) decreased, while resistance index (RI) increased. There was a synergistic effect of co-exposure on EDV and RI. Furthermore, significant damage to colon was observed. 16S rDNA sequencing of fecal microbiota indicated PM2.5 and HFD led to gut microbiota dysbiosis. Desulfovibrio was positively correlated with blood pressure, while Parabacteroides was negatively correlated. Fecal microbiota transplantation from donor mice exposed to hazardous substances successfully exacerbated cardiovascular toxicity in recipient mice. Further analysis of short chain fatty acids using metabolomics showed exposure to PM2.5 and HFD decreased serum butyric acid. Supplementation with sodium butyrate (SB) successfully alleviated the damage to cardiovascular system. Both in vivo and vitro experiments demonstrated SB supplementation significantly inhibited NLRP3 inflammasome. These findings indicate that modulating gut microbiota and its metabolite butyric acid may prevent the adverse cardiovascular effects of environmental PM2.5 exposure and HFD.},
}

@article {pmid41186720,
year = {2025},
author = {Aijaz, M and Ahmad, M and Ahmad, S and Afzal, M and Kothiyal, P},
title = {The gut-brain axis: role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41186720},
issn = {1432-1912},
abstract = {The gut-brain axis is a highly complex, bidirectional communication link between the gut and the central nervous system (CNS), mainly through neural, endocrine, immunological, and metabolic pathways. This review outlines the growing contribution of gut microbiota in the remediation of neurological health and also emphasizes the controlling role of gut microbiota on the synthesis of neurotransmitters. Emerging evidence indicates that dysbiosis of the gut is related to a variety of neurodegenerative and neuropsychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), autism spectrum disorders (ASD), depression, and glioblastoma. Mechanistic understandings show that gut microbes critically contribute to neuroimmune and blood-brain barrier (BBB) signaling. The peripheral association of gut microflora, networked with inflammasome activation, nuclear factor kappa B (NF-κB), and type-I IFN pathways highlights their role in CNS inflammation. Microbiota-targeted interventions with probiotics, prebiotics, synbiotics, antibiotics, dietary modifications, and fecal microbiota transplantation are examined for their therapeutic potential. These strategies appear to be promising to reinstate microbial balance, enhance neuroplastic responses, and ameliorate the disease symptoms. The review highlights personalized microbiome-based algorithms, underpinned by integrated multi-omics technologies and machine-learning-driven diagnostics. Future research should address underlying microbial mechanisms and perform large, randomized controlled trials in order to establish microbiota-based therapies for neurological disorders.},
}

@article {pmid41185751,
year = {2025},
author = {Huang, Y and Zhang, Z and Xue, L and Zhang, X and He, C},
title = {Advances in Nanomedicine-Mediated Modulation of the Microbiome for Cancer Therapy.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {13079-13096},
pmid = {41185751},
issn = {1178-2013},
mesh = {Humans ; *Neoplasms/therapy/microbiology/drug therapy ; *Nanomedicine/methods ; Tumor Microenvironment/drug effects ; Animals ; Probiotics/therapeutic use/administration & dosage ; Fecal Microbiota Transplantation/methods ; *Microbiota/drug effects ; Liposomes/chemistry ; Drug Delivery Systems ; Antineoplastic Agents/administration & dosage ; Gastrointestinal Microbiome/drug effects ; },
abstract = {The microbiome is closely related to the development of cancer, and it is feasible to modulate the microbiome for cancer therapy. Strategies based on the modulation of the microbiome, such as probiotic therapy and fecal microbiota transplantation (FMT), have achieved certain results in cancer therapy. However, poor targeting and low survival rate of the microbiome limited their further application in cancer therapy. Nanomaterials such as liposomes and micelles are widely used as carriers for drug delivery due to their good biocompatibility and stability. The latest evidence indicates that some nanomedicines can reverse cancer-promoting effects (such as promoting cell proliferation and accelerating tissue inflammation) by eliminating cancer-related microbiota, or increase the proportion of beneficial bacteria, which further enhance the production of beneficial metabolites, facilitate immune cell infiltration, and reshape the tumor microenvironment (TME), thereby inhibit tumor growth. Thus, it is promising to enhance the efficacy of cancer therapy by regulating microbiota through nanomedicines. This review highlights recent advances in the integration of nanomedicine and microbiota modulation for cancer treatment, aiming to provide insights into the design of innovative therapeutic strategies and broaden treatment options for cancer patients.},
}

Humans
*Neoplasms/therapy/microbiology/drug therapy
*Nanomedicine/methods
Tumor Microenvironment/drug effects
Animals
Probiotics/therapeutic use/administration & dosage
Fecal Microbiota Transplantation/methods
*Microbiota/drug effects
Liposomes/chemistry
Drug Delivery Systems
Antineoplastic Agents/administration & dosage
Gastrointestinal Microbiome/drug effects

@article {pmid41184709,
year = {2025},
author = {Kiecka, A and Szczepanik, M},
title = {Dietary modulation of the gut microbiome as a supportive strategy in the treatment of amyotrophic lateral sclerosis - a narrative review.},
journal = {Pharmacological reports : PR},
volume = {},
number = {},
pages = {},
pmid = {41184709},
issn = {2299-5684},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.},
}

@article {pmid41183735,
year = {2025},
author = {He, J and Lin, Z and Lin, X and Wang, C and Cao, M and Xia, R and Hong, W},
title = {Targeted fecal microbiota transplantation ameliorates autism-like behaviors via gut-brain axis and excitatory/inhibitory balance restoration in a propionic acid mouse model.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106162},
doi = {10.1016/j.bbi.2025.106162},
pmid = {41183735},
issn = {1090-2139},
abstract = {Autism spectrum disorder (ASD) is characterized by social interaction deficits, repetitive behaviors, and restricted interests. Emerging evidence suggests a role for the gut microbiota in ASD pathophysiology, with fecal microbiota transplantation (FMT) emerging as a potential therapeutic strategy. This study investigated the effects of targeted FMT using processed fecal suspensions from rigorously screened healthy human donors, selected by 16S rRNA sequencing for high Lactobacillus abundance, on a propionic acid (PPA)-induced ASD mouse model. PPA-exposed mice exhibited ASD-like behaviors, including anxiety, repetitive grooming, and social interaction deficits, along with alterations in gut microbiota composition, SCFA levels, and neurotransmitter profiles. Donor selection based on 16S rRNA gene sequencing revealed that FMT from donors with high Lactobacillus abundance was more effective in improving social interaction deficits compared to donors with lower Lactobacillus levels. Targeted FMT intervention restored gut microbiota diversity and enriched beneficial taxa, such as Lactobacillus, Roseburia, and Blautia. Furthermore, targeted FMT reduced PPA levels in both feces and the prefrontal cortex (PFC), and normalized the Glu/GABA ratio in the PFC, suggesting a restoration of E/I balance. Electrophysiological recordings confirmed that FMT corrected the E/I imbalance in PFC pyramidal neurons by reducing sEPSC frequency and increasing sIPSC frequency. These findings demonstrate that FMT can ameliorate ASD-like behaviors in a PPA-induced mouse model by modulating gut microbiota and restoring E/I balance in the brain. Our study provides foundational evidence for the potential of targeted FMT as a therapeutic strategy for ASD, highlighting the importance of donor selection based on gut microbiota composition.},
}

@article {pmid41181478,
year = {2025},
author = {Singhal, R and Ghadvaje, G and Karra, N and Gadde, ST and Chandra, P and Voruganti, BKT and Doddareddy, NP and Iftikhar, S and Patel, T},
title = {A narrative review on fecal microbiota transplantation routes in ulcerative colitis: identifying the optimal approach across key parameters.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {10},
pages = {6599-6611},
pmid = {41181478},
issn = {2049-0801},
abstract = {Fecal microbiota transplantation (FMT) has gained increasing attention as a novel therapeutic approach for treating ulcerative colitis (UC), a chronic inflammatory bowel disease that causes an imbalance in the gut microbiota. Although FMT has demonstrated the potential to induce remission in UC patients, the most effective route of administration remains an area of active investigation. This narrative review provides a comprehensive comparison of different FMT delivery methods, such as oral capsules, enemas, colonoscopy, and nasogastric or nasoenteric tubes, across a range of clinically relevant parameters, including efficacy, safety, patient satisfaction, microbiota changes, pretreatment protocols, and cost-effectiveness. Furthermore, we examined how post-FMT dietary interventions may influence microbial engraftment and improve the long-term outcomes in patients with UC. In addition to assessing these practical and clinical factors, this review highlights the importance of patient-centered considerations, such as the tolerability and convenience of each administration route. The integration of these findings can provide valuable insights into how different FMT routes affect disease outcomes and guide clinicians in optimizing the treatment for individual patients. By synthesizing current evidence on these key variables, we aimed to identify the most effective and feasible FMT approach for UC. Establishing standardized protocols for FMT administration, informed by this analysis, will be crucial for ensuring consistency in clinical practice, improving patient outcomes, and minimizing adverse events. The insights from this review will help pave the way for more targeted and individualized FMT strategies, ultimately enhancing the therapeutic landscape of UC management.},
}

@article {pmid41181343,
year = {2025},
author = {Jeyaraman, N and Jeyaraman, M and Dhanabal, P and Ramasubramanian, S and Ambrosio, L and Vadalà, G and Muthu, S},
title = {Implications of the gut microbiome in spinal cord injuries.},
journal = {Frontiers in surgery},
volume = {12},
number = {},
pages = {1668225},
pmid = {41181343},
issn = {2296-875X},
abstract = {Spinal cord injuries (SCIs) present complex challenges in medical treatment and rehabilitation, profoundly affecting the patient's physiological and neurological status. Emerging research on the gut microbiome has unveiled its potential role in influencing SCI outcomes and recovery. The gut microbiome undergoes significant changes following SCIs, which influence systemic inflammation and increase susceptibility to secondary complications, such as infections and chronic pain. These effects are linked to altered permeability, immune system dysregulation, and activation of the gut-brain axis, which represent promising therapeutic targets for the treatment of these conditions. Insights into the mechanisms underlying these effects were explored, highlighting the roles of microbial-derived metabolites like short-chain fatty acids, which have been shown to possess anti-inflammatory properties and support neuroprotective responses. The implications of these findings are significant, suggesting that interventions aimed at modulating the gut microbiome, such as the use of probiotics, prebiotics, and faecal microbiota transplantation, could complement existing SCI treatments and support recovery processes. This review aims to synthesise current knowledge on the interplay between the gut microbiome and SCIs, exploring how this relationship can influence immune modulation, inflammation, and neuroplasticity, thereby affecting recovery trajectories and the necessity for interdisciplinary research approaches that integrate neurology, microbiology, and nutrition to develop holistic, effective treatment strategies for SCI patients.},
}

@article {pmid41180995,
year = {2025},
author = {Anis, MA and Shahid, Y and Majeed, AA and Abid, S},
title = {Microbiome and gut-liver interactions: From mechanisms to therapies.},
journal = {World journal of gastroenterology},
volume = {31},
number = {40},
pages = {111409},
pmid = {41180995},
issn = {2219-2840},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology/drug effects ; *Dysbiosis/therapy/microbiology/immunology ; *Liver/microbiology/immunology/metabolism/pathology ; Probiotics/therapeutic use ; *Liver Diseases/microbiology/therapy/immunology ; Fecal Microbiota Transplantation ; Bile Acids and Salts/metabolism ; Anti-Bacterial Agents/therapeutic use ; Precision Medicine/methods ; Animals ; Host Microbial Interactions/immunology ; },
abstract = {The gut-liver axis represents a bidirectional and dynamic communication system between the gastrointestinal tract and liver, critically modulated by gut microbiota, bile acids, immune responses, and metabolic pathways. Disruption of this finely tuned axis contributes to the pathogenesis of several liver diseases, including alcohol-associated hepatitis, metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatic encephalopathy, and cholangiopathies like primary biliary cholangitis and primary sclerosing cholangitis. Dysbiosis, marked by reduced microbial diversity and dominance of pathogenic species, alters bile acid metabolism, increases gut permeability, and fuels hepatic inflammation. In cholangiopathies, the gut microbiome modulates immune dysregulation and fibrosis through complex microbial-host interactions. Emerging therapies targeting the microbiota, such as fecal microbiota transplantation, antibiotics (e.g., rifaximin, vancomycin), bile acid modulators, and probiotics, show promise in restoring microbial equilibrium, improving liver biochemistry, and reducing disease progression. Precision medicine strategies integrating genomics, metabolomics, and microbiomics offer a tailored approach for therapy and prognosis. This review highlights the central role of the gut-liver axis in liver diseases and the potential of microbiome-based interventions to shift management from symptomatic relief toward disease modification and personalized hepatology, underscoring a new frontier in liver disease therapeutics.},
}

Humans
*Gastrointestinal Microbiome/immunology/physiology/drug effects
*Dysbiosis/therapy/microbiology/immunology
*Liver/microbiology/immunology/metabolism/pathology
Probiotics/therapeutic use
*Liver Diseases/microbiology/therapy/immunology
Fecal Microbiota Transplantation
Bile Acids and Salts/metabolism
Anti-Bacterial Agents/therapeutic use
Precision Medicine/methods
Animals
Host Microbial Interactions/immunology

@article {pmid41179483,
year = {2025},
author = {Fanous, N and Talley, NJ and Chaemsupaphan, T and Lee, E and Rayamajhee, B and Baradaran Ghavami, S and Kazemifard, N and Asadzadeh Aghdaei, H and Chuang, E and Leong, RW},
title = {Microbiota-targeted strategies in IBD: therapeutic promise of 2'-fucosyllactose and beyond.},
journal = {Therapeutic advances in gastroenterology},
volume = {18},
number = {},
pages = {17562848251386319},
pmid = {41179483},
issn = {1756-283X},
abstract = {Inflammatory bowel diseases (IBD) are chronic and recurrent conditions of the gastrointestinal tract. IBD is often challenging to manage due to the complex etiology and involvement of multiple dysregulated immune pathways. Current treatments, including biologics and immunosuppressants, are associated with significant risks and side effects, highlighting the need for safer alternatives. Human milk oligosaccharides (HMOs), a group of bioactive carbohydrates found in human breast milk, play a crucial role in shaping the infant gut microbiome, modulating microbial metabolism and immune responses, and reducing inflammation. Notably, HMOs have no nutritional value for the infant and travel undigested through the upper gastrointestinal tract, serving as selective substrates for beneficial gut bacteria and supporting intestinal epithelial health. Among these, 2'-fucosyllactose (2'-FL) is the most abundant and well-studied HMO, functioning as a trisaccharide prebiotic. Emerging evidence suggests that the benefits of HMOs extend beyond infancy, with potential therapeutic applications in modulating immune responses, promoting epithelial health, and reducing inflammation in IBD. This review summarizes current research on the role of 2'-FL in inflammation and colitis, exploring its potential role in treating IBD.},
}

@article {pmid41178925,
year = {2025},
author = {Pacheco-Barcia, V and Mariño-Mendez, A and Hernandez-Jimenez, E and Jimenez-Fonseca, P and Muñoz Martín, AJ and Custodio-Cabello, S and Palka-Kotlowska, M and Gonzalez-Diaz, I and Cabezon-Gutierrez, L},
title = {Gut microbiome and nutritional strategies in gastrointestinal cancers: Clinical implications and therapeutic perspectives.},
journal = {World journal of clinical oncology},
volume = {16},
number = {10},
pages = {107877},
pmid = {41178925},
issn = {2218-4333},
abstract = {Gastrointestinal malignancies, particularly pancreatobiliary and gastroesophageal cancers, are associated with poor prognosis due to their frequent late-stage diagnosis. Many of these tumors contribute to anorexia-cachexia syndrome and malnutrition, further exacerbating disease progression. Inflammation plays a crucial role in tumor proliferation, and growing evidence suggests that gut microbiome significantly influence inflammatory responses and clinical outcomes in these patients. Additionally, the gut microbiome contributes to carcinogenesis through multiple mechanisms, including DNA damage, activation of oncogenic pathways, and modulation of immune responses. The emerging field of nutritional interventions highlight the microbiome's impact on anticancer drug responses, affecting both chemotherapy and molecular-targeted treatments. Given its pivotal role, microbiome modulation through probiotics, fecal microbiome transplantation, and antibiotics represents a promising approach for cancer prevention and treatment. In this review, we explore the intricate interplay between gut microbiome, inflammation, and nutritional status in gastrointestinal cancers, emphasizing potential therapeutic strategies to improve patient outcomes.},
}

@article {pmid41177416,
year = {2025},
author = {Bashir, B and Gulati, M and Vishwas, S and Hussain, MS and Gupta, G and Kumar, P and Negi, P and Mittal, N and Dua, K and Singh, SK},
title = {Bridging the gap in the management of Alzheimer's disease using fecal microbiota transplantation.},
journal = {Molecular and cellular neurosciences},
volume = {},
number = {},
pages = {104052},
doi = {10.1016/j.mcn.2025.104052},
pmid = {41177416},
issn = {1095-9327},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disease that greatly impairs the health status of human beings and creates significant burdens on individuals, families, and society. AD is characterized by the buildup of pathological proteins and glial cell dysregulated activity. Additional hallmark features include oxidative stress, neuroinflammation, impaired autophagy, cellular senescence, mitochondrial dysfunction, epigenetic alterations, reduced neurogenesis, increased blood-brain barrier permeability, and age-inappropriate intestinal dysbiosis. There is significant evidence that shows that microbiota in the gut affects the development and progression of AD. As a result, gut microbiota modulation has been identified as a new method of clinical management of AD, and more and more efforts have been devoted to identifying new methodologies for its prevention and treatment. This paper will discuss the role of gut microbiome in the etiopathogenesis of AD and consider the possibilities of fecal microbiota extract (FME) supplementation, commonly referred to as fecal microbiota transplantation (FMT). It is both a prophylactic and curative approach. The FMT therapy is grounded on the premise that anti-inflammatory effects, modifications of amyloid β, improved synaptic plasticity, short-chain fatty acids, and histone acetylation are the principles behind the enhancement of AD. The current review will present an overview of the linkage between FMT and AD as well. It further examines and evaluates the effects of FMT on aging-based mechanisms that support the development of AD. It also provides a broad description of the recent clinical and preclinical evidence on the application of FMT to AD.},
}

@article {pmid39882797,
year = {2025},
author = {Steinsbø, Ø and Aasprong, OG and Aabakken, L and Karlsen, LN and Grimstad, T},
title = {Fecal Calprotectin Correlates With Disease Extent but Remains a Reliable Marker of Mucosal Healing in Ulcerative Colitis.},
journal = {The American journal of gastroenterology},
volume = {120},
number = {11},
pages = {2623-2631},
pmid = {39882797},
issn = {1572-0241},
support = {//AbbVie, Tillotts Pharma/ ; },
mesh = {Humans ; *Leukocyte L1 Antigen Complex/analysis/metabolism ; *Colitis, Ulcerative/pathology/metabolism/diagnosis ; *Feces/chemistry ; Male ; Female ; *Intestinal Mucosa/pathology ; Middle Aged ; Biomarkers/analysis/metabolism ; Adult ; Severity of Illness Index ; Colonoscopy ; Aged ; },
abstract = {INTRODUCTION: Fecal calprotectin (FC) is a marker of mucosal inflammatory activity in ulcerative colitis (UC). FC levels may also be influenced by the extent of disease. We aimed to examine the relationships between FC, mucosal activity, and disease extent and to assess how disease extent affects the diagnostic accuracy of FC.

METHODS: We conducted a single-center observational study of patients with UC. Mucosal inflammatory activity was rated by the Mayo Endoscopic Score (MES) and Nancy Histological Index (NHI). The endoscopic and histological extents of disease were categorized by the Montreal classification and colorectal distribution of histologically active inflammation (NHI ≥ 2), respectively. FC was measured by EliA Calprotectin Enzyme fluoroimmunoassay (Phadia).

RESULTS: A total of 518 visits by 254 patients were analyzed. In endoscopically active UC (MES ≥ 2), FC levels were significantly lower in proctitis (440 [interquartile range (IQR) 175-1,350] mg/kg) as compared with left-sided colitis (840 [IQR 298-2,011] mg/kg, P = 0.048) or pancolitis (1,690 [IQR 723-2,582] mg/kg, P = 0.00005). In MES ≤1, FC levels were significantly higher in pancolitis (85 [IQR 43-350] mg/kg) as compared with proctitis (24 [IQR 15-116] mg/kg, P = 0.00032) or left-sided colitis (40 [IQR 15-160] mg/kg, P = 0.012). However, FC remained a reliable marker of mucosal healing across all disease extents, with area under the receiver-operating characteristic curve ranging from 0.878 to 0.915, and no significant differences between the extent categories (DeLong test, P ≥ 0.2919).

DISCUSSION: FC showed a significant association with disease extent yet remained a reliable surrogate marker for mucosal healing across all disease extents.},
}

Humans
*Leukocyte L1 Antigen Complex/analysis/metabolism
*Colitis, Ulcerative/pathology/metabolism/diagnosis
*Feces/chemistry
Male
Female
*Intestinal Mucosa/pathology
Middle Aged
Biomarkers/analysis/metabolism
Adult
Severity of Illness Index
Colonoscopy
Aged

@article {pmid41177025,
year = {2025},
author = {Singh, DP and Bijalwan, V and Poonam, J and Lal, R and Palkhade, R and Viramgami, A and Vidhani, H and Kumar, A and Bishnoi, M and Das, S},
title = {Bisphenol-A at an environmentally plausible dose caused gut microbiota-led impaired cognitive performances in adult mice.},
journal = {Journal of hazardous materials},
volume = {499},
number = {},
pages = {140254},
doi = {10.1016/j.jhazmat.2025.140254},
pmid = {41177025},
issn = {1873-3336},
abstract = {Omnipresent Bisphenol-A (BPA) exposure is linked to neurobehavioral deficits and gut dysbiosis. However, studies assessed its impact on cognitive performance at environmentally unrealistic doses. Nevertheless, the exact mechanism underlying the neurobehavioral phenotype, linking the role of gut microbiota is poorly understood. Here, we evaluated the effects of environmentally plausible dose of BPA-exposure on cognitive task performances with the functional analysis of gut metagenome to elucidate the role of microflora-gut-brain axis in behavioural regulation. Swiss albino mice were exposed to BPA for 5 weeks assessed for working and spatial navigation task performances. qRT-PCR based gene expression, histological investigation, gut permeability, molecular and biochemical markers of neuro-inflammation, leaky gut, oxido-nitrosative stress and 16 s rRNA gene based metagenomics with functional analysis were performed. BPA exposure altered the cognitive task performances (mean difference for transfer latency in elevated plus maze 20.84 ± 5.64 sec in and -13.12 ± 3.53 in Morris' water maze), changed serotonin levels (-70.95 ± 21.43) and acetylcholinesterase activity (0.0032 ± 0.0008), enhanced ileal permeability (12.36 ± 3.56) and systemic and tissue level inflammation (increased brain LPS, TNF-a, IL-1b, IL-6 and circulating TNF-a and IL-1b), coupled with reduced SCFAs levels (acetate; 32.48 ± 8.48, and butyrate; 28.16 ± 9.86). Faecal microbial transplant cohort replicated similar behavioural, biochemical and molecular patterns, suggesting the role of gut-microbiota in the phenotype determination. Functional pathways prediction suggested altered serotonin, dopamine, SCFAs metabolism and LPS biosynthesis. BPA at a much lower but environmentally relevant dose altered the cognitive performances, which has potential linkage to gut-microbiota mediated pathways.},
}

@article {pmid41176272,
year = {2025},
author = {Gilbert, MS and Cai, Y and Minderhoud, R and Edens, MGJ and Folkerts, G and Braber, S and Gerrits, WJJ},
title = {Effects of galacto-oligosaccharides and microbiota transfer on lung health and performance of calves.},
journal = {Journal of dairy science},
volume = {},
number = {},
pages = {},
doi = {10.3168/jds.2025-27121},
pmid = {41176272},
issn = {1525-3198},
abstract = {Bovine respiratory disease is a major multifactorial health issue in calves. Our objective was to evaluate the effects of galacto-oligosaccharide supplementation, microbiota transfer, and their interaction on lung health and performance of calves. A total of 180 male Holstein-Friesian calves at 18 ± 3.6 d of age received 1 of 4 treatments according to a 2 × 2 factorial design for 8.5 wk (period 1). Calves received galacto-oligosaccharides (GOS) via the milk replacer or not (CON) and received a microbiota transfer (MT) or not (MOCK). The MT strategy consisted of a combination of an oral rumen microbiota transfer and a fecal microbiota transfer supplied orally and rectally. The MT or MOCK procedure was applied 3 times in the first week after arrival and was repeated within a week after a group antimicrobial treatment. Clinical health was scored weekly, and BW was measured every 4 wk. Bronchoalveolar lavage fluid (BALF) and blood samples were collected biweekly from a subset of calves (n = 108). After period 1, all calves received the same control milk replacer for 4 wk (period 2), during which performance and clinical health were measured. Clinical scores increased from wk 1 to 3, and BALF IL-8 concentrations increased with time in period 1. This high infection pressure resulted in a requirement of 6 group antimicrobial treatments (supplied to all calves). Supplementation with GOS increased the ADG adjusted to equal solid feed intake (+27 g/d) in period 1 and tended to increase it (+45 g/d) in period 2. Supplementation with GOS decreased clinical scores in wk 1 and 3 (in the absence of MT) but tended to increase it in wk 6. Furthermore, GOS tended to decrease rectal temperature in period 2. Cytokine concentrations in BALF and blood were not affected by GOS, but the percentage of lymphocytes in BALF was increased by GOS, accompanied by a decrease in lymphocyte and an increase in neutrophil percentage in plasma. Microbiota transfer reduced plasma white blood cell concentration, related to a relative decrease in plasma neutrophils. Microbiota transfer reduced the percentage of BALF lymphocytes, and in wk 5, it also reduced the BALF concentration of TNFα. However, MT did not affect performance. At the start of period 2, MT even increased clinical scores in the absence of GOS, resulting in a higher individual antimicrobial treatment supply to MT calves in period 2, ultimately reducing the rectal temperature of MT calves at the end of period 2. Hardly any interactions between GOS and MT occurred, suggesting the absence of an additive relation. In conclusion, GOS improved performance and even tended to increase it after GOS supplementation ended, but this was not related to lung health. Microbiota transfer affected some inflammatory parameters, pointing toward reduced systemic and respiratory inflammation, but this was not reflected in clinical health, which even decreased in the carry-over period.},
}

@article {pmid41175891,
year = {2025},
author = {Minari, TP and Pisani, LP},
title = {The Role of Gut Microbiota in Chronic Noncommunicable Diseases: An Overview of the Last Decade.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuaf200},
pmid = {41175891},
issn = {1753-4887},
abstract = {The gut microbiota has emerged as a key modulator of various health outcomes, including chronic noncommunicable diseases (NCDs). Obesity, diabetes, and hypertension represent important clinical challenges. Recent research suggests that gut dysbiosis may contribute to the pathophysiology of NCDs through metabolic and inflammatory pathways. This narrative review evaluates current scientific evidence on the role of gut microbiota in NCDs, examining its impact on blood pressure, glucose regulation, and weight control. It also explores interactions with medications, prebiotics, probiotics, fecal transplants, and lifestyle changes while identifying research gaps to advance understanding and inform innovative therapeutic strategies. An extensive review was conducted across multiple scientific databases, including PubMed, Web of Science, CrossRef, Google Scholar, and Scopus. Articles published between 2015 and 2025 were collected. A total of 115 relevant studies were identified and analyzed. The findings demonstrate consistent associations between gut dysbiosis and NCDs. Genera such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Fusicatenibacter were depleted in disease states, while Prevotella and Clostridium sensu stricto 1 were often enriched in obesity, diabetes, and hypertension. Microbial imbalances, including altered Bacillota/Bacteroidota ratios and reduced short-chain fatty acid production, were implicated in low-grade inflammation and metabolic disruption. Current findings suggest that fecal transplantation, prebiotics, postbiotics (bioactive compounds resulting from probiotic activity), and probiotics have limited effectiveness in improving gut microbiota, emphasizing the need for further human studies. Several drugs can positively or negatively alter the composition of the microbiota. Gut microbiota imbalances contribute meaningfully to the onset and progression of major NCDs. Although emerging therapies offer promise, clinical translation requires more robust, longitudinal studies integrating microbiome profiling, metabolic outcomes, and personalized strategies. Advancing microbiota-targeted approaches may help bridge current gaps in NCD prevention and management.},
}

@article {pmid41175586,
year = {2025},
author = {Shang, Z and Zhou, L and Liu, Y and Yang, X and Yao, D and Zhai, F and Liu, B and Chen, Y and Zhu, X and Liu, D and Yi, B},
title = {Tongxie Yaofang attenuates ulcerative colitis by modulating gut microbiota and IL-10RA/NF-κB-mediated macrophage polarization.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157459},
doi = {10.1016/j.phymed.2025.157459},
pmid = {41175586},
issn = {1618-095X},
abstract = {BACKGROUND: Tongxie Yaofang (TXYF), a traditional Chinese herbal formula, has shown therapeutic potential in gastrointestinal disorders. However, its mechanism in ulcerative colitis (UC) remains unclear. This study provides new insights into immune-microbiota crosstalk as a key mechanism driving the protective effects of TXYF.

METHODS: A DSS-induced colitis mouse model was used to evaluate TXYF's efficacy. Gut microbiota was profiled by 16S rRNA sequencing, while transcriptomics and network pharmacology identified core pathways. In vivo and in vitro assays examined immune regulation and epithelial barrier function. A THP-1/Caco-2 co-culture system explored IL-10RA-dependent immune-epithelial crosstalk, and fecal microbiota transplantation (FMT) tested the functional role of microbial remodeling.

RESULTS: TXYF alleviated colitis symptoms, improved colon histology, and reduced pro-inflammatory cytokines. It reshaped gut microbiota by enriching SCFA-producing beneficial taxa and suppressing pathogenic bacteria. Transcriptomic analyses identified IL-10RA/NF-κB as a novel regulatory axis, and TXYF enhanced IL-10RA expression, inhibited NF-κB activation, and promoted M2 macrophage polarization. The co-culture model revealed IL-10RA-dependent macrophage-epithelial signaling that strengthened tight junction integrity. Importantly, FMT from TXYF-treated donors yielded these therapeutic benefits, reinforcing the evidence for microbiota-driven causality.

CONCLUSION: This study is the first to identify IL-10RA/NF-κB as a key immunoregulatory pathway of TXYF, uncover IL-10RA-dependent immune-epithelial communication, and validate gut microbiota as a functional mediator through FMT. Collectively, these findings demonstrate the innovative potential of TXYF as a multi-target herbal therapy for UC.},
}

@article {pmid41175583,
year = {2025},
author = {Ning, F and Luo, S and Nong, T and Lu, L and Yin, Z and Qin, Z and Huang, M and Jin, J},
title = {Total tanshinones extract alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying intestinal flora and suppressing the LPS-TLR4 axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157458},
doi = {10.1016/j.phymed.2025.157458},
pmid = {41175583},
issn = {1618-095X},
abstract = {BACKGROUND: Total tanshinones (T-Tan) extract, a class of lipophilic abietane diterpenes isolated from Salvia miltiorrhiza Bunge, exhibits anti-inflammatory effects. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urologic disorder. Dysbiosis of gut microbiota is closely related to CP/CPPS. However, whether T-Tan extract can regulate the intestinal flora to improve CP/CPPS remains unclear.

PURPOSE: The aim of this study was to investigate the effect of T-Tan extract on CP/CPPS and elucidate the mechanisms through which T-Tan extract modulates gut microbiota to ameliorate CP/CPPS.

METHODS: The pseudo-germ-free model was established by administering antibiotics (abx) water, and the experimental autoimmune prostatitis (EAP) model was induced via subcutaneous injections of prostate protein extract emulsified with Freund's adjuvant. The 16S rDNA method was used to analyze the structure and differential species of rat intestinal flora. Chronic pelvic pain was assessed by applying von Frey filaments. Inflammatory factors were detected by ELISA, qPCR and IHC. HE staining was used to evaluate histopathology. Immune cell markers were localized using IF. The expression levels of TLR4 pathway were detected by WB, IHC and qPCR. The graphical abstract is made by Figdraw.

RESULTS: T-Tan extract and its major compound tanshinone IIA (Tan IIA) alleviated abnormal pain and reduced inflammation. Moreover, they restored intestinal flora composition, reduced LPS levels, and downregulated the TLR4 pathway. In addition, fecal microbiota transplantation (FMT) preserved the protective effects of T-Tan extract, reduced inguinal pain, attenuated inflammatory responses, and inhibited the LPS-TLR4 signaling axis. Besides, we further confirmed that the role of intestinal flora in the treatment of CP/CPPS.

CONCLUSION: T-Tan extract could alleviate CP/CPPS by modulating the intestinal flora and then inhibiting the LPS-TLR4 axis, which is helpful for developing novel, microbiota-focused therapeutic strategies to treat CP/CPPS.},
}

@article {pmid41174753,
year = {2025},
author = {Xing, Y and Liu, C and Zhang, C and Zhou, D and Hu, B and Jiang, Q and Chen, J and Lin, Z and Wang, T and Yan, H and Liu, A and Lu, W and Ben, X and Yang, K and Yuan, JX and Zhan, W and Wang, J},
title = {Antibiotic-driven and microbiota-targeted therapy for advanced management of pulmonary hypertension.},
journal = {Respiratory research},
volume = {26},
number = {1},
pages = {303},
pmid = {41174753},
issn = {1465-993X},
support = {82120108001//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Hypertension, Pulmonary/drug therapy/microbiology/physiopathology ; *Anti-Bacterial Agents/therapeutic use/pharmacology/administration & dosage ; Male ; Retrospective Studies ; Rats ; Humans ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects/physiology ; Aged ; Rats, Sprague-Dawley ; *Disease Management ; Cohort Studies ; *Microbiota/drug effects ; },
abstract = {BACKGROUND: Pulmonary hypertension (PH), particularly secondary to hypoxic lung diseases like chronic obstructive pulmonary disease (COPD), lacks effective targeted therapies. Emerging evidence suggests that microbiota imbalances contribute to PH progression, raising the possibility of microbiome-targeted interventions. This study explores the role of antibiotics in modulating microbiota and ameliorating PH.

METHODS: A retrospective cohort analysis was conducted using the Medical Information Mart for Intensive Care (MIMIC) database to assess changes in mean pulmonary artery pressure (mPAP) after antibiotic treatment. Subsequently, clinical data of 220 PH patients (including group 1, 3, and 4 PH) from single clinical center were analyzed, with 16S rRNA sequencing performed on pharyngeal and fecal samples to evaluate microbiota composition. A hypoxia-induced PH rat model was used to investigate the effects of antibiotic treatment on hemodynamics, pulmonary vascular remodeling, and gut microbiota.

RESULTS: Antibiotic use was associated with reduced mPAP in PH patients, particularly in hypoxic associated PH. Microbiota diversity decreased with antibiotic treatment, but probiotic species like Lactobacillus were enriched. In hypoxia-induced PH rats, antibiotics attenuated right ventricular systolic pressure (RVSP), reduced pulmonary vascular thickening, and preserved gut villi integrity. Lactobacillus and Anaerostipes correlated negatively with PH severity, suggesting a protective role.

CONCLUSION: Antibiotic-driven microbiota modulation may alleviate PH progression by targeting dysbiosis and reducing inflammation. These findings support further investigation into optimized antibiotic regimens as a therapeutic strategy for PH, particularly in hypoxic lung disease-associated cases.},
}

Animals
*Hypertension, Pulmonary/drug therapy/microbiology/physiopathology
*Anti-Bacterial Agents/therapeutic use/pharmacology/administration & dosage
Male
Retrospective Studies
Rats
Humans
Middle Aged
Female
*Gastrointestinal Microbiome/drug effects/physiology
Aged
Rats, Sprague-Dawley
*Disease Management
Cohort Studies
*Microbiota/drug effects

@article {pmid41172243,
year = {2025},
author = {Hovmand, KA and Nielsen, FD and Jochumsen, EA and Kjeldsen, J and Holm, DK and Nilsson, AC and Justesen, US and Kragsnaes, MS},
title = {Impact of storage conditions on live bacteria in partially processed faecal microbiota transplantation products using culturomics.},
journal = {Letters in applied microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/lambio/ovaf126},
pmid = {41172243},
issn = {1472-765X},
abstract = {Faecal microbiota transplantation (FMT) is an effective treatment for Clostridioides difficile infection, but current FMT product manufacturing protocols are time-sensitive, labour-intensive, and require specialised staff. Delays can compromise microbial viability and product quality. Efficient storage methods for partially processed FMT material could therefore improve flexibility and streamline production. Therefore, this feasibility study evaluated the impact of storage conditions on live bacteria in partially processed donations containing glycerol as a cryoprotectant. Using culturomics, we assessed the concentration and composition of live bacteria immediately after half-way processing (reference, 0 h) or after storage at 5°C (refrigerator) or -80°C (freezer) for up to 72 h. Each FMT product was initially processed from one faecal donation provided by one of four screened donors. Storage at -80°C preserved the amount and composition of live bacteria in partially processed products. In contrast, storage at 5°C led to reduced bacterial concentrations and compositional shifts, particularly affecting the abundance of Bacteroides spp. These results highlight the potential adverse effects of refrigerator storage on bacterial viability, suggesting it may not be suitable for maintaining the quality of partially processed encapsulated FMT products. Freezer storage, however, emerged as a reliable method to preserve the content of live bacteria for at least 72h.},
}

@article {pmid41171386,
year = {2025},
author = {Singh, S and Kriti, M and Sharma, P and Pal, N and Sarma, DK and Verma, V and Tiwari, RR and Kumar, M},
title = {From Gut to Reproductive Health: Exploring Microbiome Interactions and Future Interventions.},
journal = {Reproductive sciences (Thousand Oaks, Calif.)},
volume = {},
number = {},
pages = {},
pmid = {41171386},
issn = {1933-7205},
abstract = {Recent advances in microbiome research have illuminated the complex bidirectional interactions between gut health and reproductive well-being. Understanding the gut microbiome's influence on the reproductive system and vice versa reveals how both of them can affect hormone production, immune function, and ultimately overall reproductive health. Dysbiosis, an imbalance in the gut microbial community, has been linked with a range of reproductive issues, including decreased sperm count and motility, erectile dysfunction, polycystic ovary syndrome (PCOS), endometriosis, infertility, and adverse pregnancy outcomes. This review critically evaluates emerging therapeutic interventions aimed at restoring microbial balance and enhancing reproductive health, such as use of prebiotics, probiotics, bacteriophage therapy, and fecal microbiota transplantation (FMT). By exploring the intricate interplay between gut microbiota and reproductive health, this review also emphasizes the need for integrated approaches in research and clinical practice to develop effective microbiome-based therapies for better reproductive health outcomes.},
}