@article {pmid41313537,
year = {2025},
author = {Vishwakarma, RK and Gautam, P and Sahu, M and Nath, G and Yadav, BS},
title = {Gut Microbiome in Obesity: A Narrative Review of Mechanisms, Interventions, and Future Directions.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41313537},
issn = {1867-1314},
abstract = {Obesity has reached pandemic levels worldwide and is increasingly recognized as a multifactorial condition beyond excess caloric intake and sedentary lifestyle. Accumulating evidence emphasizes that the gut microbiota (GM), primarily composed of Firmicutes and Bacteroidetes, plays a crucial role in regulating energy balance, immune response, and host metabolism. Gut dysbiosis, characterized by reduced microbial diversity and altered phylum-level composition and shifts toward commonly observed higher Firmicutes-to-Bacteroidetes ratios (although this finding is inconsistent across studies), contributes to enhanced energy harvest, systemic inflammation, and metabolic dysfunction. Key mechanisms involve GM production of short-chain fatty acids (SCFAs) and modulation of hormonal signals, including leptin, ghrelin, insulin, GLP-1, and PYY, alongside interactions via the gut-brain axis. These pathways link microbial composition to appetite regulation, fat storage, and energy balance. Emerging microbiome-targeted therapies, such as probiotics, prebiotics, dietary modulation (e.g., fiber-rich diets), fecal microbiota transplantation, and bacteriophage therapy, show promise in restoring GM balance, promoting weight loss, and improving metabolic health, though results vary and require further validation. Despite advances in metagenomics and metabolomics, gaps persist in establishing causality and long-term efficacy. The integration of GM data with host genetics, diet, and environmental factors through systems biology has the potential to facilitate personalized management of obesity. This review synthesizes the GM's role in obesity pathogenesis and hormonal regulation, highlighting therapeutic potential and research directions for microbiota-based prevention and treatment.},
}

@article {pmid41312988,
year = {2025},
author = {Schluter, J and Jogia, W and Matheis, F and Ebina, W and Sullivan, AP and Gordon, K and Cruz, EFdl and Victory-Hays, ME and Heinly, MJ and Diefenbach, CS and Kang, UJ and Peled, JU and Foster, KR and Levitt, A and McLaughlin, E},
title = {A retrospectively registered pilot randomized controlled trial of postbiotic administration during antibiotic treatment increases microbiome diversity and enriches health-associated taxa.},
journal = {Infection and immunity},
volume = {},
number = {},
pages = {e0039025},
doi = {10.1128/iai.00390-25},
pmid = {41312988},
issn = {1098-5522},
abstract = {Antibiotic-induced microbiome injury, defined as a reduction of ecological diversity and obligate anaerobe taxa, is associated with negative health outcomes in hospitalized patients, and healthy individuals who received antibiotics in the past are at higher risk for autoimmune diseases. Postbiotics contain mixtures of bacterial fermentation metabolites and bacterial cell wall components that have the potential to modulate microbial communities. Yet, it is unknown if a fermentation-derived postbiotic can reduce antibiotic-induced microbiome injury. Here, we present the results from a single-center, randomized placebo-controlled trial involving 32 patients who received an oral, fermentation-derived postbiotic alongside oral antibiotic and probiotic therapy for non-gastrointestinal (GI) infections. At the end of the antibiotic course, patients receiving the postbiotic (n = 16) had significantly higher fecal bacterial alpha diversity (+40%, inverse Simpson index) compared to the placebo group (n = 16), and the treatment was well-tolerated. Analysis of 157 longitudinal fecal samples revealed that this increased diversity was driven by enrichment of health-associated taxa, notably obligate anaerobic Firmicutes, particularly Lachnospiraceae. In contrast, Escherichia/Shigella species, often linked to pathogenicity and antibiotic resistance, were reduced in postbiotic-treated patients at the end of antibiotic treatment and remained lower up to 10 days later. Our findings suggest that postbiotic co-administration during antibiotic therapy may augment health-associated gut microbiome composition and mitigate antibiotic-induced microbiome injury.Trial registration ISRCTN30327931 retrospectively registered.},
}

@article {pmid41312383,
year = {2025},
author = {Miao, Z and Long, J and Huang, B and Yan, D and Wang, A},
title = {Roseburia hominis enriched by baicalin reverses the non-response to metformin via upregulating linolenic acid metabolism.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113892},
pmid = {41312383},
issn = {2589-0042},
abstract = {Metformin is the most commonly used hypoglycemic drug for patients with type 2 diabetes (T2D), but about 30% of patients show non-response potentially linked to gut microbiota imbalance. Although baicalin exhibits potent gut microbiota-modulating activity, its role in reversing metformin non-response remains unclear. Here, we recruited patients with T2D who were non-responders to metformin treatment and collected their fecal samples to construct a humanized mouse model via fecal microbial transplantation. We found that baicalin combined with metformin improved the abnormal glucose tolerance in non-response mice, in which Roseburia hominis was considerably enriched. Mechanically, baicalin combined with metformin activated the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)/carnitine palmitoyl transferase 1 (CPT1) pathway, and its enriched R. hominis promoted linolenic acid metabolism, thus reversing the non-response to metformin. Besides, the efficacy of R. hominis in reversing the non-response of metformin was dependent on phospholipase A2 (linolenic acid metabolism key enzyme). Our findings provide feasibility strategies for the metformin treatment of non-responsive patients.},
}

@article {pmid41310268,
year = {2025},
author = {Fazeli, SA and Soleimani Samarkhazan, H},
title = {Metabolic Memory Following Metabolic Bariatric Surgery: Mechanisms, Clinical Implications, and Strategies for Long-Term Success.},
journal = {Obesity surgery},
volume = {},
number = {},
pages = {},
pmid = {41310268},
issn = {1708-0428},
abstract = {Metabolic bariatric surgery (MBS) treats severe obesity, but long-term benefits are often lost to weight regain and metabolic relapse driven by persistent molecular imprints. This narrative review synthesizes recent evidence and examines epigenetic, inflammatory, mitochondrial, and microbiota mechanisms underlying metabolic memory after MBS. Key imprints include altered adipose transcriptomes (e.g., lower IGF1 and GPX3), persistent NLRP3 inflammasome activation, and gut dysbiosis with variable, individual patterns. We highlight how these mechanisms drive clinical outcomes such as type 2 diabetes recurrence and residual cardiovascular risk, with tissue-specific epigenetic retention slowing renal and cardiac recovery. We evaluate evidence-based strategies to counteract or modulate metabolic memory. These include the strategic selection of bariatric procedure, preoperative metabolic optimization, Mediterranean diets rich in polyphenols, GLP-1/GIP co-agonists, senolytics (e.g., dasatinib + quercetin), and autologous fecal microbiome transplantation. Emerging preclinical approaches like CRISPR-dCas9 epigenetic editing and exploratory strategies like vagal neuromodulation show theoretical promise in targeting obesogenic memory pathways but remain far from clinical application. The review underscores the need for longitudinal multi-omics cohorts and metabolic memory biomarkers (e.g., PPARGC1A methylation, CCL25) to enable personalized interventions. By targeting metabolic memory proactively, MBS can evolve from weight-loss procedure to a durable reset of metabolic set points. However, it is crucial to acknowledge that many proposed strategies are derived from preliminary studies with limited sample sizes and follow-up, necessitating further validation in large-scale trials.},
}

@article {pmid41077329,
year = {2025},
author = {González-Rico, C and Hernández, M and Rodríguez-Grande, J and Fernández-Luis, S and Bermúdez Rodríguez, A and González-Huerta, AJ and Llaneza Velasco, E and Vázquez López, L and García García, I and Arnaiz de Las Revillas, F and Fariñas-Álvarez, C and Calvo Montes, J and Ocampo-Sosa, A and Fernández-Martínez, M and Fariñas, MC and , },
title = {Changes in the bacterial profile and diversity of the gut microbiota in allogeneic hematopoietic stem cell transplant recipients.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {161},
number = {},
pages = {108117},
doi = {10.1016/j.ijid.2025.108117},
pmid = {41077329},
issn = {1878-3511},
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome/genetics ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation & purification ; Transplantation, Homologous ; Graft vs Host Disease/microbiology ; Feces/microbiology ; Young Adult ; Aged ; Spain ; },
abstract = {OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with significant alterations in gut microbiota (GM) composition, affecting transplant success. This study aimed to correlate these GM changes with post-transplant (post-HSCT) outcomes.

METHODS: A prospective multicentre cohort study was conducted between June 2017 and December 2021 in three Spanish hospitals. Stool samples from allo-HSCT recipients were collected before HSCT, and at 14-, 30-, 60-, and 100-days post-HSCT. Bacterial 16S rRNA gene sequences were characterized and microbial diversity assessed.

RESULTS: Analysis of 409 samples from 95 patients revealed significant longitudinal GM shifts. Alpha diversity significantly decreased at days 14 (P < 0.001), 30 (P < 0.001), and 60 (P = 0.002) compared to baseline. A distinct shift in dominant taxonomic profiles was observed, notably a significant decrease in Blautia abundance (P < 0.001). Patients with acute gastrointestinal graft-versus-host disease (GI-GVHD) (P = 0.009), bacteraemia (P = 0.014), or death (P < 0.001) exhibited significantly lower Blautia levels. LEfSe analysis identified 22 differential taxa between deceased and surviving patients; the former showed higher abundance of potential pathogens such as Enterococcus_H (P = 0.026), Enterococcus_A (P = 0.019), and Staphylococcus (P = 0.009).

CONCLUSIONS: Significant variations in the GM's taxonomic profiles and relative abundances post-HSCT, particularly the decrease in Blautia and the increase in certain pathogens, are associated with poorer clinical outcomes.},
}

Humans
*Hematopoietic Stem Cell Transplantation/adverse effects
*Gastrointestinal Microbiome/genetics
Male
Female
Middle Aged
Prospective Studies
Adult
RNA, Ribosomal, 16S/genetics
*Bacteria/classification/genetics/isolation & purification
Transplantation, Homologous
Graft vs Host Disease/microbiology
Feces/microbiology
Young Adult
Aged
Spain

@article {pmid41309372,
year = {2025},
author = {Xu, S and Su, W and Qin, Z and Xuan, Z and Wang, J and Wang, J and Tang, R and Yin, J and Liang, J and Jia, X},
title = {Er Miao San Attenuates Collagen-Induced Arthritis Mice by Regulating Gut Microbiota and Its Metabolites.},
journal = {Journal of microbiology and biotechnology},
volume = {35},
number = {},
pages = {e2507054},
doi = {10.4014/jmb.2507.07054},
pmid = {41309372},
issn = {1738-8872},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Arthritis, Experimental/drug therapy/microbiology ; Fecal Microbiota Transplantation ; Male ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/drug therapy ; Fatty Acids, Volatile/metabolism ; *Arthritis, Rheumatoid/drug therapy/microbiology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred DBA ; Butyrates/metabolism ; Bacteria/classification/genetics/metabolism/drug effects ; Disease Models, Animal ; Bacteroidetes/drug effects ; },
abstract = {Dysbiosis of the gut microbiota plays a key role in the pathogenesis of rheumatoid arthritis (RA). However, it is still unclear whether the classic prescription Er Miao San (EMS) can exert therapeutic effects on RA by regulating the gut microbiota. In this study, we investigated whether EMS alleviates collagen-induced arthritis (CIA) by modulating the gut microbiota and its metabolites. We demonstrated that EMS significantly reduced arthritis severity, paw swelling, and systemic inflammation in CIA mice. In addition, 16S rRNA sequencing analysis revealed that EMS restored gut microbiota homeostasis, as evidenced by an increased abundance of Bacteroidetes, and a decreased Bacteroidetes/Firmicutes ratio. Crucially, antibiotic depletion of the gut microbiota abolished the protective effects of EMS, whereas fecal microbiota transplantation (FMT) from EMS-treated donors replicated its anti-arthritic efficacy, confirming the indispensable role of the microbiota. Measurement of short-chain fatty acids (SCFAs) further revealed a significant increase in the microbial metabolite butyrate following EMS treatment. Subsequent supplementation with sodium butyrate mimicked the therapeutic effects of EMS, ameliorating joint inflammation and cartilage damage. Mechanistically, butyrate enhanced the expression of intestinal tight junction proteins (ZO-1 and occludin), thereby restoring intestinal barrier integrity. Collectively, our results demonstrate that EMS exerts its anti-arthritic effects by modulating the gut microbiota-butyrate-intestinal barrier axis, highlighting the critical value of microbial metabolites in RA treatment. This study provides novel insights into the mechanism of EMS and suggests the therapeutic potential of butyrate for RA.},
}

Animals
*Gastrointestinal Microbiome/drug effects
Mice
*Arthritis, Experimental/drug therapy/microbiology
Fecal Microbiota Transplantation
Male
RNA, Ribosomal, 16S/genetics
Dysbiosis/drug therapy
Fatty Acids, Volatile/metabolism
*Arthritis, Rheumatoid/drug therapy/microbiology
*Drugs, Chinese Herbal/pharmacology/therapeutic use
Mice, Inbred DBA
Butyrates/metabolism
Bacteria/classification/genetics/metabolism/drug effects
Disease Models, Animal
Bacteroidetes/drug effects

@article {pmid41308739,
year = {2025},
author = {Zhang, Y and Liu, J and Zhang, X and Cheng, S and Liu, S and Huang, A and Yu, Y and Liu, J and Chen, H and Shang, D and Yin, P and Ma, S},
title = {Rhein alleviates acute pancreatitis by inhibiting TMAO-mediated inflammatory signaling pathways and reducing acinar cell injury.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.11.056},
pmid = {41308739},
issn = {2090-1224},
abstract = {INTRODUCTION: Acute pancreatitis (AP) represents a significant global health challenge. Despite recent advances in medical treatment, the development of novel therapeutic strategies remains crucial.

OBJECTIVES: Rhein, a natural compound of the Chinese herb Rheum, shows promise in the treatment of AP. However, the exact mechanism underlying its therapeutic effect is still not fully understood.

METHODS: To investigate the association between the rhein-related gut microbiota and AP, we conducted antibiotic-mediated microbiota depletion experiments, fecal microbiota transplantation (FMT), and in vitro bacterial culture experiments. Concurrently, we performed 16S rRNA gene sequencing, metagenomic sequencing, and liquid chromatography‒mass spectrometry (LC‒MS) analyses on mouse fecal samples to characterize alterations in the microbiota and metabolome. Transcriptomic studies were also performed to elucidate the mechanisms underlying acinar cell inflammation.

RESULTS: Rhein alleviated AP by modulating the gut microbiota, as demonstrated by changes in the gut microbiota composition and improvements in AP after FMT in rhein-treated mice compared with those in cerulein-induced AP mice. Specifically, rhein is concentrated mainly in the stomach and intestines, where it exerts anti-inflammatory effects on acinar cells by antagonizing the TLR4/NF-κB/NLRP3 signaling pathway activated by trimethylamine-N-oxide (TMAO). This mechanism is associated with lipid peroxidation and necrosis mediated by oxidative stress. Clinically, disease severity in patients with AP is positively correlated with serum TMAO concentration.

CONCLUSION: Rhein alleviates AP by modulating the intestinal microbiota to reduce TMAO production, thereby suppressing TMAO-induced activation of the TLR4/NF-κB/NLRP3 signaling pathway and inhibiting acinar cell inflammation.},
}

@article {pmid41308392,
year = {2025},
author = {Lv, Y and Yang, L and Li, W and Hu, Y and Zhu, B and Zhou, M and Ye, Y and Ding, Z and Zhou, F},
title = {Tetrastigma hemsleyanum polysaccharides alleviate inflammatory bowel disease via the gut microbiota-SCFA-GPR43 signaling axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157523},
doi = {10.1016/j.phymed.2025.157523},
pmid = {41308392},
issn = {1618-095X},
abstract = {INTRODUCTION: This study investigates the protective mechanism of Tetrastigma hemsleyanum polysaccharides (THP) against inflammatory bowel disease (IBD) by focusing on its interactions with gut microbiota and metabolites.

OBJECTIVES: The study aims to elucidate how THP exerts anti-inflammatory effects on IBD through modulating gut microbiota and activating relevant signaling pathways.

METHODS: A dextran sulfate sodium (DSS)-induced IBD mouse model was used. Antibiotic-treated mice showed that THP's protective effect is microbiota-dependent. Fecal microbiota transplantation (FMT) from THP-treated donors replicated the therapeutic benefits in recipient mice. In vivo studies with GPR43 agonists/inhibitors and in vitro experiments in GPR43-knockdown HT-29 cells explored the signaling pathways. A Caco-2/HT-29 co-culture model assessed the direct protection of intestinal epithelial cells by THP-derived metabolites. 16S rRNA sequencing and metabolomics analyzed microbiota and metabolic changes.

RESULTS: THP's protective effect was abolished in microbiota-depleted mice. FMT confirmed the microbiota-mediated effect. THP suppressed intestinal inflammation via the GPR43/β-arrestin2-JNK pathway. THP-derived metabolites directly protected intestinal epithelial cells. THP modulated gut microbiota, increased short-chain fatty acid (SCFA) production, and stimulated Resolvin E1 biosynthesis, which were associated with inflammation resolution and epithelial repair.

CONCLUSION: THP exerts anti-colitic effects by modulating gut microbiota, activating GPR43-mediated signaling, and enhancing pro-resolving lipid mediators, showing potential for IBD treatment.},
}

@article {pmid41308390,
year = {2025},
author = {Fan, Q and Tao, X and Huang, H and Jiang, S and Ren, H and Liu, Y and Yang, C and Wang, Y and Yan, K and Li, J and Zhao, C and Li, X},
title = {Evodiamine relieves ulcerative colitis through reinventing the communication of "host-gut microbiota-macrophages".},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157541},
doi = {10.1016/j.phymed.2025.157541},
pmid = {41308390},
issn = {1618-095X},
abstract = {BACKGROUND AND PURPOSE: Accumulating evidence suggests that Evodiamine (EVO) exerts anti-inflammatory properties in ulcerative colitis (UC). Macrophages serve as driving factors of inflammation and the crosstalk within the "host-gut microbiota-macrophages" is considered essential in the pathogenesis of UC, however the underlying connections and mechanisms involved remained unclear. This study aimed to investigate how EVO modulates macrophages polarization balance in UC model through remodeling of host-microbiota interactions.

METHODS: UC models were induced in zebrafish and C57BL/6J mice through trinitro-benzene-sulfonic acid (TNBS) and dextran sulfate sodium salt (DSS), respectively. The key indicators of intestinal inflammation, macrophage polarization ratio in colon, colon transcriptomics and fecal microbiota were detected. Additionally, fecal microbiota transplantation (FMT) experiment was conducted to determine whether EVO ameliorates UC symptoms by regulating the intestinal microbiota and subsequently influencing M1/M2 macrophage polarization balance.

RESULTS: We found that EVO administration significantly alleviated intestinal tissue damage in both zebrafish and murine models of UC. Additionally, EVO treatment restored the M1/M2 macrophage polarization balance in the intestinal tissue of UC mice, and 16S rRNA analysis indicated that EVO alleviated the intestinal inflammation by modulating the composition of the intestinal microbiota. Furthermore, antibiotics and FMT experiments confirmed that modulation of M1/M2 macrophages polarization balance by EVO was mediated by the intestinal microbiota, potentially through NF-κB/STAT3 and interferon regulatory factor 5 (IRF5) pathway.

CONCLUSIONS: EVO remodeled the communication of "host-gut microbiota-macrophages" by regulating the NF-κB/STAT3 and IRF5 pathway, thereby providing novel perspectives into underling mechanism of EVO in the therapeutic effects against UC.},
}

@article {pmid41308055,
year = {2025},
author = {Oprea, A and Steinman, J and Huang, G and Soyinka, O and Brookbank, M and Abesteh, J and Hartman, M and McEvoy, A and Dionne, JC and Milev, R and Samaan, Z},
title = {Oral Methods of Microbiota Manipulation for Depression Symptoms: A Systematic Review: Méthodes orales de manipulation du microbiote pour traiter les symptômes de dépression : Une revue systématique.},
journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie},
volume = {},
number = {},
pages = {7067437251394369},
doi = {10.1177/07067437251394369},
pmid = {41308055},
issn = {1497-0015},
abstract = {ObjectiveThe effectiveness of current treatment options for depressive symptoms has been widely investigated with acknowledgment that some patients were either not adequately responding to treatment, finding the existing treatment intolerable, or otherwise prefer alternative options. There is increasing interest in microbiota modulation as an alternate form of depression treatment, with a growing number of trials and reviews on the subject published in the last five years. This systematic review aimed to analyze all completed randomized control trials (RCTs) that assessed depression symptoms in adults not using antidepressants, before and after oral methods of microbiota manipulation.MethodAll completed parallel-arm RCTs that assessed depression symptoms in adult participants before and after oral methods of microbiota manipulation were retrieved from four databases, MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. Data on study and intervention characteristics as well as RCT conclusions were collected independently and in duplicate, and each study's findings were summarized individually. Risk of bias was completed.ResultsWe included 66 RCTs in our review, 34 of which concluded significant differences between the intervention and control group in depressive symptom using different interventions and measures. Of the 66 trials, 54 used probiotic interventions, seven used prebiotic, eight used synbiotic and two used oral fecal microbiota transplantation. Wide variation was observed in studies' design, intervention composition and consumption methods across all 66 RCTs. No statistical synthesis or meta-analyses were possible due to the wide variety of interventions, measures and outcomes.ConclusionsThe heterogeneity of the existing RCTs did not allow for concrete conclusions on whether oral microbiota manipulation interventions are viable alternative treatment options for adults experiencing depression symptoms. We encourage the development of standardized guidelines for the design and reporting of microbiota studies in depression for the possibility of future intervention efficacy testing.},
}

@article {pmid41306971,
year = {2025},
author = {Han, T and Zhang, Y and Zheng, G and Guo, Y},
title = {From pathogenic mechanisms to therapeutic perspectives: a review of gut microbiota and intestinal mucosal immunity in inflammatory bowel disease.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1704651},
pmid = {41306971},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunity, Mucosal ; *Intestinal Mucosa/immunology/microbiology ; *Inflammatory Bowel Diseases/therapy/immunology/microbiology/etiology ; Animals ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; },
abstract = {Inflammatory bowel diseases (IBDs), which comprises Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial disorder with an as-yet undetermined etiology, with its global incidence rising rapidly, particularly in developing and Western countries. Although the exact etiology remains unclear, recent research implicates genetic predisposition, environmental factors, gut microbiota, and immune responses in the pathogenesis of IBD. Notably, dysbiosis of the gut microbiota-characterized by a reduction in the abundance and diversity of specific bacterial genera-has been suggested as a potential trigger for the onset of IBD, accompanying with dysregulated intestinal mucosal immunity involving in immune cells and nonimmune cells. Understanding and restoring the imbalanced gut microbiota, as well as identifying key bacterial species involved in IBD, are critical for elucidating disease mechanisms and developing therapeutic strategies. In this review, we explore the role of gut microbiota and intestinal mucosal immunity in the pathogenesis of IBD and offers insights into microbiota-centered therapeutic interventions, including probiotics, fecal microbiota transplantation, and microbial metabolites, that aim to modulate the gut microbiota for the treatment of IBD.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Immunity, Mucosal
*Intestinal Mucosa/immunology/microbiology
*Inflammatory Bowel Diseases/therapy/immunology/microbiology/etiology
Animals
Dysbiosis/immunology
Fecal Microbiota Transplantation
Probiotics/therapeutic use

@article {pmid41306279,
year = {2025},
author = {Feng, S and Wang, J and Si, X and Lu, S and Lu, C and Gao, Z and Yang, J and Wu, J and He, X and Wu, L},
title = {Washed microbiota transplantation: candidates for a novel strategy for ameliorating autism spectrum disorder.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1688325},
pmid = {41306279},
issn = {1664-302X},
abstract = {Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder with an increasing global incidence, imposing substantial burdens on both society and affected families. The pathogenesis of ASD is complex, involving genetic, environmental, and other factors. Notably, children with ASD often exhibit gut microbiota dysbiosis, and the relationship between gut microbiota and ASD has garnered growing attention. Current treatments for ASD remain limited and unsatisfactory. As an emerging therapeutic approach, Washed Microbiota Transplantation (WMT) reduces undigested food residues, fungi, parasite eggs, and pro-inflammatory metabolites, thereby lowering the incidence of adverse clinical events. WMT also addresses ethical and aesthetic concerns associated with Fecal Microbiota Transplantation (FMT), enhances treatment safety, and offers new hope for ASD management. This review integrates global literature to analyze the latest findings on ASD epidemiology, societal impacts, existing therapies, and clinical research on WMT, aiming to provide scientific evidence for the clinical application of WMT in ASD treatment.},
}

@article {pmid41305918,
year = {2025},
author = {Shao-Yu, Y and Niu, D and Chen, J and Li, WY and Wang, X and Meng, QW and Song, WJ and Yang, YG and Wang, H and Li, RR and Li, BY and Zhang, LG and Hu, CJ and Xu, LF and Wang, HH and Zhang, L and Liang, CZ and Du, HX},
title = {Antibiotic cocktail-induced changes in gut microbiota drive alteration of bile acid metabolism to restrain Th17 differentiation through the FXR-NLRP3 axis.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2582944},
doi = {10.1080/19490976.2025.2582944},
pmid = {41305918},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Th17 Cells/drug effects/immunology/cytology ; Male ; *Bile Acids and Salts/metabolism ; *Anti-Bacterial Agents/pharmacology/administration & dosage ; Mice ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Humans ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Mice, Inbred C57BL ; Cell Differentiation/drug effects ; Fecal Microbiota Transplantation ; *Prostatitis/immunology/microbiology/drug therapy ; Disease Models, Animal ; Interleukin-17 ; RNA, Ribosomal, 16S/genetics ; },
abstract = {Antibiotics influence both gut microbial composition and immune regulation, but the detailed mechanisms are still undefined. Shifts in the microbiome caused by antibiotic exposure can modulate immune activity through various pathways. Therefore, we aimed to explore how antibiotics affect immune-inflammation by regulating Th17 cells through the gut microbiota of mice with experimental autoimmune prostatitis (EAP). Antibiotic-driven shifts in gut microbial communities and metabolite profiling in EAP mice were performed by integrating 16S rRNA sequencing with mass spectrometry-driven metabolomic analysis. Antibiotic cocktail (ABX) therapy mitigated EAP, modified the gut microbiome composition, and influenced bile acid metabolism. Fecal microbiota transplantation (FMT) using microbiota from ABX-treated feces into EAP mice effectively altered gut microbiome composition and alleviated disease symptoms, indicating that microbiome intervention reduces autoimmune inflammation and decreases deoxycholic acid (DCA) in mice. Subsequent experiments demonstrated that DCA suppresses farnesol X receptor (FXR) expression which can inhibit the NLRP3‒ IL17A axis, thus promoting Th17 cell development and exacerbating inflammatory cell infiltration of the prostate. Our initial clinical examination of patients with prostatitis and antibiotic treatment indicated that bile acid metabolism and Th17 cell development are affected by antibiotic therapy. This work revealed that antibiotic-induced gut microbiota dysbiosis decreases the bile acid metabolite DCA, further restraining Th17 cell differentiation via the FXR‒NLRP3 axis to alleviate autoimmune prostatitis. Our results reveal new perspectives regarding the interconnected dynamics of antibiotics, gut microbiota, bile acid metabolism, and immune regulation, with potential relevance for therapies targeting immune-mediated diseases.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Th17 Cells/drug effects/immunology/cytology
Male
*Bile Acids and Salts/metabolism
*Anti-Bacterial Agents/pharmacology/administration & dosage
Mice
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
Humans
*Receptors, Cytoplasmic and Nuclear/metabolism/genetics
Mice, Inbred C57BL
Cell Differentiation/drug effects
Fecal Microbiota Transplantation
*Prostatitis/immunology/microbiology/drug therapy
Disease Models, Animal
Interleukin-17
RNA, Ribosomal, 16S/genetics

@article {pmid41305382,
year = {2025},
author = {Zhang, Z and Kang, W and Mi, Y and Zhong, X and He, Y},
title = {The Microbiota-Gut-Brain Axis in Autism: Associations, Causal Inference, and Interventions-A Narrative Review.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {11},
pages = {},
doi = {10.3390/pathogens14111145},
pmid = {41305382},
issn = {2076-0817},
support = {Grant No. LCYSSQ20220823091203008//the Shenzhen Clinical Research Center for Gastroenterology/ ; Grant No. A2402008//the Shenzhen Medical Research Fund/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome ; *Brain ; Probiotics/therapeutic use ; *Autism Spectrum Disorder/microbiology/therapy ; *Autistic Disorder/microbiology/therapy ; *Brain-Gut Axis ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; },
abstract = {Autism spectrum disorder is markedly heterogeneous and frequently accompanied by gastrointestinal symptoms that often correlate with behavioral phenotypes. Emerging evidence suggests that the microbiota-gut-brain axis may contribute to these associations through multiple bidirectional communication routes-including neural, immune, and endocrine pathways, as well as microbial metabolites such as short-chain fatty acids and tryptophan-kynurenine intermediates. This narrative review synthesizes clinical, mechanistic, and interventional evidence published between January 2010 and July 2025, clarifies the extent to which current data support association versus causation, evaluates key confounding factors, summarizes evidence for interventions such as probiotics, prebiotics, and fecal microbiota transplantation, and outlines future directions for precision research and targeted interventions based on functional pathways and stratified subgroups.},
}

Humans
*Gastrointestinal Microbiome
*Brain
Probiotics/therapeutic use
*Autism Spectrum Disorder/microbiology/therapy
*Autistic Disorder/microbiology/therapy
*Brain-Gut Axis
Fecal Microbiota Transplantation
Prebiotics/administration & dosage

@article {pmid41304963,
year = {2025},
author = {Golčić, M and Radoš, L and Skočilić, I and Badovinac, I and Hauser, G and Krznarić Zrnić, I and Šantić, M and Fučkar Čupić, D and Francetić, S and Lisica, K and Juras, L and Škrtić, M and Bešvir Džubur, A and Šeparović, R and Tomašić, V and Tečić Vuger, A and Mikolašević, I},
title = {Fecal Microbiota Transplantation in Refractory Immune-Mediated Colitis: Case Series and Review of the Literature.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {11},
pages = {},
doi = {10.3390/ph18111719},
pmid = {41304963},
issn = {1424-8247},
abstract = {Background/Objectives: Immune checkpoint inhibitors (ICI) represent a significant breakthrough in cancer management, but they can cause adverse effects such as immune-mediated colitis (IMC). The standard first-line treatment is corticosteroids, and second-line treatment is infliximab or vedolizumab. However, a proportion of immune-mediated colitis (IMC) cases are refractory to immunosuppressive treatment, which has led to the exploration of novel approaches such as fecal microbiota transplantation. Methods: We present two patients who both developed grade III IMC following application of durvalumab and pembrolizumab, respectively. Both patients were refractory to corticosteroid therapy, while the first one also showed no improvement to infliximab. We performed two separate applications of FMT on both patients, from different donors, as a rescue treatment. Results: After unsuccessful immunosuppressive treatment and following rescue FMT, both patients demonstrated a rapid and sustained improvement in inflammatory markers, clinical symptoms, quality-of-life scores, and colonoscopy findings, without additional immunosuppressive treatment. Conclusions: FMT appears to be safe and a potentially effective treatment option for patients with refractory IMC both as second- and third-line therapy options. Continued efforts toward rigorous donor screening, use of standardized biobanks, and standardizing FMT protocols will further enhance safety and reproducibility.},
}

@article {pmid41304215,
year = {2025},
author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV},
title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112529},
pmid = {41304215},
issn = {2076-2607},
support = {DPI/BCE nº 01/2025//University of Brasilia/ ; FAPDF nº 09/2023//Fundação de Apoio à Pesquisa do Distrito Federal/ ; },
abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.},
}

@article {pmid41304202,
year = {2025},
author = {Feng, JJ and Maddirala, NR and Saint Fleur, A and Zhou, F and Yu, D and Wei, F and Zhang, Y},
title = {Gut Microbiome and Immune System Crosstalk in Chronic Inflammatory Diseases: A Narrative Review of Mechanisms and Therapeutic Opportunities.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112516},
pmid = {41304202},
issn = {2076-2607},
abstract = {The gut microbiota, a complex community of trillions of microorganisms residing in the gastrointestinal tract, plays a vital role in maintaining host health and regulating a wide range of physiological functions. Advances in molecular biology have greatly expanded our understanding of the dynamic interactions between the gut microbiome and the immune system. Disruption of this microbial community, known as dysbiosis, can compromise epithelial barrier integrity, trigger aberrant immune activation, and lead to the production of proinflammatory metabolites. These changes are increasingly recognized as contributing factors in the pathogenesis of chronic inflammatory diseases. Emerging research highlights the gut microbiota as a key modulator of immune homeostasis, influencing both local and systemic inflammatory processes during the initiation and progression of these diseases. Understanding the mechanisms underlying gut microbiota-immune interactions will offer new avenues for therapeutic interventions. This review focuses on six representative chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, asthma, and vasculitis, all of which are characterized by dysregulated immune responses and persistent inflammation. Our goal is to synthesize the recent research on the role of gut microbiome in the pathogenesis of the diseases listed above and provide insights into the development of microbiota-based therapies, particularly fecal microbiota transplant, dietary modifications, prebiotic and probiotic interventions, for their treatment.},
}

@article {pmid41304151,
year = {2025},
author = {Reveles, KR and Meehan, J and Tillotson, G},
title = {Fecal Microbiota Transplantation in Animals: Therapeutics, Conservation, and Farming.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112465},
pmid = {41304151},
issn = {2076-2607},
abstract = {Fecal microbiota transplantation (FMT) is increasingly used in both human and veterinary settings to restore gut microbiota and promote health. Advances in sequencing technologies and microbiome analysis have expanded our understanding of microbial communities and enabled broader FMT applications. As insights grow into what constitutes a healthy microbiome, interest in using FMT across a range of animal contexts has also increased. This narrative review highlights recent progress in the use of FMT to improve the welfare of farm animals, manage infectious and chronic conditions in companion animals, and support the health of wildlife in conservation and reintroduction programs. Representative examples from each domain are discussed.},
}

@article {pmid41304131,
year = {2025},
author = {Lv, D and Han, N and Liu, H and Tang, H},
title = {Hepatitis B Virus-Related Liver Disease and Gut Microbiota: An Updated Review.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112445},
pmid = {41304131},
issn = {2076-2607},
abstract = {Although gut microbiota plays a pivotal role in numerous biological functions (e.g., energy, nutrients, metabolism, and immunological processes), growing evidence demonstrates that the gut microbiota is involved in the progression of liver diseases. The liver can be greatly influenced by alterations in intestinal microbiota due to increased gut permeability, allowing for the entry of bacterial products into the liver through the gut-liver axis. Recently, clinical and experimental research findings have demonstrated that microbiota dysbiosis plays an important role in the pathogenesis and progression of HBV-related liver diseases. In this review, we provide an overview of the gut microbiota and the microbiota-gut-liver axis in health; review HBV infection interactions with microbiota; discuss the role of microbiota dysbiosis in the pathogenesis of HBV-related liver disease, such as chronic HBV infection, liver cirrhosis, and hepatocellular carcinoma; and, finally, assess the potential for microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation. This review will provide novel insights into individualized therapy for CHB patients based on gut microbiota alteration.},
}

@article {pmid41303703,
year = {2025},
author = {Qassadi, FI and Johnson, C and Robinson, K and Griffin, R and Polytarchou, C and Kao, D and Kim, DH and Griffiths, RL and Zhu, Z and Monaghan, TM},
title = {Untargeted Metabolomics Identifies Faecal Filtrate-Derived Metabolites That Disrupt Clostridioides difficile Metabolism and Confer Gut Barrier Cytoprotection.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
doi = {10.3390/ijms262211221},
pmid = {41303703},
issn = {1422-0067},
support = {1074742634//Saudi Ministry of Higher Education/ ; },
mesh = {*Clostridioides difficile/metabolism ; *Metabolomics/methods ; Humans ; *Feces/microbiology/chemistry ; *Clostridium Infections/metabolism/therapy/microbiology ; Fecal Microbiota Transplantation ; *Cytoprotection ; Metabolome ; Gastrointestinal Microbiome ; *Intestinal Mucosa/metabolism/microbiology ; Female ; Male ; },
abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a major therapeutic challenge. Although faecal microbiota transplantation (FMT) is highly effective and thought to restore microbial composition and metabolic function, the mechanisms underlying its success are not fully understood. In particular, the contribution of non-bacterial components such as soluble metabolites remains unclear. Therefore, further investigation is needed to identify the mechanistic drivers of FMT efficacy and clarify how non-bacterial factors contribute to therapeutic outcomes. Here, we applied untargeted three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) to profile faecal metabolic reprogramming in rCDI patients pre- and post-FMT, alongside C. difficile cultures exposed to sterile faecal filtrates. FMT induced extensive metabolic shifts, restoring glyoxylate/dicarboxylate and glycerophosphoinositol pathways and normalising disrupted bile acid and amino acid profiles. Faecal filtrate exposure caused strain-specific metabolic disruption in C. difficile, depleting proline, fumarate and succinate while enriching tryptophan. While multiple metabolite classes were profiled, the most significant functional changes were observed in lipids. Lipidomics identified >3.8-fold enrichment of phosphatidylinositol (PI) species, which localised to bacterial membranes and conferred cytoprotection against C. difficile toxins and other epithelial insults. Spatial metabolomics imaging revealed, for the first time, metabolite compartmentalisation within C. difficile, with proline and succinate broadly distributed across the cell surface and fumarate confined to distinct microdomains, highlighting functional heterogeneity in pathogen metabolism. Collectively, these findings demonstrate that soluble metabolites within faecal filtrates mediate pathogen suppression and epithelial barrier protection, establishing metabolite-driven mechanisms underlying FMT efficacy and identifying PI lipids as candidate post-biotic therapeutics for rCDI.},
}

*Clostridioides difficile/metabolism
*Metabolomics/methods
Humans
*Feces/microbiology/chemistry
*Clostridium Infections/metabolism/therapy/microbiology
Fecal Microbiota Transplantation
*Cytoprotection
Metabolome
Gastrointestinal Microbiome
*Intestinal Mucosa/metabolism/microbiology
Female
Male

@article {pmid41301795,
year = {2025},
author = {Seguiti, C and Tettoni, E and Pezzuto, E and Gerardi, V and Quadarella, A and Cesaro, P and Colombini, P},
title = {Clostridioides difficile Infection in Special Populations: Focus on Inflammatory Bowel Disease-A Narrative Review from Pathogenesis to Management.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112702},
pmid = {41301795},
issn = {2227-9059},
abstract = {Clostridioides difficile infection (CDI) is a major complication in inflammatory bowel disease (IBD), due to coexistence of altered microbiota, chronic inflammation, and immune dysregulation. This narrative review summarizes recent evidence on the epidemiology, pathogenesis, risk factors, diagnosis, and management of CDI in IBD. Overall, IBD patients have a four- to five-fold higher risk of CDI than the general population and face more severe courses, higher rates of hospitalization, colectomy, recurrence, and mortality. Pathogenesis involves profound dysbiosis with loss of butyrate-producing Firmicutes and Bacteroidetes, bile acid imbalance that promotes spore germination, and enhanced toxin effects on an already inflamed mucosa. Major risk factors include active colonic disease, broad-spectrum antibiotic exposure, prolonged hospitalization, and corticosteroid or combined immunosuppressive therapy. Diagnosis requires careful integration of stool assays with clinical evaluation, supported by endoscopy or imaging when needed, to distinguish infection from IBD flares. Recommended first-line treatments are fidaxomicin or oral vancomycin, reserving fecal microbiota transplantation for recurrent or high-risk cases. Optimal IBD control is essential to reduce both primary and recurrent infection. CDI and IBD share a mutual pathogenic interplay in which microbial, immune, and therapeutic factors from each condition drive and magnify the other. Early recognition, guideline-based antibiotic therapy, judicious use of immunosuppression, and microbiota-based preventive strategies are crucial to improve patient outcomes and limit recurrence, thus reducing healthcare costs.},
}

@article {pmid41301443,
year = {2025},
author = {Papavassiliou, KA and Sofianidi, AA and Spiliopoulos, FG and Margoni, A and Papavassiliou, AG},
title = {Emerging Issues Regarding the Effects of the Microbiome on Lung Cancer Immunotherapy.},
journal = {Biomolecules},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/biom15111525},
pmid = {41301443},
issn = {2218-273X},
mesh = {Humans ; *Lung Neoplasms/therapy/microbiology/immunology ; *Immunotherapy/methods ; *Microbiota/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; },
abstract = {Lung cancer remains the deadliest malignancy, with limited effective and long-term therapeutic options. Immunotherapy has revolutionized the therapeutic landscape of lung cancer. However, not everyone with lung cancer responds to immunotherapy, while, inpatients who temporarily derive clinical benefit, resistance eventually develops. The host microbiome has emerged as a pivotal player in cancer growth and progression. It has been implicated in the intricate connections between immune cells and tumor cells, ultimately augmenting immunotherapy efficacy in solid tumors, while simultaneously mitigating the immune-related adverse events associated with this type of treatment. Notably, lung cancer patients who obtain benefit from immunotherapy have been found to be colonized with specific bacterial populations, and it is this observation that the scientific community is trying to exploit, aspiring to improve lung cancer immunotherapy response rates. Delving deeper into the molecular mechanisms underpinning the effects of the microbiome on immunotherapy is an area that we should pay attention to if we want to utilize microbiome modulation in everyday clinical practice. Fecal microbiota transplantation, probiotics, targeted antibiotic interventions, and dietary modifications are among the strategies that are under investigation in clinical trials, with the ultimate endpoint of lengthening the life expectancy of lung cancer patients.},
}

Humans
*Lung Neoplasms/therapy/microbiology/immunology
*Immunotherapy/methods
*Microbiota/immunology
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Animals

@article {pmid41300985,
year = {2025},
author = {De Lucia, SS and Nista, EC and Candelli, M and Archilei, S and Deutschbein, F and Capuano, E and Gasbarrini, A and Franceschi, F and Pignataro, G},
title = {Microbiota and Pancreatic Cancer: New Therapeutic Frontiers Between Engineered Microbes, Metabolites and Non-Bacterial Components.},
journal = {Cancers},
volume = {17},
number = {22},
pages = {},
doi = {10.3390/cancers17223618},
pmid = {41300985},
issn = {2072-6694},
abstract = {Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal human malignancies, with five-year survival rates showing only marginal improvement despite decades of intensive research. Its dismal prognosis reflects a combination of intrinsic biological aggressiveness, late clinical presentation, and marked resistance to standard therapies, underscoring the urgent need for innovative diagnostic and therapeutic approaches. Growing evidence indicates that the microbiome is a modifiable factor influencing the onset, progression, and treatment response of PDAC. Microbial communities originating from the gut, oral cavity, and even the tumor microenvironment can shape carcinogenic pathways, modulate immune activity, and alter the efficacy of chemotherapy and immunotherapy. In addition to bacteria, fungal and viral populations are emerging as relevant contributors within this complex ecosystem. This review provides a comprehensive overview of the current mechanistic and translational evidence linking the microbiome to PDAC biology and therapy. It further explores microbiota-targeted interventions-such as probiotics, postbiotics, engineered bacterial strains, bacteriophages, oncolytic viruses, and fecal microbiota transplantation-as promising adjuncts to conventional treatments. A deeper understanding of host-microbiome interactions could yield novel biomarkers and open innovative avenues for precision medicine in PDAC, ultimately improving patient outcomes and reshaping therapeutic paradigms. Integrating microbiome-based strategies into PDAC management may thus represent a crucial step toward more effective and personalized oncologic care.},
}

@article {pmid41300676,
year = {2025},
author = {Marano, G and Sfratta, G and Marzo, EM and Cozzo, G and Abate, F and Traversi, G and Mazza, O and Capristo, E and Gaetani, E and Mazza, M},
title = {The Pediatric Microbiota-Gut-Brain Axis: Implications for Neuropsychiatric Development and Intervention.},
journal = {Children (Basel, Switzerland)},
volume = {12},
number = {11},
pages = {},
doi = {10.3390/children12111561},
pmid = {41300676},
issn = {2227-9067},
abstract = {BACKGROUND: The gut microbiota plays a crucial role in brain development and function, especially in early life. Disruptions in the pediatric microbiota-gut-brain axis have been linked to neurodevelopmental and psychiatric disorders. We hypothesize that early-life dysbiosis can perturb neurodevelopment via the pediatric microbiota-gut-brain axis, increasing risk and/or severity of neuropsychiatric outcomes, and that microbiota-targeted strategies may mitigate this risk.

METHODS: We conducted a narrative review by searching PubMed, Scopus, and Web of Science up to January 2025 for studies addressing pediatric microbiota, neuropsychiatric development, and interventions. Human and animal studies were included if they provided mechanistic or clinical insights.

RESULTS: Key determinants of microbiota development in childhood include mode of delivery, feeding practices, antibiotic exposure, diet, and environment. Altered microbial composition has been associated with autism spectrum disorder, attention-deficit/hyperactivity disorder, mood disorders, anxiety, and anorexia nervosa. Mechanistic pathways involve immune modulation, neural signaling (including the vagus nerve and enteric nervous system), and microbial metabolites such as short-chain fatty acids. Interventions targeting the microbiota-ranging from dietary strategies and probiotics to psychobiotics and fecal microbiota transplantation-show promise but require further pediatric-focused trials.

CONCLUSIONS: The pediatric microbiota-gut-brain axis represents a critical window for neuropsychiatric vulnerability and intervention. Early-life strategies to support a healthy microbiota may help reduce the risk or severity of psychiatric disorders. Future research should prioritize longitudinal pediatric cohorts and clinical trials to translate mechanistic insights into precision interventions.},
}

@article {pmid41299731,
year = {2025},
author = {Zhao, Y and Li, H and Xu, J and Li, H and Bao, L and Wu, K and Qiu, M and Yu, H and Shang, S and He, Y and Yuan, C and Zhang, N and Hu, X and Fu, Y and Li, W and Zhao, C and Wang, J},
title = {Phytosphingosine contributes gut microbiota metabolism to alleviate low-grade endotoxemia-induced mastitis.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02266-9},
pmid = {41299731},
issn = {2049-2618},
support = {32330105//National Natural Science Foundation of China/ ; 2023M741348//China Postdoctoral Science Foundation/ ; },
abstract = {BACKGROUND: Recently, evidence has indicated that mastitis is closely associated with the ruminal dysbiosis caused by subacute ruminal acidosis (SARA) and subsequent low-grade endotoxemia (LGE). However, whether and how ruminal metabolic dysbiosis influences SARA-associated mastitis is still unclear.

RESULTS: Using untargeted metabolomics, we found that cows with SARA-associated mastitis exhibited altered ruminal metabolic profiles, particularly a reduced level of phytosphingosine (PS), compared to healthy cows. Oral administration of PS to mice alleviated LGE-induced mastitis, as evidenced by attenuated mammary injury and improved function of mammary tight junctions (TJs). Furthermore, we demonstrated that LGE induced significant gut dysbiosis, characterized by increased abundances of opportunistic pathogens such as Enterococcus, which was mitigated by PS treatment. Interestingly, transplantation of both fecal microbiota (FMT) and matched sterile supernatant (FST) from PS-treated mice alleviated LGE-induced mastitis, restored the blood-milk barrier, and modulated the gut microbiota in recipient mice following LGE exposure. Additionally, PS and PS-FMT treatments increased the abundances of fecal short-chain fatty acid (SCFA) producers, accompanied by elevated fecal SCFA levels, particularly butyric acid, in PS- and PS-FMT-treated mice. Butyric acid was negatively correlated with mammary inflammatory markers, and butyrate administration attenuated LGE-induced mastitis in mice. Mechanistically, butyrate promotes M2 macrophage polarization and inhibits NF-κB and NLRP3 inflammasome activation via G-protein-coupled receptor 41 (GPR41).

CONCLUSIONS: Collectively, our results demonstrate that gut microbiota from PS-dosed mice alleviate LGE-induced mastitis in mice by promoting SCFA production and regulating macrophage polarization. Our findings provide deeper insights into gut dysbiosis-associated mastitis and highlight the potential of modulating gut microbiota and its metabolism as a strategy for managing mastitis and other related diseases. Video Abstract.},
}

@article {pmid41299728,
year = {2025},
author = {Vaziri, Y and Olia, JBH and Avci, CB and Nourazarian, A},
title = {Molecular mechanisms of gut microbiota dysbiosis and metabolites in Alzheimer's disease pathogenesis: implications for precision therapeutics.},
journal = {Molecular brain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13041-025-01263-1},
pmid = {41299728},
issn = {1756-6606},
abstract = {Alzheimer's disease (AD) originates from both central and peripheral pathways. The gut microbiota is a clear risk factor. In AD, microbiota imbalances drive immune system activation, disrupt protective barriers, and alter neuromodulatory signaling. Additionally, gut microbiota dysbiosis has been identified as a risk factor for AD. Recent research indicates that dysbiosis of the microbiota in AD is linked to immune activation, barrier dysfunction, and neuromodulatory signaling. Studies of AD pathology reveal that short-chain fatty acids, indole derivatives, and bile acids can have both protective and harmful effects. New strategies, such as probiotics, dietary changes, and fecal microbiota transplantation, may influence disease progression in AD. However, conflicting methods, unaccountable motives, and ethical concerns surrounding microbiome interventions pose significant hurdles. To translate findings related to the gut-brain axis into effective solutions, we need standardized multi-omics approaches, personalized therapies, and oversight from regulatory authorities. Ultimately, leveraging insights from the gut microbiome holds great promise for transforming how we diagnose, prevent, and treat AD.},
}

@article {pmid41298101,
year = {2025},
author = {Liu, CS and Merrick, B and Taboun, ZS and Mullish, BH and Goldenberg, SD and Terveer, EM and Porcari, S and Bradbury, RS and Ianiro, G and Ng, SC and , and Kao, D and Kuijper, E},
title = {Towards optimising and standardising donor screening for faecal microbiota transplantion.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2025-336532},
pmid = {41298101},
issn = {1468-3288},
abstract = {Rigorous donor screening is fundamental for the safe and effective delivery of faecal microbiota transplantion (FMT) services, whether in the treatment of Clostridioides difficile infection or within microbiome intervention clinical trials. Donor screening is of paramount importance given the potential risk of pathogen transmission-a feared complication. While rare in practice, documented cases of FMT-associated infections have resulted in significant morbidity and even mortality. Despite the importance of screening, evidence-based approaches to developing donor-screening protocols are lacking. Inadequate screening for transmissible pathogens may lead to infections in recipients, while overly cautious screening for pathogens with negligible transmission potential could strain healthcare resources and unnecessarily exclude donors, who are already in limited supply. This review aimed to evaluate the evidence underpinning current FMT donor screening protocols. We began by comparing protocols from major FMT guidelines and manufacturers, highlighting their differences in lists of screened pathogens, laboratory assays and clinical characteristics used for donor selection. We critically appraised the existing literature on transmission dynamics for pathogens. These findings were incorporated into a Delphi process with an expert panel group to develop a rational and streamlined screening approach. We further emphasised the importance of maintaining transparency with regard to donor recruitment, screening, monitoring and traceback record keeping. Finally, we explored future directions in donor screening, including approaches to monitoring emerging pathogens and the potential for integration of new technologies, such as metagenomic assays, to enhance and refine donor selection.},
}

@article {pmid41134466,
year = {2025},
author = {Strzępa, A and Szczepanik, M},
title = {The role of microbiota modulation in preventing Alzheimer's disease- a review.},
journal = {Pharmacological reports : PR},
volume = {77},
number = {6},
pages = {1468-1490},
pmid = {41134466},
issn = {2299-5684},
support = {N43/DBS/000345//Polish Ministry of Science and Higher Education/ ; },
abstract = {Alzheimer’s disease (AD) is the most common form of dementia, and its incidence is projected to triple worldwide over the next 25 years. The most prevalent form, late-onset Alzheimer’s disease (LOAD), develops in genetically predisposed individuals exposed to environmental risk factors. Hallmarks of AD include accumulation of amyloid-β (Aβ), neurofibrillary tangles (NFTs), neuroinflammation, and mitochondrial dysfunction, resulting in oxidative stress, impaired glucose metabolism, and cognitive decline. Such metabolic disruptions result in early cerebral glucose hypometabolism and other metabolic disruptions, including altered lipid and branched-chain amino acid profiles. Recent evidence suggests that gut microbiota alterations, although individually variable, are a consistent and influential factor in AD progression via inflammatory and metabolic pathways. This narrative review explores therapeutic interventions targeting the gut-brain axis, including fecal microbiota transplantation (FMT), probiotic and antibiotic treatments, and dietary strategies such as the ketogenic and Mediterranean diets, as well as nutritional compounds such as omega-3 fatty acids. The aim is to evaluate the latest findings in both preclinical and clinical studies to identify multi-targeted, microbiota-based approaches for the prevention and management of AD.},
}

@article {pmid41297775,
year = {2025},
author = {Ferrini, A and He, M and Mont, MA and Goodman, SB and Parvizi, J},
title = {Osteonecrosis of the femoral head: A Dysbiotic Condition?.},
journal = {The Journal of arthroplasty},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.arth.2025.11.044},
pmid = {41297775},
issn = {1532-8406},
abstract = {Osteonecrosis of the femoral head (ONFH) is a progressive and disabling condition of the hip joint that primarily affects young and active individuals, leading to progressive collapse of subchondral bone and often secondary arthritis. Despite extensive investigation, the precise etiology often remains unclear. While high-dose corticosteroids, chronic alcohol ingestion, and smoking are known associated risk factors, approximately 20 to 30% of ONFH cases are classified as idiopathic. Recently, the concept of gut dysbiosis, i.e., disruption of the normal intestinal microbial balance, has gained increasing attention due to its systemic immunologic and metabolic implications. Dysbiosis is associated with an increase in gut permeability, leading to the translocation of bacteria and their metabolic products, including lipopolysaccharides and short-chain fatty acids (SCFAs), into the systemic circulation. This may stimulate proinflammatory cascades throughout the body, including the joints, initiating a bone remodeling process. Emerging evidence from preclinical and human research suggests that specific gut microbiota taxa may influence key mechanisms involved in the pathogenesis of ONFH. Additionally, early findings support the therapeutic potential of microbiota-targeted therapies such as probiotics, SCFAs-enriched diets, and fecal microbiota transplantation (FMT). Although a growing number of descriptive studies support this link, the current evidence remains associative rather than causal, as no longitudinal cohort studies have confirmed this relationship. Future investigations are needed to establish causality between gut dysbiosis and ONFH. To our knowledge, this review offers the first comprehensive synthesis of the literature aiming to explore current evidence and the potential link between gut dysbiosis and ONFH, highlighting future directions for microbiome-based therapeutic interventions.},
}

@article {pmid41296090,
year = {2025},
author = {Wang, M and Zeng, Y and Jin, Y and Wu, J and Li, J},
title = {Progress and Perspectives on the Estrogen-Microbiota-Brain Axis in Alzheimer's Disease.},
journal = {Neurochemical research},
volume = {51},
number = {1},
pages = {3},
pmid = {41296090},
issn = {1573-6903},
support = {No. QKHJC-ZK[2022]-260//Guizhou Provincial Science and Technology Projects/ ; NO.gzwjrs2023-005//Guizhou Provincial High level Innovative Talent Fund/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/microbiology ; *Estrogens/metabolism ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism/drug effects ; Animals ; Dysbiosis/metabolism ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder shaped by genetic, metabolic, environmental, and sex-specific factors. Emerging evidence highlights the estrogen-gut microbiota-brain (EGMB) axis as a critical framework linking endocrine regulation, microbial activity, and cognitive outcomes. Estrogen exerts neuroprotective effects by modulating synaptic plasticity, oxidative stress, amyloid and tau pathology, and neuroinflammation, while its decline during menopause increases AD vulnerability. Parallel to this, gut dysbiosis and altered microbial metabolites, particularly short-chain fatty acids (SCFAs) and secondary bile acids (sBAs), contribute to barrier dysfunction, chronic inflammation, and synaptic impairment. Importantly, estrogen remodels microbial composition and metabolite profiles, whereas microbial β-glucuronidase (β-GUS) activity sustains estrogen bioavailability, establishing a reciprocal regulatory loop. Preclinical studies demonstrate that depletion of gut microbiota diminishes estrogen's protective effects, underscoring the central role of microbial metabolites as signaling bridges.Therapeutically, these insights support the integration of hormone replacement therapy with microbiota-targeted interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Such combined strategies may synergistically enhance neuroprotection, though their efficacy depends on timing, dosage, and individual variability. Future precision approaches integrating multi-omics profiling and sex-specific stratification hold promise for identifying predictive biomarkers and optimizing treatment windows. In summary, the EGMB axis offers a mechanistic foundation for understanding sex differences in AD and a translational framework for developing individualized, multidimensional strategies for early diagnosis, prevention, and therapy.},
}

Humans
*Alzheimer Disease/metabolism/microbiology
*Estrogens/metabolism
*Gastrointestinal Microbiome/physiology
*Brain/metabolism/drug effects
Animals
Dysbiosis/metabolism

@article {pmid41294832,
year = {2025},
author = {Susiriwatananont, T and Eiamprapaporn, P and Vazquez Roque, M and Farraye, FA and Perlman, A and Chumsri, S},
title = {The Gut Microbiome as a Biomarker and Therapeutic Target of Immune Checkpoint Inhibitors: A Review for Oncologists.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/cells14221779},
pmid = {41294832},
issn = {2073-4409},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Oncologists ; *Neoplasms/drug therapy/immunology/microbiology ; Biomarkers/metabolism ; Immunotherapy/methods ; Biomarkers, Tumor/metabolism ; Animals ; Fecal Microbiota Transplantation ; },
abstract = {Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet their benefits remain limited to a subset of patients, underscoring the need for more reliable biomarkers and novel therapeutic strategies. The gut microbiome has emerged as a critical modulator of systemic immunity and a promising determinant of ICI response. Evidence links specific microbial features, taxa, and bioactive metabolites to enhanced antitumor immunity, whereas disruptions, such as antibiotic exposure, are associated with poorer outcomes. Advances in sequencing and multi-omics technologies have provided more profound insights into microbiome-immune crosstalk, though methodological heterogeneity continues to challenge reproducibility. Translational studies demonstrate that microbiome-based intervention, including fecal microbiota transplantation (FMT), biotics supplementation, and engineered microbial strains, can enhance ICI efficacy or mitigate immune-related toxicities. Despite encouraging early clinical signals, broader implementation requires methodological rigor, standardized protocols, and innovative trial designs that account for host and environmental factors. For clinicians, the most immediate strategies involve prudent antibiotic stewardship and patient enrollment in microbiome-focused clinical trials. Overall, the gut microbiome is a promising biomarker and a therapeutic target, representing a new frontier for personalizing immunotherapy and improving patient outcomes in oncology.},
}

Humans
*Gastrointestinal Microbiome/drug effects/immunology
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
*Oncologists
*Neoplasms/drug therapy/immunology/microbiology
Biomarkers/metabolism
Immunotherapy/methods
Biomarkers, Tumor/metabolism
Animals
Fecal Microbiota Transplantation

@article {pmid41293177,
year = {2025},
author = {Li, P and Wang, Y and Dong, Y and Zhang, X},
title = {Unveiling the gut-liver axis: the behind-the-scenes "manipulator" of human immune function.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1638197},
pmid = {41293177},
issn = {1664-3224},
mesh = {Humans ; *Liver/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; Animals ; Bile Acids and Salts/metabolism ; },
abstract = {The "gut-liver axis" enables bidirectional immunoregulation between the intestine and the liver through the portal venous circulation, bile acid metabolism, and the neuro-lymphatic network. This paper reviews its physiological pathways (vascular, biliary, neural, and lymphatic), immunomodulatory mechanisms (interaction of innate/adaptive immune cells, balance between inflammation and tolerance), and associations with diseases such as PSC, MAFLD, and IBD. Metabolites of gut microbiota activate immune cell receptors to regulate the differentiation of Tregs, while cytokines (such as IL-6) and chemokines (such as CCR9) drive the synergy of gut-liver immunity. In pathological conditions, dysbiosis, endotoxin translocation, and bile acid metabolic disorders trigger immunological dysregulation through this axis. Strategies such as targeted fecal microbiota transplantation and bile acid receptor (FXR) agonists show clinical potential. This paper systematically elaborates on the physiological and immunoregulatory mechanisms of the "gut-liver axis", explores the associations between its abnormalities and immune diseases, as well as the prospects of translational medicine. It is proposed that future research should deepen the analysis of single-cell interactions, conduct personalized interventions, and establish a new paradigm of "gut-liver axis medicine" to provide cross-organ solutions for the precise prevention and control of immune-related diseases.},
}

Humans
*Liver/immunology/metabolism
*Gastrointestinal Microbiome/immunology
Animals
Bile Acids and Salts/metabolism

@article {pmid41292506,
year = {2025},
author = {Arawker, MH and Habibullah, F and Baral, S and Fu, L and Sun, N and Li, H and Ji, F and Qiu, X},
title = {Microbiome Mediated Immune Crosstalk on the Gut-Thyroid Axis in Autoimmune Thyroid Disease.},
journal = {Immunological investigations},
volume = {},
number = {},
pages = {1-21},
doi = {10.1080/08820139.2025.2593335},
pmid = {41292506},
issn = {1532-4311},
abstract = {BACKGROUND: The gut microbiota plays an important role in systemic immune homeostasis and is increasingly implicated in autoimmune thyroid disease (AITD). Evidence suggests that gut dysbiosis, impaired intestinal barrier function, and altered microbial metabolites particularly short-chain fatty acids contribute to immune imbalance along the gut-thyroid axis. Although molecular mimicry between microbial and thyroid antigens has been proposed, current human evidence remains associative rather than causal.

METHODS: This review synthesized current observational, translational, and preclinical studies evaluating microbial composition, barrier integrity, microbial metabolites, and immune pathways relevant to AITD. Mechanistic insights into T-lymphocyte regulation and microbial-host interactions were integrated with emerging interventional data.

RESULTS: Gut dysbiosis in AITD is linked to reduced regulatory T-lymphocytes, expansion of Th17 cells, increased intestinal permeability, and the loss of short-chain-fatty-acid-producing taxa. Observational studies consistently report disease-associated taxonomic alterations, while preclinical models support causal pathways through barrier disruption and microbiota-driven immune activation. Early interventional approaches such as high-fiber dietary patterns, probiotics, prebiotics, and experimental fecal microbiota transplantation show modest reductions in thyroid autoantibodies in small trials, though effects are strain-specific, short-term, and not disease-modifying.

CONCLUSION: Despite largely associative human evidence, converging mechanistic findings highlight the gut microbiota as a modifiable contributor to thyroid autoimmunity. Future priorities include clarifying causality, identifying keystone microbial taxa and metabolites, and establishing standardized interventional frameworks to facilitate translation into endocrine practice.},
}

@article {pmid41292332,
year = {2025},
author = {Bø, S and Wiig, H and Juul, FE and Garborg, KK and Johnsen, PH and Bretthauer, M},
title = {Faecal microbiota transplantation for primary Clostridioides difficile infection.},
journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke},
volume = {145},
number = {14},
pages = {},
doi = {10.4045/tidsskr.25.0276},
pmid = {41292332},
issn = {0807-7096},
mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; Female ; Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use/adverse effects ; Middle Aged ; Treatment Outcome ; },
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile (C. difficile) infection. The recommended treatment for primary C. difficile infection is antibiotics. We present a patient who requested FMT for primary C. difficile infection.

CASE PRESENTATION: A patient in her sixties developed primary C. difficile infection following antibiotic therapy atter surgery for small bowel volvulus. The patient refused antibiotic treatment and contacted a research group that had just concluded a randomised phase III trial assessing FMT for primary C. difficile infection. The trial had not yet been published, and FMT was not included in guideline recommendations for this indication. After joint decision-making involving the patient, her general practitioner, gastroenterologists and the research group, the patient received FMT and experienced complete remission of C. difficile symptoms within two days of treatment.

INTERPRETATION: This case illustrates how to evaluate experimental versus established treatments in light of new evidence and patient preferences that do not align with guideline recommendations.},
}

Humans
*Fecal Microbiota Transplantation
*Clostridium Infections/therapy
Female
Clostridioides difficile
Anti-Bacterial Agents/therapeutic use/adverse effects
Middle Aged
Treatment Outcome

@article {pmid41291207,
year = {2025},
author = {Li, C and Wang, H and Lin, X and Zeng, G and Li, X and Chen, W and Lu, H and Pan, J and Zhang, X and Rong, X and He, L and Peng, Y},
title = {Chronic alcohol consumption disrupts the integrity of the blood-brain barrier through the gut-brain axis.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-025-09235-w},
pmid = {41291207},
issn = {2399-3642},
abstract = {Chronic alcohol consumption can lead to disruption of the blood-brain barrier. The gut-brain axis may be involved in this pathological process. We investigated the gut microbiota of 30 healthy individuals and 30 alcohol use disorder (AUD) patients and found that at the genus level, AUD patients had decreased Faecalibacterium and increased Streptococcus. Liquid chromatography mass spectrometer (LC-MS/MS) revealed that 604 metabolites were upregulated and 606 were downregulated in AUD patients with cognitive impairment, compared to healthy controls. Chronic alcohol consumption led to cognitive decline in mice, with increased 20 kDa FITC-dextran leakage in the prefrontal cortex (PFC) and hippocampus, and decreased expression of ZO-1, occludin, and claudin-5. Transplantation of feces from AUD patients into germ-free mice resulted in increased 20 kDa FITC-dextran leakage in PFC and hippocampus, and decreased expression of ZO-1, occludin, and claudin-5, compared to mice receiving feces from healthy individuals. Administration of Faecalibacterium prausnitzii to chronically alcohol-fed mice improved cognitive function, reduced 20 kDa FITC-dextran leakage in PFC and hippocampus, and increased the expression of ZO-1, occludin, and claudin-5. Chronic alcohol consumption can disrupt the blood-brain barrier through the gut-brain axis. Faecalibacterium prausnitzii can improve alcohol-induced blood-brain barrier disruption and cognitive impairment.},
}

@article {pmid41290520,
year = {2025},
author = {Kumari, A and Priya, S and Barman, I and Dhasmana, A and Rustagi, S and Thapliyal, S and Deshwal, RK and Malik, S and Bora, J},
title = {Gut Microbiota Dynamics and Their Role in Pathogenesis and Management of Diabetes.},
journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica},
volume = {133},
number = {11},
pages = {e70090},
doi = {10.1111/apm.70090},
pmid = {41290520},
issn = {1600-0463},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/microbiology/therapy ; Dysbiosis/microbiology ; *Diabetes Mellitus, Type 1/microbiology/therapy ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; Prebiotics ; },
abstract = {The gut microbiota (GM) has emerged as an important element in the management of host metabolism, immune functions, and overall metabolic well-being. This review consolidates contemporary research regarding the intricate relationship between GM and diabetes mellitus, focusing on the mechanisms by which microbial composition and activity affect the development of both Type 1 (T1D) and Type 2 diabetes (T2D). Dysbiosis-characterized by diminished microbial diversity, a modified Firmicutes/Bacteroidetes ratio, and a reduction in advantageous SCFA-producing bacteria-has been significantly associated with disrupted glucose metabolism, insulin resistance, and persistent inflammation. Additionally, the review discusses the potential for microbial signatures and metabolites, such as SCFAs, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), to serve as novel biomarkers for early detection and risk evaluation. Moreover, it investigates therapeutic approaches designed to reestablish microbial balance through the use of probiotics, prebiotics, dietary changes, fecal microbiota transplantation (FMT), and microbiome engineering. By integrating findings from recent research, this paper emphasizes the groundbreaking possibilities of microbiome-centric diagnostics and treatments in individualized diabetes care.},
}

Humans
*Gastrointestinal Microbiome
*Diabetes Mellitus, Type 2/microbiology/therapy
Dysbiosis/microbiology
*Diabetes Mellitus, Type 1/microbiology/therapy
Fecal Microbiota Transplantation
Animals
Probiotics/therapeutic use
Prebiotics

@article {pmid41288714,
year = {2025},
author = {Quiroga-Centeno, AC and Atanasova, K and Ebert, MP and Thomann, AK and Reindl, W},
title = {Emerging microbiome-directed therapies in inflammatory bowel disease: beyond diet modification and FMT.},
journal = {Seminars in immunopathology},
volume = {47},
number = {1},
pages = {42},
pmid = {41288714},
issn = {1863-2300},
mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/etiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Animals ; Dysbiosis/therapy ; },
abstract = {Inflammatory bowel disease (IBD) is a multifactorial and heterogeneous disorder that remains challenging to manage. Growing evidence implicates the gut microbiome as a key player in IBD pathogenesis, with many patients displaying intestinal dysbiosis that can drive aberrant immune responses. Traditional microbiome-targeted interventions, such as dietary modifications, probiotics, and fecal microbiota transplantation (FMT), have yielded mixed and often temporary benefits in IBD. This shortcoming of broad-spectrum approaches underscores the need for more precise, personalized strategies that account for each patient's unique microbiota and disease phenotype. Recent advances in omics and bioengineering have catalyzed the development of emerging microbiome-directed therapies that move beyond these broad approaches. This narrative review highlights emerging microbiome-directed therapies that aim to restore gut homeostasis and mitigate inflammation in IBD. We critically evaluate the rationale and therapeutic potential of rationally designed bacterial consortia and genetically engineered bacteria, which represent next-generation probiotics tailored to complement deficient microbial functions or deliver anti-inflammatory agents in situ. We also expand the discussion to underexplored microbiome constituents - archaea, protists, bacteriophages, and fungi - highlighting their roles in IBD and potential as therapeutic targets. Finally, we discuss the key advances and ongoing challenges of these innovative approaches, from ecological stability and engraftment to safety and regulatory considerations.},
}

Humans
*Inflammatory Bowel Diseases/therapy/microbiology/etiology
*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome/immunology
Probiotics/therapeutic use
Animals
Dysbiosis/therapy

@article {pmid41287858,
year = {2025},
author = {Liu, N and Wang, DX and Hao, JX and Yan, XF and Lv, CL and Yan, JG and Liu, GF},
title = {Fecal Microbiota Transplantation Combined with Lifestyle Modification in the Management of Metabolic Dysfunction-Associated Fatty Liver Disease: Two Case Reports and Literature Review.},
journal = {Diabetes, metabolic syndrome and obesity : targets and therapy},
volume = {18},
number = {},
pages = {4299-4307},
pmid = {41287858},
issn = {1178-7007},
abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent condition, with gut microbiota dysbiosis playing a contributory role in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach for MAFLD. This report describes two patients diagnosed with MAFLD who underwent FMT in combination with lifestyle intervention. Post treatment findings demonstrated notable improvements in body mass index (decreased by 20.7% and 3%, respectively), serum transaminases levels (decreased by 51% and 27.2%, respectively), lipid profiles, uric acid concentrations, and liver stiffness measurements (decreased by 22.2% and 24.2%, respectively). Additionally, microbiome analysis showed increased diversity, improved anti-inflammatory and colonization resistance capacity, reduced pathogens, and enriched probiotics. A review of seven Chinese and international randomized controlled trials (RCTs) investigating the application of FMT in MAFLD was conducted. Among these, four trials reported improvement in liver function post-treatment. Two trials reported reductions in small intestinal or gastric permeability, one trial demonstrated a decrease in homeostasis model assessment of insulin resistance (HOMA-IR), one trial noted a reduction in blood lipid levels, and one trial documented a decrease in fat attenuation index (FAI). Only one trial included histological evaluation of liver tissue before and after FMT, which did not demonstrate significant pathological improvement. The combination of FMT and lifestyle intervention has achieved quite satisfactory therapeutic effects in the treatment of MAFLD, providing new ideas and potential therapeutic targets for the management of MAFLD. This approach holds broad application prospects. However, further confirmation through large-scale RCTs is still needed.},
}

@article {pmid41287633,
year = {2025},
author = {Marques, I and Marcos, P},
title = {Acute hepatic porphyrias.},
journal = {Porto biomedical journal},
volume = {10},
number = {6},
pages = {e308},
pmid = {41287633},
issn = {2444-8672},
abstract = {INTRODUCTION: Porphyrias are rare genetic disorders caused by heme biosynthesis pathway enzyme mutations, leading to porphyrin precursors build up in various tissues and diverse symptoms. This review centers on acute hepatic porphyrias (AHP).

METHODS: A MEDLINE through PubMed database literature review was conducted. Systematic reviews, clinical trials, cohort studies, case-control studies, expert reviews, and guidelines were preferred for analysis.

RESULTS: There are 4 types of AHP: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase deficiency porphyria. These conditions primarily present as neurovisceral attacks, characterized by severe abdominal pain, neuropsychiatric symptoms, or skin lesions, predominantly affecting women aged 15 to 50 years. The diagnostic methods include biochemical tests that assess urinary levels of aminolevulinic acid and porphobilinogen. In addition, measuring porphyrin levels in urine or feces can provide more insights into the type of AHP; however, a definitive diagnosis of the specific type is made through genetic testing. Treatment involves high-glucose diets, intravenous hemin for acute attacks, and givosiran for the prophylaxis of frequent attacks. Liver transplantation remains the only curative option. It is crucial to monitor chronic complications associated with hepatic porphyrias, particularly hepatocellular carcinoma, kidney disease, and arterial hypertension.

CONCLUSION: AHP continues to be an underrecognized condition, warranting consideration in individuals experiencing unexplained abdominal pain, neuropathy, psychiatric symptoms, or skin lesions. There is a need for improved diagnostic techniques and treatment options.},
}

@article {pmid41285255,
year = {2025},
author = {Wang, S and Ma, G and Qi, C and Cheng, S and Lai, H and Zhou, L and Wu, G and Chen, Z and Mao, X and Jing, T and He, Y and Zhou, H},
title = {Trimethylamine-N-oxide disrupts spermatogenesis by inducing mitochondrial oxidative stress injury through Hippo signaling.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2025.11.052},
pmid = {41285255},
issn = {1873-4596},
abstract = {BACKGROUND: The gut-testis axis is increasingly recognized as a regulator of male reproductive health; however, the key microbial contributors, metabolites, and underlying mechanisms remain unclear.

METHODS: We performed fecal metagenomic sequencing in 107 participants to identify microbial taxa associated with abnormal semen parameters. Serum trimethylamine-N-oxide (TMAO) levels were measured and correlated with semen quality. In mouse models, including fecal microbiota transplantation, dietary choline supplementation, mono-colonization, and direct TMAO administration, we assessed sperm morphology, testicular androgen synthesis, and testicular histology. Testicular transcriptomics, in vitro Leydig cell assays, and mitochondrial function analyses were conducted to investigate the effects of TMAO on Hippo signaling, oxidative phosphorylation, mitochondrial membrane damage, and steroidogenesis.

RESULTS: Choline-to-trimethylamine converting bacteria, including Phocaeicola massiliensis, Veillonella spp., and Klebsiella pneumoniae, were enriched in men with abnormal semen parameters. Circulating TMAO levels were inversely associated with semen volume, total sperm count, and motile sperm count. In mouse models, elevated TMAO induced testicular dysfunction characterized by impaired sperm morphology, reduced testicular androgen synthesis, and histological abnormalities. Consistently, gene set enrichment analysis (GSEA) of testicular transcriptomes revealed significant suppression of mitochondrial translation, membrane integrity, oxidative phosphorylation, and adenosine triphosphate (ATP) metabolism. TMAO also suppressed steroidogenesis by reducing the expression of steroidogenic acute regulatory protein (StAR). Mechanistic studies in TM3 Leydig cells further demonstrated that TMAO, by promoting Yap phosphorylation, disrupted mitochondrial structure and morphology, decreased mitochondrial membrane potential, increased mitochondrial reactive oxygen species (ROS) levels, impaired ATP synthesis, and promoted mitochondrial fragmentation with upregulation of the mitochondrial fission molecule (Fis1).

CONCLUSIONS: In conclusion, our findings demonstrate that TMAO activates Hippo signaling to induce mitochondrial dysfunction and suppress testosterone synthesis, thereby impairing spermatogenesis. These results highlight TMAO biosynthesis and its downstream signaling as potential therapeutic targets for improving male fertility.},
}

@article {pmid41284175,
year = {2025},
author = {Olesen, RH and Larsen, EB and Rubak, T and Baunwall, SMD and Paaske, SE and Gregersen, M and Erikstrup, C and Olsen, K and Dahlerup, JF and Kjaer, TK and Krogh, CB and Ehlers, LH and Hvas, CL},
title = {Increasing patient access to faecal microbiota transplantation with remote delivery: a cost analysis of outpatient versus home-based treatment.},
journal = {Health economics review},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13561-025-00706-8},
pmid = {41284175},
issn = {2191-1991},
support = {NNF22OC0074080//Novo Nordisk Foundation/ ; },
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) is used in less than 10% of the patients in Europe who meet the indication. Encapsulated FMT allows increased use for CDI because capsules can be safely shipped to local healthcare facilities and administered orally to patients without use of e.g. colonoscopy. The aim of this study was to calculate and compare the costs of alternative ways of delivering encapsulated FMT to patients with CDI in Denmark, including outpatient treatment at a specialised FMT centre, outpatient treatment at local hospitals including remote delivery to the Faroe Islands, and home-based care.

METHODS: Applying a healthcare perspective, we used an activity-based costing approach, combining data from a pragmatic clinical randomised trial with the best available literature and expert input. Only relevant costs were included. The main outcome was the average cost of delivering outpatient, encapsulated FMT treatment at an FMT centre, at a local hospital, or in the patient's home, only including additional costs related to delivery. An 8-week time horizon was applied for the analysis. Probabilistic and deterministic sensitivity analyses were applied to evaluate decision uncertainty and the robustness of the results.

RESULTS: In a pragmatic randomised trial including 217 patients with CDI, 135 patients received FMT. Analysing relevant costs in a base case analysis, local outpatient treatment (€145) was cost-saving compared with both treatment at the FMT centre (€209) and home-based treatment (€353). These differences remained robust across sensitivity analyses, including those accounting for patients' time costs. In the Faroe Islands case, shipment to remote locations added an average cost of €54 per FMT to the cost for the local outpatient treatment.

CONCLUSION: Capsule-based FMT treatment has made it clinically and economically feasible to administer FMT in contextual settings outside of specialised hospitals. Our findings highlight the importance of local hospital-based treatment for increasing patient access to FMT, the ability to ship FMT to remote locations lacking a FMT centre, and the option of home-based treatment for a selected group of patients who may not tolerate transport to hospital.},
}

@article {pmid41282240,
year = {2025},
author = {Gancz, A and Zhang, G and McMillan, A and Dougherty, M and McGill, S and Gulati, A and Baker, E and Theriot, C},
title = {Successful Fecal Microbiota Transplants in Post-antibiotic Treated Recurrent Clostridioides difficile Patients Induce Acylcarnitine and Sphingolipid Lipidomic Shifts.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7888346/v1},
pmid = {41282240},
issn = {2693-5015},
abstract = {Clostridioides difficile infection (CDI) is an urgent public health threat in the United States, resulting on an annual basis in over half a million cases, more than 29,000 deaths, and $4.8 billion in healthcare costs. While fecal microbiota transplants (FMTs) have proven more effective than standard-of-care antibiotics in resolving recurrent CDI (rCDI), their inherent risks underscore the need for advancements in regulated alternative therapies such as live biotherapeutic products (LBPs). The development of effective LBPs, however, is contingent upon better understanding the biological mechanisms underlying FMT efficacy. Building on our previously published untargeted metabolomic study which identified lipids as major explanatory factors associated with successful FMTs, we assessed additional lipid species using an instrumental platform coupling liquid chromatography, ion mobility spectrometry, collision induced dissociation, and mass spectrometry (LC-IMS-CID-MS) techniques. This platform and data analysis workflow enable the evaluation of >850 unique lipid species across 26 classes. Here, we confidently identified 397 lipids in the stools of 15 rCDI patients at pre- and post-FMT (2 week, 2 month, and 6 month) time points. Statistical evaluations of the lipidomic data illustrated that FMT-administration drastically reshapes the lipidome (adonis test, R [2] =0.11999, Pr(>F) <0.001), including 96 specific lipid species across 18 lipid classes (mixed effects modeling, BH correction, p < 0.05). In particular, we noted that medium and long-chain acylcarnitines decreased following FMT administration, while very long-chain acylcarnitines were elevated in post-FMT samples. Additionally, we observed assayed sphingolipids to be elevated pre-FMT with the exception of trihydroxy ceramides, which were highly upregulated post-FMT. These lipidomic alterations suggest that FMT administration may influence intestinal barrier integrity, inflammatory signaling, or apoptosis pathways. Interestingly, there was a strong co-occurrence of medium and long-chain acylcarnitines with Enterobacteriaceae, a bacterial family that has been demonstrated to utilize carnitine for growth. These findings highlight the critical role of the lipidome in patient susceptibility to rCDI and suggest the interactions between microbiota and lipids pre- and post-FMT as targets for developing next-generation LBPs.},
}

@article {pmid41282164,
year = {2025},
author = {Gavini, C and Raux, L and Labouèbe, G and Gornick, E and Hugh, SM and Elshareif, N and Calcutt, N and Summa, PD and Gorostidi, F and Vonaesch, P and Mansuy-Aubert, V},
title = {Dietary Fiber Improves Somatosensory Function in Western Diet-Fed Mice by Remodeling Adipose Immune Cells via FFAR2 Signaling.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7868021/v1},
pmid = {41282164},
issn = {2693-5015},
abstract = {Westernized diets (WDs)-high in fat and sugar and low in fiber-produce somatosensory deficits, chronic pain, and neuropathy, yet the mechanisms linking diet to peripheral nervous system (PNS) pathology remain incompletely defined. Emerging evidence implicates gut-derived metabolites in sensory homeostasis; for example, fecal microbiota transplantation (FMT) from lean donors to WD fed mice reduces hypersensitivity and attenuates PNS inflammation, although FMT outcomes are variable. We therefore tested whether targeted modulation of the gut microbiota with fermentable complex carbohydrates could reproducibly improve somatosensory function in WD-fed mice. Using an integrated pipeline-behavioral and physiological assays, peripheral nerve electrophysiology, and molecular and immune profiling-we show that short-chain fatty acids (SCFAs) generated by fermentation remodel adipose tissue depots and act via the SCFA receptor FFAR2 (GPR43) to ameliorate sensory deficits. These findings identify a microbiota-SCFA-FFAR2 axis that couples dietary fiber to PNS function and provide a tractable alternative to FMT for mitigating WD-associated sensory neuropathy.},
}

@article {pmid41282140,
year = {2025},
author = {Gascoigne, N and Wojciech, L and Prasad, M and Brzostek, J and Rybakin, V and Hoerter, J and Hou, B and Tung, D and Chua, YL and Ampudia, J and Rai, A and Chodaczek, G and Fu, G and Pettersson, S},
title = {The role of Themis in development of type 2 diabetes.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7943370/v1},
pmid = {41282140},
issn = {2693-5015},
abstract = {Type 2 diabetes (T2D) is a complex metabolic disorder driven by chronic inflammation and immune dysregulation, particularly within adipose tissue. This study investigates the role of the T cell-specific protein Themis in modulating immune-metabolic interactions that contribute to T2D pathogenesis. Using high-fat diet (HFD)-induced obesity models, we demonstrate that Themis -deficient (KO) mice exhibit accelerated weight gain, glucose intolerance, and insulin resistance compared to wild-type (WT) controls. These metabolic abnormalities are linked to functional alterations in the CD8[+] T cell compartment, including site-specific clonal expansion and reshaping of the T cell receptor (TCR) repertoire within adipose tissue, suggesting antigen-driven activation. Additionally, Themis deficiency leads to significant shifts in gut microbiome composition, characterized by reduced diversity and increased abundance of Firmicutes , particularly Clostridium species. However, fecal microbiota transplantation from Themis KO mice into germ-free WT hosts failed to recapitulate the full T2D phenotype, underscoring the dominant role of intrinsic immune dysfunction over microbial dysbiosis. These findings highlight a synergistic interplay between adaptive immunity and the microbiome in shaping metabolic outcomes and suggest that T cells play a central role in responses that influence T2D progression. Our data advocate for a more integrated approach to T2D research, incorporating genetic, immunological, and microbial factors.},
}

@article {pmid41281485,
year = {2025},
author = {Demirli Atici, S},
title = {Innovative insights into gut microbiota modulation in colorectal cancer: From microbial dysbiosis to therapeutic strategies.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {11},
pages = {108747},
pmid = {41281485},
issn = {1948-5204},
abstract = {Colorectal cancer (CRC) is increasingly recognized as a multifactorial disease influenced by hereditary, environmental, and microbial factors. This article explores recent insights into the role of gut microbiota dysbiosis in CRC pathogenesis and progression. Key differences in microbial composition, characterized by enrichment of pro-carcinogenic species such as Fusobacterium nucleatum and Bacteroides fragilis and depletion of beneficial commensals like Faecalibacterium prausnitzii, have been identified alongside changes in microbial metabolites such as short-chain fatty acids and secondary bile acids. We discuss immune system modulation by the microbiota, formation of bacterial biofilms, and the activation of host pathways such as the urea cycle during tumorigenesis. Special attention is given to therapeutic innovations, including microbiota-informed precision modelling, synthetic biology-based engineered probiotics, and evolving alternatives to fecal microbiota transplantation. These integrative strategies represent promising tools in the era of personalized oncology for CRC.},
}

@article {pmid41281468,
year = {2025},
author = {Rijkers, GT and Langcauon, Y and van Leersum, P and Popović, L and van Overveld, FJ},
title = {Role of microbiota in the outcome of immune checkpoint inhibition therapy of cancer.},
journal = {Exploration of targeted anti-tumor therapy},
volume = {6},
number = {},
pages = {1002348},
pmid = {41281468},
issn = {2692-3114},
abstract = {The realization that the composition and functionality of gut microbiota have an impact on the outcome of immune checkpoint inhibition (ICI) therapy of cancer has initiated research into the potential of microbiota management as adjunctive therapy. Fecal microbiota transplantation can improve the outcome of ICI, but for optimal donor selection, safety, and large-scale implementation, there remain bottlenecks. Alternative strategies, such as the use of selected bacterial species, require fundamental knowledge of the underlying mechanisms governing the interaction between (intestinal) microbiota and the immune system. Gut microbiota also appears to be able to colonize the tumor microenvironment. Some bacterial species directly or indirectly promote tumor growth. Other defined species have tumoricidal properties. These findings and insights are now being used to further optimize the functionality of the immune system and shape the tumor microenvironment in order to improve the outcome of ICI.},
}

@article {pmid41280983,
year = {2025},
author = {Nadeem, O and Imran, MS and Siddique, N},
title = {Recurrent Clostridium difficile Infections in a Patient With Ulcerative Colitis: A Case Report.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e95130},
pmid = {41280983},
issn = {2168-8184},
abstract = {Clostridium difficile infection (CDI) poses a substantial clinical challenge, especially in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). Patients with UC are at greater risk of CDI and tend to experience a more severe disease course and higher rates of recurrence than the general population. We report a case of an elderly man in his early 90s with a long-standing history of UC treated with mesalazine, who had a prior hospitalization for hyponatremia and a history of CDI. During his most recent four-month hospitalization, he developed three separate episodes of CDI, confirmed by stool PCR and toxin assays. Despite treatment with vancomycin, metronidazole, and fidaxomicin in succession, he experienced recurrent episodes of CDI that ultimately progressed to septic shock and death. This case highlights the nature of recurrent CDI in this patient population and the complexity and increased morbidity associated with its management in elderly patients with UC. It underscores the importance of careful evaluation of underlying risk factors, judicious antibiotic use, and consideration of alternative treatment modalities, such as faecal microbiota transplantation (FMT), for the prevention of recurrent CDI.},
}

@article {pmid41280921,
year = {2025},
author = {Li, X and Yuan, Q and Huang, H and Wang, L},
title = {Gut microbiota in irritable bowel syndrome: a narrative review of mechanisms and microbiome-based therapies.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1695321},
pmid = {41280921},
issn = {1664-3224},
mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Animals ; Prebiotics/administration & dosage ; },
abstract = {Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, and its pathogenesis remains unclear. Dysbiosis of the gut microbiota is associated with IBS. The gut microbiota may modulate IBS symptoms via the epithelial barrier, mucosal immunity, microbial metabolites (e.g., short-chain fatty acids and bile acids), and gut-brain signaling. Currently, dietary approaches, probiotics, prebiotics, rifaximin, and fecal microbiota transplantation show variable benefit; effects are strain-/context-dependent and evidence certainty varies, with adverse-event reporting inconsistent. This narrative review takes a subtype-aware, mechanism-first perspective to summarize microbiota functions, symptom links, and intervention evidence with safety considerations. This review offers new perspectives and insights for precision treatment and microbiome research in IBS.},
}

Humans
*Irritable Bowel Syndrome/therapy/microbiology/immunology
*Gastrointestinal Microbiome/immunology
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Dysbiosis/therapy
Animals
Prebiotics/administration & dosage

@article {pmid41280320,
year = {2025},
author = {Shackelford, BB and Kedir, K and Babiker, A and Sintayehu, B and Negash, AA and Abdissa, A and Taye, WA and Beyene, E and Woodworth, MH and Hennink, MM},
title = {Knowledge and Acceptability of Fecal Microbiota Transplantation Among Patients, Caregivers, and Health Care Providers in Ethiopia.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf676},
pmid = {41280320},
issn = {2328-8957},
abstract = {BACKGROUND: Malnutrition and antimicrobial-resistant infections are major causes of morbidity and mortality in low-income countries. These conditions have been associated with the gut microbiome, although little is known about the acceptability of microbiota therapies such as fecal microbiota transplantation (FMT). We explored the acceptability of FMT among health care providers (HCPs) and patients in Addis Ababa, Ethiopia.

METHODS: In this qualitative study, we purposively sampled patients with bacterial infections and acute malnutrition, caregivers, and HCPs at two hospitals. Eight focus group discussions were held. Amharic and English discussion guides covered knowledge of FMT and perceived barriers or facilitators for uptake. Data were transcribed and translated into English when necessary. MAXQDA software was used for a thematic analysis, with trained researchers closely reading transcripts to identify issues, develop a codebook, iteratively code data, and assess intercoder agreement. Description, comparison, and categorization were conducted to discern core themes, and validity checks ensured that findings were grounded in the data.

RESULTS: HCPs indicated a general willingness to prescribe FMT, provided that there was sufficient evidence supporting its efficacy and safety and they were confident on patient adherence. Patient acceptability of FMT was categorized along a continuum from those who were unconvinced, persuadable, amenable, and accepting of salvage treatment.

CONCLUSIONS: FMT may be acceptable for HCPs and patients in Addis Ababa, although interventions are needed to enhance acceptance among some groups, such as marketing it as standard medication, obtaining endorsement by religious leaders, providing multiple formulations, and/or providing thoughtful health communication.},
}

@article {pmid41280275,
year = {2026},
author = {Qi, X and Zhang, Y and Sun, Z and Wang, G and Ling, F},
title = {A simplified synthetic microbial community enhances resistance of crucian carp (Carassius auratus) to Aeromonas hydrophila infection through host immune activation.},
journal = {Synthetic and systems biotechnology},
volume = {11},
number = {},
pages = {407-418},
pmid = {41280275},
issn = {2405-805X},
abstract = {Bacterial diseases represent a major bottleneck in the sustainable development of aquaculture. The gut microbiota plays a vital role in host growth and health, including the enhancement of disease resistance. Although substantial progress has been made in elucidating the mechanisms of disease resistance in fish, the precise role of the gut microbiota in enhancing pathogen resistance in aquatic animals remains poorly understood. In this study, crucian carp (Carassius auratus) were used as a model to investigate the role of intestinal microbiota in modulating resistance to Aeromonas hydrophila. Individual crucian carp exhibited distinct clinical phenotypes following A. hydrophila infection. Specifically, significant differences were observed in the composition of the intestinal microbiota between fish displaying mild symptoms and those exhibiting severe phenotypic manifestations (α diversity: p < 0.01; β diversity: p = 0.001). Fecal microbiota transplantation (FMT) experiments demonstrated that fish with mild symptoms conferred enhanced resistance to A. hydrophila when their intestinal contents were transplanted into other individuals (p = 0.006). Further microbial analysis identified Cetobacterium (p = 0.013), Paraclostridium (p < 0.01), and Pseudomonas (p < 0.01) as key differential taxa. A simplified microbial community comprising these three strains was subsequently constructed. Feeding experiments confirmed that administration of this community significantly improved host resistance to A. hydrophila (p < 0.05) by activating intestinal immune responses and reinforcing the gut barrier. Overall, our findings underscore the potential of the microbial community as a novel strategy for disease prevention and control in aquaculture, providing a theoretical foundation for the development of microbiome-based therapies in fish health management.},
}

@article {pmid41278627,
year = {2025},
author = {Pandey, S and Abu, YF and Singh, P and Roy, S},
title = {Cross-Fostering with control dams rescues Gut Dysbiosis and Chromatin-associated Transcriptional Changes in Offspring of Opioid-Exposed Dams.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.07.687278},
pmid = {41278627},
issn = {2692-8205},
abstract = {Prenatal opioid exposure disrupts gut homeostasis and causes gastrointestinal complications in offspring, but the mechanisms remain unclear. Here using a murine model of prenatal hydromorphone exposure, we examined gut microbiota, intestinal injury, transcriptomic signatures, and chromatin accessibility. Exposed pups displayed marked dysbiosis, epithelial damage, and upregulation of inflammatory gene programs accompanied by relaxed ileal chromatin. Cross-fostering to opioid-naïve dams restored microbial diversity, reestablished metabolite-producing taxa, and reversed injury-associated transcriptional and chromatin changes. Fecal microbiota transplantation from exposed dams recapitulated intestinal injury, indicating a microbiome-driven mechanism. These findings reveal a novel gut-microbiome-epigenome axis underlying opioid-induced injury and highlight early microbial intervention as a potential strategy to mitigate developmental harm.},
}

@article {pmid41278477,
year = {2025},
author = {Chang, L and Liu, Y and Li, H and Yan, J and Wu, W and Chen, N and Ma, C and Zhao, X and Chen, J and Zhang, J},
title = {Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1717696},
pmid = {41278477},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Cirrhosis/microbiology/metabolism/pathology ; Dysbiosis/microbiology ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/metabolism ; Animals ; },
abstract = {Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid (SCFA)-producing taxa, particularly Lachnospiraceae and Ruminococcaceae. Meta-analyses indicate that fecal butyrate levels decrease by 40-70%, accompanied by a two- to fourfold increase in endotoxin concentrations. Bile acid profiling demonstrates an approximately 50% reduction in secondary bile acids and significant suppression of FXR/TGR5 signaling, whereas tryptophan metabolism shifts toward the kynurenine pathway, weakening epithelial defense and exacerbating portal hypertension. Clinically, dysbiosis and microbial translocation are associated with higher MELD scores, and patients in the lowest quartile of microbial diversity have a threefold increased risk of hepatic encephalopathy or spontaneous bacterial peritonitis. Microbiome-targeted interventions-including lactulose, rifaximin, probiotics or synbiotics, fecal microbiota transplantation, and bile acid modulators-restore community balance in 70-85% of clinical trials, although efficacy and safety vary by etiology and baseline microbiota composition. Integrated microbiome-metabolome models achieve areas under the curve (AUCs) of 0.82-0.90 for noninvasive classification and early detection of cirrhosis. Collectively, these findings underscore reproducible, quantitative microbiome-metabolite alterations and outline a roadmap for microbiome-informed precision care that connects mechanistic insight with clinical application, emphasizing the need for longitudinal and multi-ethnic validation.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Liver Cirrhosis/microbiology/metabolism/pathology
Dysbiosis/microbiology
Bile Acids and Salts/metabolism
Fatty Acids, Volatile/metabolism
Animals

@article {pmid41278154,
year = {2025},
author = {Zheng, L and Duan, SL and Wang, K},
title = {Research progress concerning the involvement of the intestinal microbiota in the occurrence and development of inflammatory bowel disease.},
journal = {World journal of gastroenterology},
volume = {31},
number = {42},
pages = {113170},
pmid = {41278154},
issn = {2219-2840},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/genetics ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Intestinal Mucosa/microbiology/immunology/pathology ; *Crohn Disease/microbiology/therapy/immunology ; *Colitis, Ulcerative/microbiology/therapy/immunology ; Genetic Predisposition to Disease ; Dysbiosis/microbiology/immunology/therapy ; *Inflammatory Bowel Diseases/microbiology/therapy ; Metagenomics ; Animals ; Metabolomics ; Immunity, Mucosal ; },
abstract = {Inflammatory bowel disease (IBD), a chronic disorder characterized by intestinal inflammation and mucosal damage, includes mainly Crohn's disease and ulcerative colitis. However, the cause of its onset remains unclear. The pathogenesis of IBD is closely related to host genetic susceptibility, disorders of the intestinal flora, damage to the intestinal mucosal barrier, and abnormal intestinal mucosal immunity. On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD, the influence of genetics on the intestinal barrier and intestinal microbiota; the metagenomics, metatranscriptomics, and metabolomics of the intestinal microbiota involved in IBD; and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.},
}

Humans
*Gastrointestinal Microbiome/immunology/genetics
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Intestinal Mucosa/microbiology/immunology/pathology
*Crohn Disease/microbiology/therapy/immunology
*Colitis, Ulcerative/microbiology/therapy/immunology
Genetic Predisposition to Disease
Dysbiosis/microbiology/immunology/therapy
*Inflammatory Bowel Diseases/microbiology/therapy
Metagenomics
Animals
Metabolomics
Immunity, Mucosal

@article {pmid41278045,
year = {2025},
author = {Hamza Saeed, M and Qamar, S and Ishtiaq, A and Umaira Khan, Q and Atta, A and Atta, M and Ishtiaq, H and Khan, M and Saeed, MR and Iqbal, A},
title = {Retraction: Fecal Microbiota Transplantation (FMT) in Clostridium difficile Infection: A Paradigm Shift in Gastrointestinal Microbiome Modulation.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {r206},
doi = {10.7759/cureus.r206},
pmid = {41278045},
issn = {2168-8184},
abstract = {[This retracts the article DOI: 10.7759/cureus.85054.].},
}

@article {pmid41277972,
year = {2025},
author = {Ye, N and Song, X and Yu, J and Bao, X and Ye, M and Jiang, L},
title = {Effects of gut microbiota interventions on patients with schizophrenia: a systematic review and meta-analysis.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1681559},
pmid = {41277972},
issn = {1664-302X},
abstract = {INTRODUCTION: Schizophrenia (SCH) is a chronic psychiatric disorder characterized by disturbances in thought, emotion, perception, and behavior. Although gut microbiota interventions (e.g., probiotics, prebiotics, synbiotics, dietary modifications and fecal microbiota transplantation) have been widely applied in the treatment of SCH, the most effective intervention strategy remains uncertain.

METHODS: By searching four databases, only randomized controlled trials (RCTs) were included to examine the impacts of gut microbiota interventions on SCH. The Cochrane risk-of-bias tool for randomized trials (RoB 2.0) was employed to assess the methodological quality of the included studies, RevMan5.4 was used for the meta-analysis, Stata 18 was used for sensitivity analysis, Engauge Digitizer was used to convert pictures to numbers and GRADEPro3.6 was used to grade the evidence quality.

RESULTS: This study incorporated RCTs published from the earliest records up to December 2024. A total of 10 RCTs, encompassing 585 participants, were analyzed. The meta-analysis demonstrated that interventions primarily utilizing probiotics to modulate gut microbiota significantly lowered the total Positive and Negative Syndrome Scale (PANSS) scores among patients (p = 0.001). Furthermore, substantial improvements were observed across multiple metabolic parameters: fasting blood sugar, triglycerides, total cholesterol, homeostasis model assessment of insulin resistance, and quantitative insulin sensitivity check index (all p < 0.05). While no significant effects were observed on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, and insulin.

CONCLUSION: This meta-analysis suggests that auxiliary probiotic interventions hold promise as an adjunctive therapy for schizophrenia, potentially yielding benefits in psychopathological, metabolic, and physiological domains. However, the current evidence remains inconclusive due to the limited number of studies, small sample sizes, and methodological variations. Firm therapeutic recommendations cannot be made at this time. The findings underscore the need for more robust, large-scale, and rigorously designed randomized controlled trials to definitively establish the efficacy and optimal protocols of auxiliary probiotic supplementation for SCH.

https://www.crd.york.ac.uk/PROSPERO, CRD 420250652507.},
}

@article {pmid41277959,
year = {2025},
author = {Zhang, S and Li, J and Li, L and Yuan, X},
title = {Gut microbiota on cardiovascular diseases-a mini review on current evidence.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1690411},
pmid = {41277959},
issn = {1664-302X},
abstract = {The gut microbiome has emerged as a critical modulator of cardiovascular disease (CVD) risk, offering a novel frontier for therapeutic intervention. This mini-review synthesizes current evidence on how probiotic-like bacteria and their metabolites mediate protective physiological mechanisms against CVD. Drawing from both animal models and human clinical trials, we elucidate the biological pathways, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acid metabolism, through which the gut microbiota influences hypertension, atherosclerosis, and heart failure. Furthermore, we examine microbiota-based strategies such as dietary modification, fecal microbiota transplantation (FMT), and pharmacological agents aimed at restoring microbial homeostasis. Despite promising mechanistic insights, human trials have yet to consistently demonstrate significant clinical benefits in reversing CVD outcomes via gut microbiota modulation. This review underscores the necessity of moving from correlation to causation, highlighting current limitations and future prospects for leveraging gut microbiome research in the development of personalized, effective therapeutic strategies for cardiovascular diseases.},
}

@article {pmid41277418,
year = {2025},
author = {Guggeis, MA and Andreani, NA and López-Agudelo, VA and Tran, F and Kadibalban, AS and Moors, KA and Marinos, G and Saboukh, A and Harris, D and Falk-Paulsen, M and Weber-Stiehl, S and Järke, L and Sommer, F and Welz, L and Bang, C and Franke, A and Chung, CJ and Bronowski, C and Schuchardt, S and Künzel, S and Aden, K and Schreiber, S and Kaleta, C and Baines, JF and Rosenstiel, P},
title = {Cross-species engraftment biases and metabolic divergence in gnotobiotic mice humanized with ulcerative colitis microbiota.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2581445},
doi = {10.1080/19490976.2025.2581445},
pmid = {41277418},
issn = {1949-0984},
mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice, Inbred C57BL ; Mice ; Bacteria/classification/genetics/isolation & purification/metabolism ; Disease Models, Animal ; Male ; Female ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/microbiology ; Fungi/classification/genetics/isolation & purification ; Middle Aged ; },
abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the human colon. Dysbiotic gut microbiota play a central role in its pathogenesis, and alterations in microbial composition and function are closely linked to disease activity. Humanized gnotobiotic mice are increasingly used to study how dysbiotic, human-derived microbial communities shape intestinal inflammation. However, the fidelity of microbiota engraftment and its impact on host physiology and metabolism remain incompletely understood. In this study, we performed a multiomics analysis following fecal microbiota transfer (FMT) from eight patients with active UC into germ-free C57BL/6N mice (five mice per donor). The mice were monitored over three weeks. Longitudinal analysis of microbial communities was performed using 16S rRNA (bacteria) and ITS2 (fungi) amplicon sequencing. Microbial metabolic flux was inferred via genome-scale metabolic modeling, and plasma metabolites were assessed by targeted metabolomics. We observed donor-specific physiological changes in recipient mice, including variations in body weight and adipose tissue. Spontaneous colonic inflammation occurred in one group and was subsequently linked to unintended transfer of Clostridioides difficile, which was previously clinically unrecognised in the donor. While bacterial engraftment overall was generally donor-specific and stable across mice, fungal taxa were transferred inconsistently and at low abundance. Despite similar overall plasma metabolomic profiles, select metabolites, including 3-indoleacetic acid, were differentially associated with specific microbial taxa. Moreover, metabolic modeling revealed disrupted metabolic exchange networks in the mouse microbiota compared to the original human donor communities. In conclusion, while human FMT into germ-free mice reliably transmits bacterial features, it introduces metabolic alterations and fails to fully reproduce the fungal microbiome. These findings underscore the need for cautious interpretation of microbiota-driven effects in gnotobiotic models and highlight the limitations of current approaches in replicating the full complexity of human gut ecosystems.},
}

Animals
Humans
*Gastrointestinal Microbiome
*Colitis, Ulcerative/microbiology/therapy/metabolism
*Fecal Microbiota Transplantation
Germ-Free Life
Mice, Inbred C57BL
Mice
Bacteria/classification/genetics/isolation & purification/metabolism
Disease Models, Animal
Male
Female
Feces/microbiology
RNA, Ribosomal, 16S/genetics
Dysbiosis/microbiology
Fungi/classification/genetics/isolation & purification
Middle Aged

@article {pmid41277357,
year = {2025},
author = {Zheng, X and Jiang, Y and Wang, W and Sun, K and Zhou, L and Zhang, Y and Cui, J and Yu, H and Dong, W and Yan, B},
title = {Asiatic Acid Alleviates Ulcerative Colitis Through a Gut Microbiota-Driven cAMP/PKA/NF-κB Pathway: γ-Glutamyltyrosine Is a Crucial Player.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70132},
pmid = {41277357},
issn = {1099-1573},
support = {82304807//National Natural Science Foundation of China/ ; BK20220299//Natural Science Foundation of Jiangsu Province/ ; Syhky202307//Clinical Pharmaceutical Research Foundation of Jiangsu Hengrui Medicine/ ; JLY2021052//Clinical Medical Science and Technology Development Foundation of Jiangsu University/ ; KS2203//Science and Technology Project of Kunshan/ ; KSF202139//Science and Technology Project of Kunshan/ ; },
abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica, has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.},
}

@article {pmid41276714,
year = {2025},
author = {Mustafa, MA and Vadia, N and Varma, P and Al-Shaker, H and Mohanty, B and Dhyani, A and Kaur, I and Chauhan, AS and Garg, G},
title = {The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {151},
pmid = {41276714},
issn = {1559-1182},
mesh = {*Alzheimer Disease/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain/metabolism/pathology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; },
abstract = {Microbiota residing in the human gastrointestinal tract play a critical role in maintaining homeostasis through immune regulation, metabolic activity, and signaling to the central nervous system. Recent studies have highlighted the influence of gut microbiota on neurodegenerative diseases, particularly Alzheimer's disease (AD), through the microbiota-gut-brain axis. This bidirectional communication system involves neural, hormonal, and immunological pathways, linking gut health directly with brain function. Disruption of the gut microbial balance-known as dysbiosis-has been associated with increased amyloid-beta (Aβ) deposition, tau hyperphosphorylation, oxidative stress, neuroinflammation, and impaired neurotransmission, all of which are key pathological features of AD. Microbial metabolites such as short-chain fatty acids, trimethylamine N-oxide, and gasotransmitters influence the permeability of the blood-brain barrier and modulate neuroimmune responses. Emerging evidence also indicates that gut microbiota may contribute to the early onset and progression of AD through systemic inflammation and metabolic dysfunction. Modulating the gut microbiome, therefore, presents a novel avenue for therapeutic intervention. This review aims to synthesize current findings on how gut microbiota alterations contribute to AD pathology. Furthermore, it explores therapeutic strategies-including diet, probiotics, prebiotics, polyphenols, and fecal microbiota transplantation-that hold potential in restoring microbial balance and mitigating cognitive decline in AD.},
}

*Alzheimer Disease/therapy/microbiology
Humans
*Gastrointestinal Microbiome/physiology
Animals
*Brain/metabolism/pathology
Dysbiosis
Probiotics/therapeutic use
*Brain-Gut Axis

@article {pmid40516101,
year = {2025},
author = {Saqr, A and Cheng, S and Al-Kofahi, M and Staley, C and Jacobson, PA},
title = {Microbiome-Informed Dosing: Exploring Gut Microbial Communities Impact on Mycophenolate Enterohepatic Circulation and Therapeutic Target Achievement.},
journal = {Clinical pharmacology and therapeutics},
volume = {118},
number = {6},
pages = {1477-1488},
doi = {10.1002/cpt.3740},
pmid = {40516101},
issn = {1532-6535},
mesh = {Humans ; *Mycophenolic Acid/pharmacokinetics/administration & dosage/analogs & derivatives ; *Gastrointestinal Microbiome/drug effects/physiology ; *Enterohepatic Circulation ; *Immunosuppressive Agents/pharmacokinetics/administration & dosage ; Male ; Female ; Middle Aged ; Hematopoietic Stem Cell Transplantation ; Adult ; Models, Biological ; Feces/microbiology ; },
abstract = {Pharmacomicrobiomics is an emerging field due to important microbiome effects on pharmacokinetics and clinical outcomes. However, the application of this knowledge remains limited. Mycophenolic acid (MPA) is the primary active metabolite of the immunosuppressant, mycophenolate mofetil (MMF). MPA undergoes glucuronidation to form MPA glucuronide (MPAG) which is deglucuronidated by bacterial β-glucuronidases and reformed as MPA through enterohepatic circulation (EHC). We studied the stool microbiome effect on the pharmacokinetics of MPA, its metabolites, and EHC in hematopoietic cell transplant (HCT) recipients using a semi-mechanistic population pharmacokinetic model. Microbiome communities were identified using correlation network analysis, and their impact on pharmacokinetics was assessed using full fixed-effects modeling. Simulations were then conducted to evaluate MMF dosing regimens and to assess the impact of community abundance on EHC and MPA therapeutic target achievement. High abundance of Bacteroides uniformis-dominant and Bacteroides vulgatus-dominant communities was associated with higher EHC and an increase in MPA exposure. Low abundance of these communities was associated with a 52-80% and 4-83% lower EHC and MPA exposure, respectively. Simulations showed 70% of individuals with low abundance of these communities achieved the therapeutic target at the typical HCT MMF dose of 1,000 mg Q8 hours IV; however, ≥ 95% were within the therapeutic target at 1,250 mg Q8 hours or 1,750 mg Q12 hours. EHC accounted for 34% of the MPA area under the curve. Elimination of EHC reduced troughs by 100%. This work quantifies the microbiome's effect on pharmacokinetics, paving the way for future microbiome-informed dosing to optimize therapeutic target attainment.},
}

Humans
*Mycophenolic Acid/pharmacokinetics/administration & dosage/analogs & derivatives
*Gastrointestinal Microbiome/drug effects/physiology
*Enterohepatic Circulation
*Immunosuppressive Agents/pharmacokinetics/administration & dosage
Male
Female
Middle Aged
Hematopoietic Stem Cell Transplantation
Adult
Models, Biological
Feces/microbiology

@article {pmid41276052,
year = {2025},
author = {Huan, P and Wang, W and Qi, Y and Sun, J and Zhou, R and Liu, L and Pan, S and Xu, Y and Wang, Z and Zhu, Z and Han, C},
title = {Cynomorium songaricum polysaccharide attenuates high-fat diet-induced testicular dysfunction by modulating the gut microbiota.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {149114},
doi = {10.1016/j.ijbiomac.2025.149114},
pmid = {41276052},
issn = {1879-0003},
abstract = {Obesity disrupts gut microbiota homeostasis and impairs spermatogenesis; however, microbiota-targeted therapies remain insufficiently explored. In this study, a water-soluble polysaccharide(CSP1) was purified from the medicinal plant Cynomorium songaricum. Structural characterization identified CSP1 as a homogeneous α-glucan (Mw 5776 Da) with a backbone of →4)-α-D-Glcp-(1 → residues and C-6 branching. In high-fat diet (HFD)-induced obese mice, CSP1 administration alleviated testicular dysfunction by enhancing sperm count and motility, restoring serum testosterone levels, and ameliorating histopathological damage and germ cell apoptosis. Mechanistically, CSP1 remodeled the gut microbiota composition by suppressing LPS-producing taxa while enriching beneficial populations including SCFA-producing Lachnospiraceae and Bacteroidota. This reshaping reinforced intestinal barrier integrity, as evidenced by the upregulation of ZO-1, occludin, and MUC2. Consequently, CSP1 treatment led to a favorable shift in gut microbiota-derived metabolites, significantly reducing systemic LPS translocation while increasing beneficial short-chain fatty acids (SCFAs) such as acetate and propionate. These changes collectively inhibited testicular TLR4/MyD88/NF-κB activation and downstream pro-inflammatory cytokines (TNF-α, IL-1β). Fecal microbiota transplantation confirmed the causal role of the gut microbiota in mediating CSP1's protective effects. Our findings establish CSP1 as a gut-microbiota-targeting polysaccharide that alleviates obesity-associated male infertility by orchestrating a beneficial remodeling of the gut microbial ecosystem and its metabolic output, offering a novel therapeutic strategy for metabolic reproductive disorders.},
}

@article {pmid41275982,
year = {2025},
author = {Huang, Y and Hu, J and Xu, H and Zhu, R and Liu, L and Chen, X and Sun, Y and Zhao, Y and Zhong, Y and Cheng, B and Huang, X and Lu, H and Xu, ZZ},
title = {Propylparaben Induces Immunotoxicity in Zebrafish via Oxidative Stress and Gut Microbiota-Immune Axis Dysregulation.},
journal = {Fish & shellfish immunology},
volume = {},
number = {},
pages = {111024},
doi = {10.1016/j.fsi.2025.111024},
pmid = {41275982},
issn = {1095-9947},
abstract = {Propylparaben (PP), a widely used preservative, has an unclear immunotoxicity profile. In this study, zebrafish embryos were exposed to 2.5, 5, and 10 μM PP to investigate its developmental and immunological effects. PP induced dose-dependent developmental abnormalities and immunotoxicity. Specifically, it significantly reduced the populations of neutrophils, macrophages, and hematopoietic stem cells (HSCs) in zebrafish embryos. Mechanistically, PP suppressed the TLR4/MyD88/NF-κB pathway and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in embryos, whereas adult zebrafish exhibited marked upregulation of this pathway and these cytokines in intestinal and splenic tissues. PP exposure also elevated reactive oxygen species (ROS) and lipid peroxidation. Co-treatment with the antioxidant astaxanthin (AST) attenuated PP-induced immunotoxicity by reducing ROS level and restoring HSCs, neutrophil, and macrophage populations, confirming oxidative stress as a key mechanism. Furthermore, PP induced gut microbiota dysbiosis and intestinal developmental defects. Exposing germ-free (GF) zebrafish embryos to PP resulted in no significant changes in neutrophils and HSCs, indicating that its immunotoxicity is microbiota-dependent. This was confirmed by fecal microbiota transplantation (FMT), where embryos receiving microbiota from PP-treated donors showed concentration-dependent decreases in neutrophils and HSCs. Our study elucidates the ecological and health risks of PP, advocating for reevaluation of preservative safety and microbiota-targeted mitigation strategies.},
}

@article {pmid41274019,
year = {2025},
author = {Chen, R and Qian, J and Wang, Q and Li, Y and Xu, Z and Zhang, M and Wang, M and Nie, H and Yang, W and Tong, X and Yan, F},
title = {Periodontitis exacerbates metabolic dysfunction-associated steatotic liver disease via the gut microbiota-derived tryptophan metabolism-AHR axis in obesity.},
journal = {EBioMedicine},
volume = {122},
number = {},
pages = {106037},
doi = {10.1016/j.ebiom.2025.106037},
pmid = {41274019},
issn = {2352-3964},
abstract = {BACKGROUND: Periodontitis is linked to metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms remain unclear.

METHODS: Periodontitis was investigated in male mice with high-fat diet (HFD)-induced MASLD. Gut microbiome and metabolomic profiling were conducted using16S rRNA gene sequencing, along with both untargeted and targeted metabolomic profiling via liquid chromatography-tandem mass spectrometry. Intestinal barrier integrity was evaluated by histopathological analysis. Faecal microbiota transplantation was conducted and the vital role of the aryl hydrocarbon receptor (AHR) was confirmed using Ahr gene knockout (Ahr[-/-]) mice. The protective roles of tryptophan derivative indole-3-propionic acid (IPA) and the tryptophan-metabolising probiotic Limosilactobacillus reuteri were assessed following their administration via oral gavage. The impact of endotoxin-mediated hyperinflammation on hepatic mitochondrial dynamics was examined in vitro.

FINDINGS: Periodontitis promoted MASLD, gut microbiota dysbiosis, and tryptophan metabolism depletion, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin overexpression in HFD-fed mice. Periodontitis-accelerated MASLD was attenuated in HFD-fed Ahr[-/-] mice. In an AHR-dependent manner, IPA or L. reuteri alleviated the detrimental effects of periodontitis on MASLD progression, intestinal barrier impairment, systemic inflammation, and endotoxin translocation to the liver. Conditioned medium from endotoxin-stimulated THP-1 cells promoted mitochondrial fission in HepG2 cells by upregulating Drp1 expression.

INTERPRETATION: Periodontitis exacerbates MASLD by disrupting the gut microbiota-tryptophan metabolism-AHR axis, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin translocation. Endotoxin plays a pivotal role in promoting hepatic mitochondrial fission during the exacerbation of MASLD by periodontitis. AHR agonists offer a novel intervention strategy for patients with comorbid MASLD and periodontitis.

FUNDING: This work was supported by the Jiangsu Province Key Research and Development Program [No. BE2022670]; National Natural Science Foundation of China [No. 82270979]; Jiangsu Provincial Medical Key Discipline Cultivation Unit [No. JSDW202246]; and High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University [No. 0224C001].},
}

@article {pmid41273871,
year = {2025},
author = {Jie, L and Liu, J and Liu, Y and Zhang, K and Shen, X and Xu, B and Ji, W and Shi, X},
title = {Sclareol alleviates synovial inflammation in knee osteoarthritis by regulating sphingolipid metabolism along the gut-bone axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157563},
doi = {10.1016/j.phymed.2025.157563},
pmid = {41273871},
issn = {1618-095X},
abstract = {OBJECTIVE: Sclareol(SCL) is a diterpene alcohol compound with anti-inflammatory, antibacterial, and antioxidant properties, and it has high oral bioavailability. However, its pharmacological effects in the field of knee osteoarthritis(KOA) remain unclear.

METHODS: The pharmacological effects of SCL intervention on synovial inflammation in KOA rats were observed using methods such as histopathology and molecular biology. Subsequently, further in vivo and in vitro experiments were conducted to explore the effects of SCL. By combining metabolomics and 16S rRNA sequencing, the impact of SCL on the gut microbiota and metabolic levels was investigated. Based on the results of the omics analyses, the mechanism by which SCL alleviates synovial inflammation in KOA was verified.

RESULTS: Histopathology and molecular biology showed that SCL can significantly improve synovial inflammation and pathological progression in KOA. However, SCL did not exhibit anti-inflammatory effects in vitro experiments or in rats treated with antibiotics. Combined analysis of untargeted metabolomics and 16S RNA-seq indicated that SCL may exert its effects by altering the abundance of bacterial groups like Prevotellaceae ga6a1 group and Corynebacterium and regulating the levels of lipid metabolites such as ceramides. Finally, our combined in vivo and in vitro experiments confirmed that fecal microbiota transplantation (FMT) from SCL-treated rats could modulate gut microbiota composition, reduce sphingolipid metabolism, lower necroptosis levels of synovial macrophages, and decrease inflammation in KOA rats.

CONCLUSION: SCL reduces the abundance of Prevotellaceae ga6a1 group and Corynebacterium decreased levels of ceramides, sphingomyelin, and sphingosine, which in turn lower synovial macrophage necroptosis and synovial inflammation.},
}

@article {pmid41271774,
year = {2025},
author = {Qin, W and Mei, Q and Wang, G and Wang, R and Huang, Z and Fu, Y and Xu, B and Huang, C and Ai, L and Zeng, Y},
title = {Faecalibacterium prausnitzii alleviates experimental recurrent acute pancreatitis by producing oleic acid to regulate MAPK/NF-κB signaling and Th17/Treg balance.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-025-00845-0},
pmid = {41271774},
issn = {2055-5008},
support = {No.82200714//National Natural Science Foundation--Youth Foundation/ ; No. 82300731//National Natural Science Foundation--Youth Foundation/ ; No.10-21-308-420//USST Medical-engineering Cross-project/ ; No. 32025029//National Science Foundation for Distinguished Young Scholars of China/ ; No. 82270671//Natural Science Foundation of China/ ; CCTR-2022B02//Shanghai General Hospital Characteristic Research Program/ ; },
abstract = {Acute pancreatitis (AP) is a complex gastrointestinal disorder associated with disruptions in the gut microbiome. However, the gut microbial and metabolomic profiles in recurrent acute pancreatitis (RAP), which is a clinically distinct subtype of AP, remain unclear. This study integrated microbiome-metabolome analysis to identify the key gut microbial species and metabolic pathways associated with RAP. The findings reveal that the abundance of Faecalibacterium prausnitzii (Fp) is significantly diminished in RAP patients, exhibiting a strong negative correlation with disease severity. Consistent with this observation, fecal microbiota transplantation enriched with Fp significantly ameliorated pancreatic injury in RAP mice. We further isolated Fp Ai 3-16 strain from the stool of healthy volunteers. Functional validation using experimental AP models demonstrates that Fp Ai 3-16 and its metabolite oleic acid (OA) can effectively attenuate pancreatitis by modulating MAPK/NF-κB signaling pathways and restoring the intestinal Th17/Treg balance. Importantly, these results extend beyond the context of RAP, as they highlight the broader significance of the gut-pancreas axis in the pathogenesis of AP. Thus, the elucidation of the underlying molecular mechanisms offers novel therapeutic avenues for RAP management and provides a foundation for further investigations into the intricate interplay between the gut microbiome and the pancreas.},
}

@article {pmid41270737,
year = {2025},
author = {Long, X and Wang, H and Lu, Y and Gao, X and Xiao, Y and Zhang, M and Guo, J and Yang, J and Zhang, R and Li, Q and Zhou, G and Yang, R and Chen, F and Wu, Q and Sun, L and Chu, C and Zhu, X and Wu, Z and Ren, Q and You, C and Liu, Z and Li, Q and Liu, D and Cheng, D and Kang, P and Chen, A and Wu, Q and Fang, Q and Wei, L and Zhang, L and Li, J and Panagiotou, G and Jia, W and Zeng, R and Ni, Y and Chen, L and Li, H},
title = {Interindividual variability in gut microbiome mediates the efficacy of resistant starch on MASLD.},
journal = {Cell metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmet.2025.10.017},
pmid = {41270737},
issn = {1932-7420},
abstract = {Our randomized, placebo-controlled trial showed resistant starch (RS), a type of prebiotic, has therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we observed its heterogeneous efficacy, where 30% of participants exhibited limited benefits, which was replicated in a multi-center trial (ChiCTR2300074588). Multi-omics analysis and fecal microbiota transplantation identified baseline microbiota as a dominant contributor of response. Further population stratification and network analysis combined with in vitro and in vivo experiments revealed Prevotella as the key cause of low response by inhibiting RS-degrading bacteria, thereby impairing RS utilization. Conversely, Bifidobacterium pseudocatenulatum RRP01, a strain isolated from our cohort, restored RS degradation and improved Prevotella-attenuated RS response. Furthermore, we developed a predictive model integrating baseline microbial and clinical features (area under the curve [AUC] = 0.74-0.87), enabling stratification for personalized interventions. Our study indicates that gut microbiota determines the heterogeneity in RS efficacy and offers possibilities for novel microbiota-oriented precision therapeutics for MASLD.},
}

@article {pmid41270390,
year = {2025},
author = {Chen, L and He, W and Gao, L and Lu, Y and Zhu, L},
title = {Shouhui Tongbian Capsules ameliorate heart failure and atrial fibrillation via gut microbiota regulation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157549},
doi = {10.1016/j.phymed.2025.157549},
pmid = {41270390},
issn = {1618-095X},
abstract = {BACKGROUND: Heart failure (HF) with atrial fibrillation (AF) poses a significant therapeutic challenge due to its complex pathophysiology. Shouhui Tongbian Capsules (SHTB) contain multiple active components that have been proven to affect HF or AF through the intestinal flora. However, the specific therapeutic effects of this drug on HF combined with AF, as well as whether these effects are achieved by regulating the intestinal flora, still require systematic research.

PURPOSE: This study aimed to elucidate the cardioprotective effects of SHTB in a doxorubicin (DOX)-induced HF/AF rat model, focusing on gut microbiota modulation and myocardial transcriptome regulation.

METHODS: Rats were randomized into control, model (DOX-induced HF/AF), SHTB treatment (low/medium/high doses), and metoprolol groups. Pharmacodynamically, cardiac function was assessed via echocardiography and electrocardiography. And myocardial fibrosis was quantitatively evaluated using pathomorphology analysis. Mechanistically, microvascular integrity was examined via immunofluorescence, while the neural activity ligand-receptor interaction pathway-related protein expression was analyzed by immunohistochemistry. Additionally, gut microbiota composition was determined via 16S rRNA sequencing, and myocardial transcriptome profiling was performed using RNA sequencing. Furthermore, fecal microbiota transplantation (FMT) experiments were performed to validate the role of gut microbiota in the observed effects.

RESULTS: The SHTB intervention significantly improved the cardiac function and electrophysiological stability of HF/AF rats, along with enhancing microvascular maturation and reducing myocardial fibrosis. The analysis of the intestinal microbiota showed that SHTB effectively restored the microbial ecological balance, especially regulating the abundance of key genera (such as Turicibacter) closely related to disease progression and treatment efficacy. Transcriptional analysis identified the neural activity ligand-receptor pathway as the key mechanism, and FMT experiments demonstrated that SHTB modulates the Edn1-Agtr1a-Bdkrb2 axis through gut microbiota, ultimately leading to improved cardiac function. The synergistic effect of the composition of the intestinal microbiota and myocardial molecular targets jointly contributed to the improvement of cardiac remodeling in HF/AF.

CONCLUSION: SHTB ameliorates HF with AF by synergistically modulating the gut-heart axis, involving gut microbiota restoration, myocardial fibrosis suppression, and vascular tension regulation via the Edn1-Agtr1a-Bdkrb2 axis. This multi-target mechanism substantiates SHTB's potential as a promising adjunct therapy for HF/AF.},
}

@article {pmid41270389,
year = {2025},
author = {Zheng, M and Meng, Y and Feng, J and Liang, H and Mu, X and Feng, C},
title = {Shenling Baizhu Powder potentiates immunotherapy response: putative roles of gut microbial remodeling and fatty acid metabolism modulation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {149},
number = {},
pages = {157559},
doi = {10.1016/j.phymed.2025.157559},
pmid = {41270389},
issn = {1618-095X},
abstract = {BACKGROUND: Low response rates and immune-related adverse events (irAEs) are major factors affecting the efficacy of PD-1 monoclonal antibody (mAb) immunotherapy in NSCLC. Modulating the gut microbiota-immune-tumor axis is considered a key strategy to overcome these challenges.

PURPOSE: This study aimed to investigate whether Shenling Baizhu powder (SLBZS), a traditional Chinese medicine formula, could enhance the efficacy of PD-1 mAb immunotherapy and mitigate irAEs by regulating gut microbiota and host metabolism.

STUDY DESIGN: Two experimental models were employed: (1) a standard Lewis subcutaneous tumor mouse model to evaluate therapeutic effects and irAEs, and (2) a lung metastasis model using bioluminescence imaging to assess tumor progression. Additionally, an antibiotic-cleared mouse model combined with fecal microbiota transplantation (FMT) was used to validate gut microbiota-mediated mechanisms.

METHODS: Subcutaneous tumor growth, organ toxicity, and metastasis were monitored in vivo. Multi-omics approaches included fecal 16S rDNA sequencing, untargeted/targeted plasma metabolomics, and immune profiling of splenic and tumor microenvironment (TME) lymphocytes. SLBZS/FMT interventions were applied to antibiotic-treated mice to assess microbiota-dependent effects.

RESULTS: SLBZS synergized with PD-1 mAb to significantly inhibit tumor growth and reduce multi-organ irAEs. In the metastasis model, SLBZS suppressed early tumor implantation and late-stage dissemination. Multi-omics analyses revealed that SLBZS enriched beneficial gut bacteria (e.g., Akkermansia, Lactobacillus, Muribaculum) and microbial metabolites, including short-chain fatty acids (SCFAs), while enhancing anti-tumor T-cell subsets in the spleen and TME. Critically, SLBZS/FMT restored gut microbiota homeostasis and reversed antibiotic-induced immunotherapy resistance.

CONCLUSION: SLBZS, as a traditional Chinese medicinal formulation, enhances the efficacy of PD-1 mAb through a unique dual-regulatory mechanism. It concurrently remodels the gut microbiota structure and optimizes the metabolic microenvironment, with these synergistic actions collectively amplifying anti-tumor immunity while reducing irAEs. This dual-mode efficacy distinguishes SLBZS from conventional microbial modulators that solely target microbiota without metabolic coordination. Our study provides the first experimental validation of SLBZS as a clinically valuable adjuvant of Chinese medicinal origin for NSCLC immunotherapy. Furthermore, we pioneer a novel research paradigm integrating traditional Chinese medical theory with the "microbiota-metabolism-immune network" axis, thereby offering innovative therapeutic strategies for refining cancer immunotherapies.},
}

@article {pmid41270175,
year = {2025},
author = {Liu, W and Yang, J and Wei, Z and Kong, W and Dong, Z and Wei, Y and Zhuang, J and Qi, J},
title = {miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease.},
journal = {Science advances},
volume = {11},
number = {47},
pages = {eadw5984},
doi = {10.1126/sciadv.adw5984},
pmid = {41270175},
issn = {2375-2548},
mesh = {*MicroRNAs/genetics/chemistry/administration & dosage ; *Nanoparticles/chemistry ; Animals ; *Inflammatory Bowel Diseases/microbiology/therapy/pathology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; Lacticaseibacillus rhamnosus/metabolism/genetics ; Extracellular Vesicles/metabolism ; *Biomimetic Materials/chemistry ; Disease Models, Animal ; Humans ; Colitis/pathology ; Biomimetics ; Probiotics ; },
abstract = {Modulation of gut microbiota has emerged as a promising therapeutic strategy for inflammatory bowel disease (IBD). However, current interventions such as probiotics and fecal microbiota transplantation remain limited by insufficient safety and efficacy. To address this, we engineered commensal Lactobacillus rhamnosus (LGG) using miRNA-loaded biomimetic nanoparticles to enhance its proliferation and indole-3-carboxaldehyde production. By functionalizing bacterial extracellular vesicles (BEVs) derived from LGG with lipid nanoparticles (LNPs), we developed BEV-LNPs that exhibited enhanced targeting efficiency toward LGG compared to Escherichia coli. In vitro and in vivo studies demonstrated that BEV-LNPs showed superior stability in simulated physiological fluids and gastrointestinal environments compared to conventional LNPs. When combined with 5-aminosalicylic acid, the BEV-LNP formulation notably improved outcomes in acute and chronic colitis models, reducing inflammation, restoring epithelial barrier integrity, and promoting microbial balance. This study presents an effective strategy for colitis treatment by leveraging miRNA-loaded nanoparticles.},
}

*MicroRNAs/genetics/chemistry/administration & dosage
*Nanoparticles/chemistry
Animals
*Inflammatory Bowel Diseases/microbiology/therapy/pathology/drug therapy
*Gastrointestinal Microbiome/drug effects
Mice
Lacticaseibacillus rhamnosus/metabolism/genetics
Extracellular Vesicles/metabolism
*Biomimetic Materials/chemistry
Disease Models, Animal
Humans
Colitis/pathology
Biomimetics
Probiotics

@article {pmid41269489,
year = {2025},
author = {Lapauw, L and Amini, N and Switsers, E and Dupont, J and Vercauteren, L and Derrien, M and Raes, J and Gielen, E},
title = {Effect of host and gut microbiota-altering interventions on sarcopenia or its defining parameters: a systematic review and meta-analysis of nutrition-based intervention studies.},
journal = {Aging clinical and experimental research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40520-025-03216-z},
pmid = {41269489},
issn = {1720-8319},
abstract = {AIM: To investigate effects of host- and gut microbiota (GM)-altering interventions on sarcopenia (parameters).

METHODS: Upon PROSPERO registration (CRD42022347363), six databases and one registry were searched until January 5th 2024 and updated on June 10th 2025 for diet, pre-, pro-, or synbiotics mono-interventions in populations with mean age ≥ 50 years. (Standardized) mean differences (SMD) and 95% confidence intervals (CI) were computed using random-effects models if heterogeneity was > 50%. Risk of bias (Rob) & GRADE assessments were carried out to assess the evidence' quality and certainty.

RESULTS: The qualitative analysis included 38 diet, 13 prebiotics, 11 probiotics and 1 synbiotics studies, totaling 4842 participants (59%♀), mostly of high RoB. The quantitative analysis included 49 studies. Probiotics improved muscle strength by 1.90 kg and gait speed by 0.08 m/s. Fiber (whole-food)-enriched diets improved muscle strength with 1.25 kg and energy-restricted diets, aimed at weight loss, improved muscle mass if mean age was < 60 years and if the intervention lasted no longer than 12 weeks. High-protein diets improved muscle mass in women and if the intervention lasted at least 12 weeks. Studies involving participants with sarcopenia were only included in the qualitative analysis, since none provided sufficient data to allow a quantitative synthesis.

DISCUSSION: Fiber (whole food)-enriched diets and probiotics improve muscle strength. The latter intervention also improves gait speed. High-protein diets improve muscle mass in women and with intervention durations ≥ 12 weeks. Future studies should include fecal sampling to assess whether GM modulate the observed effects.

CONCLUSION: Specific diets and probiotics offer potential to improve sarcopenia parameters.},
}

@article {pmid41269457,
year = {2025},
author = {Younis, NK and Alfarttoosi, KH and Sanghvi, G and Roopashree, R and Kashyap, A and Krithiga, T and Taher, WM and Alwan, M and Jawad, MJ and Ali Al-Nuaimi, AM},
title = {Attenuating Neurotoxicity Through Fecal Microbiota Transplant: Mechanisms and Therapeutic Potential.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {128},
pmid = {41269457},
issn = {1559-1182},
mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Neurotoxicity Syndromes/therapy/microbiology ; },
abstract = {Neurotoxicity, triggered by drugs, environmental pollutants, metabolic disorders, or infections, can cause lasting neurological dysfunction and cognitive impairment. Recent research highlights the gut microbiota's crucial role in regulating brain health and vulnerability to neurotoxic damage, sparking interest in fecal microbiota transplantation (FMT) as a potential treatment. This review examines how FMT may counteract neurotoxicity and assesses its therapeutic potential for neurodegenerative diseases, neuroinflammation, and cognitive decline. The gut-brain axis-a bidirectional communication system between the gut and the central nervous system (CNS)-acts as the primary route through which gut microbes influence brain function. Growing evidence suggests that microbiota imbalances can exacerbate neuroinflammation, oxidative stress, blood-brain barrier disruption, and altered neurotransmitter production, all of which contribute to neurotoxicity. FMT, the transfer of donor fecal microbes to a recipient's gut, has demonstrated promise in restoring microbial equilibrium and reducing neurotoxic effects in both animal studies and human trials. The review also explores microbial profiles tied to neuroprotection versus those linked to neurotoxic conditions, along with the prospects of tailored microbiome therapies. Despite its potential, FMT faces challenges, including protocol standardization, donor selection criteria, and long-term efficacy. More research is needed to unravel the intricacies of gut-brain interactions and optimize FMT for clinical use. If these hurdles are addressed, FMT could become a transformative therapy for neurotoxicity-related disorders.},
}

*Fecal Microbiota Transplantation/methods
Humans
Animals
*Gastrointestinal Microbiome/physiology
*Neurotoxicity Syndromes/therapy/microbiology

@article {pmid41268538,
year = {2025},
author = {Jiao, JM and Liu, CG and Zang, D and Chen, J},
title = {Gut microbiota and metabolites: emerging prospects in the treatment of non-small cell lung cancer.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1638942},
pmid = {41268538},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Carcinoma, Non-Small-Cell Lung/therapy/metabolism/microbiology ; *Lung Neoplasms/therapy/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; },
abstract = {Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of all cases, and is associated with a poor prognosis. Despite significant advancements in treatment modalities, therapeutic efficacy remains suboptimal, underscoring the urgent need for novel strategies. In recent years, increasing attention has been directed toward the pivotal role of gut microbiota-host interactions in the treatment of NSCLC. This review systematically examines the influence of current NSCLC therapies on gut microbiota and metabolism, explores the relationship between the microbiome and therapeutic response, and highlights the critical functions of probiotics, microbial metabolites, fecal microbiota transplantation (FMT), and dietary interventions in NSCLC management. By elucidating the mechanisms through which gut microbiota and their metabolites modulate treatment efficacy, we investigate the potential of exogenous interventions targeting the gut ecosystem to enhance therapeutic outcomes and mitigate adverse effects. Modulating the intestinal microbiota represents a promising clinical avenue and offers a new frontier for the development of future NSCLC treatment strategies.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*Carcinoma, Non-Small-Cell Lung/therapy/metabolism/microbiology
*Lung Neoplasms/therapy/metabolism/microbiology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Animals

@article {pmid41268164,
year = {2025},
author = {Zhao, M and Chen, D and Hu, X and Xie, C and Xu, L and Zhou, F},
title = {Gut-ovary axis in polycystic ovary syndrome: mechanistic insights and gut microbiota-targeted therapeutic strategies.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1684492},
pmid = {41268164},
issn = {1664-2392},
mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/therapy/metabolism ; *Gastrointestinal Microbiome/physiology ; Female ; Probiotics/therapeutic use ; *Ovary/metabolism ; Fecal Microbiota Transplantation/methods ; },
abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that significantly affects women's reproductive health and quality of life. Its pathogenesis involves multiple factors, including genetics, environment, and metabolism. In recent years, with the growing body of research on PCOS, the "gut-ovary axis" hypothesis has become a prominent research focus. This hypothesis suggests that an imbalance in gut bacteria may significantly influence the onset and progression of PCOS through various pathways, such as immune regulation, metabolic disturbances, and hormonal imbalances. This article aims to review the role of the "gut-ovary axis" in PCOS and to explore novel treatment strategies based on gut microbiota modulation, including probiotics, fecal microbiota transplantation, and dietary interventions. These strategies represent promising research avenues for future PCOS treatments, with preliminary studies demonstrating their potential to improve clinical symptoms. However, it is crucial to note that these are not yet established therapies and require substantial further validation. Novelty and Significance of this Review: This review moves beyond a descriptive catalog of associations to provide a critical appraisal of the gut-ovary axis in PCOS. We systematically differentiate well-established mechanisms from speculative hypotheses, explicitly identify persistent knowledge gaps, and evaluate the translational potential of microbiota-targeted therapies, thereby offering a refined framework for future basic and clinical research.},
}

Humans
*Polycystic Ovary Syndrome/microbiology/therapy/metabolism
*Gastrointestinal Microbiome/physiology
Female
Probiotics/therapeutic use
*Ovary/metabolism
Fecal Microbiota Transplantation/methods

@article {pmid41267780,
year = {2025},
author = {Sharma, I and Sudarsanan, D and Moonah, S},
title = {The gut microbiome as a major source of drug-resistant infections: emerging strategies to decolonize and target the gut reservoir.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1692582},
pmid = {41267780},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Bacterial Infections/microbiology/therapy/prevention & control ; *Drug Resistance, Bacterial ; Phage Therapy ; *Bacteria/drug effects ; Antimicrobial Peptides/therapeutic use ; },
abstract = {Infections caused by antimicrobial-resistant bacteria represent a significant global health crisis that continues to worsen, creating an urgent need for alternative treatment and prevention strategies. A major source of drug-resistant bacteria is the human gut. The gut microbiota consists of bacteria that are frequently exposed to antibiotics, leading to selective pressure that promotes the development of resistant strains such as carbapenem-resistant Enterobacterales (CRE) and vancomycin-resistant enterococci (VRE). These drug-resistant bacteria can spread from the gut to other body sites, leading to hard-to-treat and potentially life-threatening infections such as bacteremia, surgical site infections, and urinary tract infections. Targeting the gut reservoir is essential in the fight against antimicrobial resistance. In this review, we focus on emerging non-antibiotic strategies aimed at eliminating drug resistant bacteria from the gut before they cause invasive infections, with particular emphasis on clinical evidence. Approaches discussed include fecal microbiota transplantation, bacteriophage therapy, antimicrobial peptides, probiotics, and dietary interventions. Optimizing these strategies, while continuing to explore newer approaches, will be essential to combat the growing threat of drug-resistant infections.},
}

Humans
*Gastrointestinal Microbiome/drug effects
Anti-Bacterial Agents/pharmacology/therapeutic use
Fecal Microbiota Transplantation
Probiotics/therapeutic use
*Bacterial Infections/microbiology/therapy/prevention & control
*Drug Resistance, Bacterial
Phage Therapy
*Bacteria/drug effects
Antimicrobial Peptides/therapeutic use

@article {pmid41265661,
year = {2025},
author = {Cao, P and Li, Y and Zhang, S and Li, C and Sun, Y and An, B},
title = {Study on the efficacy and mechanism of fecal microbiota transplantation for depression based on circadian rhythm.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106186},
doi = {10.1016/j.bbi.2025.106186},
pmid = {41265661},
issn = {1090-2139},
abstract = {BACKGROUND: Depression is closely associated with disruptions in circadian rhythms, and emerging evidence highlights critical roles of gut dysbiosis in its pathogenesis. However, the mechanisms by which FMT chronotherapy influences circadian gene in depression-via gut microbiota-remain poorly understood.

METHODS: In this study, we established a chronic unpredictable mild stress (CUMS) mouse model and performed fecal microbiota transplantation (FMT) using donor microbiota from healthy mice at two distinct circadian time points-zeitgeber time (ZT) 4 or ZT16 to identify the optimal timing for FMT based on behavioral assessments. Integrating omics dependent mechanisms of antidepressant effects mediated by these key functional bacteria.

RESULTS: Health-FMT significantly alleviated depressive-like behaviors, with superior efficacy at ZT4. It restored circadian gene expressions and attenuated neuroinflammation expression in the hippocampus and prefrontal cortex. 16S rRNA sequencing revealed that Health-FMT reduced uncultured_bacterium_g_Alistipes abundance, a genus linked to tryptophan availability. Tryptophan supplementation regulated circadian gene expressions, inflammatory factors, brain-derived neurotrophic factors (BDNF), microglial and astrocytic activation, and exerted antidepressant effects via the ERK signaling pathway.

CONCLUSIONS: These findings suggest that Health-FMT exerts antidepressant effects by restoring gut homeostasis, particularly by reducing Alistipes, thereby rebalancing tryptophan metabolic and circadian gene expressions. These findings offer a new possible mechanism and novel insights into the microbiota-gut-brain axis in depression, and underscore the importance of chronotherapy in FMT-based therapeutic strategies.},
}

@article {pmid41265501,
year = {2025},
author = {Yan, S and Xie, Y and Xv, J and Wang, K and Wang, J and Cao, Y and Han, X and Chen, F and Zhou, L and Jiang, Y and Liu, Y},
title = {Shengjiang San attenuates sepsis-induced acute intestinal injury via Lactobacillus murinus derived IAAld-mediated macrophage polarization through NF-κB and TGF-β signaling.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120910},
doi = {10.1016/j.jep.2025.120910},
pmid = {41265501},
issn = {1872-7573},
abstract = {ETHNOPHARMACOLOGY ASSOCIATED: Sepsis is a life-threatening condition triggered by a dysregulated host response to infection, characterized by uncontrolled systemic inflammation and often culminating in multiple organ damage. Shengjiang San (SJS), a classic traditional Chinese medicinal (TCM) formula, has been historically utilized for its efficacy in removing heat, resolving toxicity, and reducing inflammation. Nevertheless, the precise role and mechanisms through which SJS modulates inflammatory responses and protects against sepsis-induced multi-organ injury are not yet fully understood.

OBJECTIVE: To investigate the protective mechanisms of SJS that improve sepsis-induced acute intestinal injury (SAII) by modulating the abundance and metabolism of the gut microbiota.

METHODS: A sepsis animal model was established using cecal ligation and puncture. The protective effects of SJS in SAII were evaluated through behavioral assessments, enzyme-linked immunosorbent assay, histological examination, and immunofluorescence analysis. Fecal samples were subjected to 16S rRNA sequencing and non-targeted metabolomics to identify probiotic taxa and metabolites associated with SJS administration. Proteomic analysis integrated with network pharmacology was performed to explore the underlying mechanisms. Fecal microbiota transplantation (FMT) and microbial metabolite analysis were utilized to elucidate the potential mechanism.

RESULTS: SJS was observed to significantly improve clinical scores, reduce pro-inflammatory cytokines, including IL-6, TNF-α and IL-1β. SJS also restored integrity of the intestinal barrier by upregulating the expression of ZO-1 and Claudin-1. 16S rRNA sequencing analysis demonstrated that SJS induced significant restructuring of the gut microbiota, including a marked increase in Lactobacillus murinus (L.M.) abundance. Proteomic and network pharmacological analyses revealed that SJS was protected against SAII by inhibiting NF-κB-mediated M1 polarisation while promoting TGF-β-mediated M2 polarisation. In particular, this protective effect was found to depend on the abundance of L.M., which regulated intestinal inflammation through its specific metabolites, indoleacetaldehyde (IAAld).

CONCLUSION: SJS improves SAII by orchestrating L.M. derived IAAld-mediated macrophage polarization through modulation of NF-κB and TGF-β signaling pathways.},
}

@article {pmid41263913,
year = {2025},
author = {Merrick, B and Prossomariti, D and Kertanegara, M and Wyatt, D and Goldenberg, S},
title = {Facilitators and barriers to recruitment and retention in a feasibility trial of encapsulated faecal microbiota transplant to eradicate carriage of antibiotic-resistant bacteria at an academic hospital in central London: a nested qualitative study.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e104783},
doi = {10.1136/bmjopen-2025-104783},
pmid = {41263913},
issn = {2044-6055},
mesh = {Humans ; London ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Feasibility Studies ; Middle Aged ; Qualitative Research ; Adult ; Focus Groups ; *Patient Selection ; COVID-19/epidemiology ; Aged ; *Carrier State/therapy ; },
abstract = {OBJECTIVES: This nested qualitative study (NQS) aimed to identify facilitators and barriers to the delivery of a substantive randomised controlled trial investigating the eradication of gastrointestinal tract carriage of antibiotic-resistant organisms using encapsulated faecal microbiota transplant (FMT).

DESIGN: NQS within a participant-blinded, randomised, placebo-controlled, single-centre, feasibility trial (RCT)-Feasibility of ERadicating gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO) (ISRCTN reg. no. 34 467 677)-with data collected via focus groups and analysed using thematic analysis.

SETTING: RCT participants were recruited from a large academic tertiary referral hospital in central London. Focus groups were held at the hospital or via videoconferencing for those unable to travel.

PARTICIPANTS: This study included 13 FERARO study participants across two focus groups. 11 participants were under RCT follow-up and unaware of their treatment allocation, two participants had completed 6-month follow-up and knew whether they had received FMT or matched placebo. Additional data were opportunistically collected on reasons for declining RCT participation.

RESULTS: Participants found FMT to be an acceptable and holistic management strategy and noted positive impacts from RCT participation including enhanced personal health awareness and valuable support from the research team. The time and travel commitment presented the most substantial barrier to RCT participation. Many participants were motivated by a desire to give something back to the UK National Health Service and/or research. Patients' current health status also influenced the decision-making process, and, while infrequently cited, the COVID-19 pandemic added extra complexity likely impacting individuals' willingness to participate.

CONCLUSIONS: While FMT is generally acceptable to participants, logistical barriers such as the time and travel commitment associated with RCT participation need consideration. Effective communication, personal connections and participant education on antimicrobial resistance are likely to be crucial for enhancing recruitment and retention in future trials.

TRIAL REGISTRATION NUMBER: ISRCTN registration number 34 467 677 and EudraCT number 2019-001618-41.},
}

Humans
London
*Fecal Microbiota Transplantation/methods
Male
Female
Feasibility Studies
Middle Aged
Qualitative Research
Adult
Focus Groups
*Patient Selection
COVID-19/epidemiology
Aged
*Carrier State/therapy

@article {pmid41263574,
year = {2025},
author = {Tang, L and Xie, P and Wang, H and Hong, X and Gong, Z and Zhao, G and Yue, M},
title = {The sex hormone-gut microbiome axis: mechanistic drivers of sex-disparate bacterial infection outcomes and precision clinical interventions.},
journal = {Clinical microbiology reviews},
volume = {},
number = {},
pages = {e0023625},
doi = {10.1128/cmr.00236-25},
pmid = {41263574},
issn = {1098-6618},
abstract = {SUMMARYSex disparities in bacterial infections pose significant challenges in clinical microbiology, influencing diagnostic approaches, antimicrobial stewardship, and patient outcomes. Males frequently exhibit heightened severity in conditions like Helicobacter pylori-associated gastritis and Vibrio cholerae outbreaks, whereas females face amplified risks during reproductive phases for pathogens, such as Listeria monocytogenes and Salmonella spp. Beyond genetic and behavioral factors, the bidirectional sex hormone-gut microbiome axis emerges as a key mechanistic driver: estrogens bolster innate immunity and microbial diversity (e.g., enriching short-chain fatty acid-producing taxa like Bifidobacterium), while androgens and progesterone impose immunosuppressive effects, altering colonization resistance and virulence modulation. Microbial contributions-via β-glucuronidase-mediated hormone deconjugation, bile acid biotransformations, and metabolite signaling-further calibrate host responses, as evidenced in Clostridioides difficile recurrence and enterohemorrhagic Escherichia coli virulence upregulation. This review synthesizes epidemiological, preclinical, and emerging clinical data, highlighting the axis's role in pathogen-specific immune evasion and dysbiosis-driven exacerbations. Clinically, these insights advocate for sex-stratified microbiome diagnostics (e.g., 16S rRNA sequencing for risk profiling) and targeted therapies, including hormone-modulated probiotics to restore barrier function, fecal microbiota transplantation to curb antibiotic-associated vulnerabilities, and selective estrogen receptor modulators to enhance clearance in high-risk cohorts. Despite advances, gaps in human longitudinal studies and pathogen-strain interactions limit translation. Future research integrating multi-omics with clinical trials could refine precision interventions, optimizing infection management in diverse populations and aligning with evolving demands for personalized microbiology.},
}

@article {pmid41263392,
year = {2025},
author = {Zhao, R and Lu, Y and Xu, Q and Ren, H and Li, H and Gao, J and Cui, H and Yuan, Z and Cao, B and Wei, B},
title = {Gut blautia coccoides-derived 5Z-dodecenoic acid attenuates chronic psychological stress-induced gastric cancer progression.},
journal = {International journal of surgery (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/JS9.0000000000004080},
pmid = {41263392},
issn = {1743-9159},
abstract = {BACKGROUND: Chronic psychological stress is a critical oncogenic factor of gastric cancer (GC). However, the mechanisms underlying stress-induced malignant progression remain largely unknown. Gut microbiota dysregulation is tightly associated with cancer development and metabolism.

MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS) modeling was used to prepare mice suffering from chronic psychological stress. 16s rRNA sequencing and Q300 targeted metabolite quantification were jointly conducted to depict landscapes of gut microbiome and metabolomics of CUMS mice. Fecal microbiota transplantation was employed to investigate the functions of gut microbial communities in regulating CUMS-mediated GC growth. Drug affinity responsive target stability, surface plasmon resonance and molecular docking assays were performed to screen direct target proteins of 5Z-dodecenoic acid. The interactions between RIOK2 and BYSL were verified with co-immunoprecipitation and GST pull-down and fluorescent co-localization analysis. A series of experiments for malignant behaviors and glycolysis and subcutaneous tumor transplantation were employed to detect alterations of GC cell phenotypes ex vivo and in vivo, respectively.

RESULTS: Microbiome and metabolomics collectively demonstrated disrupted gut microbial communities and metabolic patterns. Particularly, Blautia coccoides-derived 5Z-dodecenoic acid was predominately declined by CUMS. Supplementation with Blautia coccoides or 5Z-dodecenoic acid effectively mitigated the negative effects of CUMS on glycolysis and malignancy. Mechanistically, 5Z-dodecenoic acid directly inhibits the functions of RIOK2, which maintained ectopic glycolysis and malignant behaviors. RIOK2 further interacted with BYSL and maintained its properties of potentiation of GC progression and metabolism.

CONCLUSION: Our findings advance the insights of Blautia coccoides-derived 5Z-dodecenoic acid implicated in chronic psychological stress-induced GC progression and provide novel strategies for dampening GC progression.},
}

@article {pmid41263038,
year = {2025},
author = {Wang, M and Sun, H and Wang, X and Zhang, X and Huang, Y and Cui, R and Sun, Y and Yao, H and Wan, JY},
title = {Tangerine Peel-Based Herbal Formula Ameliorates Metabolic Syndrome via Gut Microbiota-Mediated Bile Acid Remodeling and TGR5 Activation.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-19},
doi = {10.1142/S0192415X25500946},
pmid = {41263038},
issn = {1793-6853},
abstract = {The growing global burden of metabolic syndrome (MetS), a key driver of multiple chronic diseases, highlights the limited treatment options for its multifactorial pathophysiology. Tanshi-Tiaoti Decoction (TTD), a Chinese herbal formula comprised of Citri Reticulatae Pericarpium (Tangerine peel), Coicis Semen (Raw coix seed/Job's tears), Raphani Semen (Radish seed), Nelumbinis Folium (Lotus leaf), Eckloniae/Laminariae thallus (Kelp), and Crataegi Fructus (Raw hawthorn fruit), demonstrates efficacy in the clinical management of MetS. However, its underlying molecular mechanisms remain incompletely elucidated. This study indicates that TTD restored gut microbiota homeostasis and bile acid (BA) profiles in high-fat diet (HFD)-induced MetS mice. TTD significantly attenuated body weight gain, fasting glucose levels, serum triglycerides, and hepatic steatosis. TTD corrected gut microbiota dysbiosis, most notably by reducing the Firmicutes/Bacteroidetes ratio. Fecal microbiota transplantation (FMT) validated the fact that the gut microbiome mediates TTD's therapeutic effects. TTD regulated BA biosynthesis through this microbial modulation, and thus specifically increased hyodeoxycholic acid (HDCA). HDCA, which has been identified as the signature BA during TTD treatment, phenocopied TTD's therapeutic effects against MetS by both activating the BA receptor TGR5 and subsequently promoting beige adipocyte browning. Collectively, TTD ameliorates MetS by reshaping microbial-mediated BA pools, and in particular elevates HDCA levels to thereby activate TGR5 and induce beige adipocyte browning. These findings support TTD as a promising herbal-based therapeutic strategy for the treatment of MetS.},
}

@article {pmid41260222,
year = {2025},
author = {Wang, Y and Wu, J and Yao, J and Chen, J and Cheng, KKY and Ho, MY and Lee, CH and Lam, KS and Tse, MA and Panagiotou, G and Xu, A},
title = {Gut microbiome-adipose crosstalk modulates soluble IL-6 receptor influencing exercise responsiveness in glycemic control and insulin sensitivity.},
journal = {Cell metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmet.2025.10.013},
pmid = {41260222},
issn = {1932-7420},
abstract = {Exercise is an effective intervention for the prevention and management of diabetes, but the high interpersonal variability in response to exercise impedes its widespread implementation. Herein, we identify adipocyte-derived soluble interleukin-6 receptor (sIL-6R) as a key exerkine determining exercise efficacy in improving metabolic health. In individuals with obesity who underwent a 12-week exercise intervention, circulating sIL-6R level exhibits dichotomous changes between exercise responders (Rs) and non-responders (NRs), in close association with exercise-mediated alterations in insulin sensitivity and glycemic control. Mechanistically, elevated gut microbiome-mediated leucine in NR acts on white adipocytes to promote disintegrin and metalloproteinase 17 (ADAM17)-mediated sIL-6R production via the mammalian target of rapamycin (mTOR)-hypoxia-inducible factor 1α (HIF1α) pathway, which in turn impairs the metabolic benefits of exercise through interleukin (IL)-6 trans-signaling-induced adipose inflammation. Adipocyte-selective ablation of ADAM17 prevents the effects of fecal microbiota transplantation from NR on elevation of sIL-6R, thereby restoring the efficacy of exercise-shaped gut microbiome in counteracting glucose intolerance and insulin resistance in obese mice. Thus, therapeutic interventions targeting adipocyte-derived sIL-6R represent a promising strategy for maximizing exercise efficacy in personalized diabetes prevention.},
}

@article {pmid41258493,
year = {2025},
author = {Xu, Q and Lin, A and Jiang, A and Chen, L and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Miao, K and Luo, P},
title = {Circadian rhythms as a modulator of gut microbiota-tumor microenvironment crosstalk.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {82},
number = {1},
pages = {409},
pmid = {41258493},
issn = {1420-9071},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Circadian Rhythm/physiology ; *Tumor Microenvironment ; Animals ; *Neoplasms/microbiology/pathology/therapy ; Dysbiosis/microbiology ; },
abstract = {Circadian rhythms play a pivotal role in regulating diverse physiological functions, notably the composition and activity of gut microbiota. Accumulating evidence indicates that circadian rhythm disruption can induce dysbiosis of the gut microbiome, which in turn is implicated in influencing the tumor microenvironment (TME) and facilitating cancer progression. This review integrates and analyzes recent advances elucidating the complex interplay where circadian rhythms modulate gut microbiota, and how these circadian-driven microbial changes affect the TME. This review analyzes recent advances in elucidating the complex interplay among circadian rhythms, gut microbiota, and the TME. We examine how circadian disruption modifies the diversity and metabolic functions of gut microbiota, resulting in alterations of microbial metabolites, including but not limited to short-chain fatty acids and secondary bile acids. These metabolic alterations have the potential to modulate immune cell function, vascular remodeling, and tumor cell metabolism within the TME. We investigate the potential mechanisms through which gut microbial dysbiosis induced by circadian misalignment could promote an immunosuppressive TME and accelerate tumor growth. Additionally, we evaluate emerging therapeutic strategies that leverage the circadian-microbiome axis, encompassing chronotherapy, probiotic supplementation, and fecal microbiota transplantation. The integration of circadian biology, microbiology, and cancer immunology presents promising avenues for the development of novel diagnostic and therapeutic approaches. However, significant challenges persist in translating these findings into viable clinical applications. Further research is imperative to elucidate the molecular pathways interconnecting circadian rhythms, gut microbiota, and the TME, and to develop personalized chronobiological interventions for cancer prevention and treatment.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Circadian Rhythm/physiology
*Tumor Microenvironment
Animals
*Neoplasms/microbiology/pathology/therapy
Dysbiosis/microbiology

@article {pmid41255657,
year = {2025},
author = {Vaou, N and Zavras, N and Fessatou, S and Voidarou, CC and Vrioni, G and Tsakris, A and Vaos, G},
title = {Microbiota decolonization of bacterial pathogens in pediatric surgery-related intestinal disorders: Insights on current strategies and future outlook.},
journal = {World journal of clinical pediatrics},
volume = {14},
number = {4},
pages = {107722},
pmid = {41255657},
issn = {2219-2808},
abstract = {The significance of gut microbiota (GM) in human health is being increasingly researched. An imbalance in GM composition, known as dysbiosis, is linked to various and other health issues. In addition, antibiotics are the primary and most significant factors leading to major changes in the composition and function of the GM, which may result in colonization by antimicrobial-resistant (AMR) pathogens. Therefore, alternative antibiotic strategies for combating AMR pathogens are urgently needed. This narrative review highlights current knowledge regarding various pertinent strategies for decolonizing bacterial pathogens from GM and emphasizes decolonization therapies' critical role in pediatric surgical disorders. Strategies such as decontamination of the digestive tract utilizing antibiotics, the use of probiotics, and particularly fecal microbiota transplantation have introduced new options for clinical treatment. These treatments show the potential to restore GM balance and have demonstrated advantages for intestinal disorders related to pediatric surgery, including inflammatory bowel disease, neonatal necrotizing enterocolitis, Hirschsprung-associated enterocolitis, and short bowel syndrome. Despite GM therapeutics, recent strategies are still in their developmental phase and exhibit challenges that need further research. Thus, potential future directions for GM-targeted decolonization therapies are under consideration. Innovative alternative strategies to combat AMR though GM modulation in disorders related to pediatric surgery appear to be promising and should continue to be prioritized for further research and development.},
}

@article {pmid41255529,
year = {2025},
author = {Horiachok, M and Potapova, K and Ivanykovych, T and Yerokhovych, V and Ilkiv, Y and Sokolova, L},
title = {Integrating gut microbiota into multidisciplinary perspectives on diabetic neuropathy.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1710868},
pmid = {41255529},
issn = {1664-2392},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetic Neuropathies/microbiology/therapy/metabolism ; *Dysbiosis/microbiology ; Animals ; Probiotics/therapeutic use ; },
abstract = {Diabetic neuropathy (DN) is one of the most common and debilitating complications of diabetes mellitus, yet its precise pathogenesis remains incomplete. Emerging evidence highlights the gut microbiome as a key factor linking metabolic dysfunction, immune activation, and neuronal damage. Even minor dysbiosis may interfere with microbial metabolite balance and disrupt intestinal integrity, leading to local and, consequently, systemic inflammation, which in turn drives altered pain response via the gut-brain-immune axis. Recent clinical and preclinical data show that reduced short-chain fatty acid availability, altered bile acid and tryptophan metabolism, let alone expansion of pro-inflammatory species collaboratively contribute to DN onset and progression. Moreover, advances in metagenomics and metabolomics reveal reproducible microbiome-derived biomarkers that could predict neuropathy risk and pain phenotypes independent of glycemic control, supporting the microbiome as both a mechanistic driver and a measurable potential diagnostic tool. In the context of management, microbiota-affected interventions, such as probiotics, synbiotics, omega-3 supplementation, and fecal microbiota transplantation, show early promise in alleviating symptoms and improving nerve function. This mini-review synthesizes current evidence on the microbiome's role in DN, emphasizing its dual potential as a biomarker for early diagnosis and a therapeutic target for precision microbiome-based interventions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Diabetic Neuropathies/microbiology/therapy/metabolism
*Dysbiosis/microbiology
Animals
Probiotics/therapeutic use

@article {pmid41255078,
year = {2025},
author = {Ghoshal, UC and Ramakrishna, BS and Rathi, PM and Shukla, A and Panigrahi, MK and Jain, S and Saha, I and Chakravartty, K and Singh, M and Mustafa, U and Sahu, S and Ghoshal, U and Chandnani, S and Goenka, MK and Mitra, M},
title = {Probiotic Blend of Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. Lactis BB-12 in Non-constipated Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.},
journal = {Journal of gastroenterology and hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgh.70137},
pmid = {41255078},
issn = {1440-1746},
support = {//Zydus Healthcare Limited and Shanti Public Educational and Development Society/ ; },
abstract = {BACKGROUND: As dysregulated gut microbiota is known in irritable bowel syndrome (IBS) and probiotics may improve it, we investigated the efficacy and safety of a combination probiotic, Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. lactis BB-12 in non-constipated IBS.

METHODS: Two hundred non-constipated IBS patients were randomized to the above-mentioned probiotic and placebo for 84 days. The outcome measures included IBS-Global Improvement Scale (IBS-GIS), IBS-Quality of Life (IBS-QoL), EAR3Q, IBS-Severity Scoring System (IBS-SSS), and patient-reported improvement. Fecal microbiota was evaluated in a subset.

RESULTS: Response in IBS-GIS was higher with probiotics than with placebo at days 28 (19.3% vs. 8.9%; p = 0.048), 56, and 84. Total and abdominal pain, distension, and QoL scores of IBS-SSS decreased at day 28 with probiotics that persisted till days 56 and 84. The percentage of patients with "severe" symptoms reduced from 20.8% at baseline to 3.9% at day 84, and the median IBS-QoL score decreased significantly at day 28; the beneficial effect on QoL was sustained till days 56 and 84 (p < 0.001). Improvement in abdominal pain, distension, urgency of defecation, bowel habit satisfaction, and stool frequency was noted earlier with probiotics than with placebo; 4.0% in the probiotic group and 0.9% in the placebo group had mild/moderate adverse events (p = 0.167). Symptom recurrence occurred in 3.0% in the probiotic group and 3.9% in the placebo group during follow-up of 180 days (p = 0.718). No difference was observed in the fecal microbiota between the two groups, but healthy genera were enriched with probiotics.

CONCLUSIONS: The probiotic blend studied was more effective than placebo in non-constipated IBS in adults.},
}

@article {pmid41254951,
year = {2025},
author = {González-Correa, C and Miñano, S and Moleón, J and Toral, M and Robles-Vera, I and Sánchez, M and Jiménez, R and Olivares, M and Martín-Morales, N and O'Valle, F and Guerra-Hernández, E and Romero, M and Gómez-Guzmán, M and Duarte, J},
title = {The probiotic Limosilactobacillus fermentum CECT5716 enhances the antihypertensive response to hydrochlorothiazide in spontaneously hypertensive rats.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2586324},
doi = {10.1080/19490976.2025.2586324},
pmid = {41254951},
issn = {1949-0984},
mesh = {Animals ; Rats, Inbred SHR ; *Hydrochlorothiazide/pharmacology/administration & dosage/therapeutic use ; *Probiotics/administration & dosage/pharmacology ; *Hypertension/drug therapy/microbiology/physiopathology ; Gastrointestinal Microbiome/drug effects ; Rats ; *Antihypertensive Agents/pharmacology/administration & dosage/therapeutic use ; Male ; *Limosilactobacillus fermentum/physiology ; Blood Pressure/drug effects ; Fecal Microbiota Transplantation ; },
abstract = {Limosilactobacillus fermentum CECT5716 (LC40) consumption reduces hypertension and improves endothelial dysfunction in spontaneously hypertensive rats (SHRs). The diuretic hydrochlorothiazide (HCTZ) lowers blood pressure in SHR but disrupts the gut microbiota balance. In this study, we investigated whether the LC40 could enhance the antihypertensive effects of HCTZ. Interestingly, we found that coadministration of LC40 with HCTZ potentiated the beneficial effects of HCTZ on endothelial dysfunction and blood pressure without altering plasma HCTZ concentrations or exacerbating electrolyte imbalances. These protective effects were associated with normalization of microbiota alterations, including a reduction in the Firmicutes/Bacteroidota ratio, suppression of lipopolysaccharide biosynthesis, and an increase in acetate-producing bacteria. Additionally, LC40 reduced intestinal pathology and endotoxemia. Furthermore, the HCTZ + LC40-treated rats exhibited reduced neuroinflammation and sympathetic activity, along with an immunoregulatory effect characterized by increased regulatory T cell infiltration and a reduction of vascular oxidative stress in the aorta. The beneficial effects of LC40 in HCTZ-treated rats appeared to be microbiota dependent, as they were replicated through fecal microbiota transplantation in germ-depleted normotensive rats. Our findings identify the gut microbiota as a novel therapeutic target to enhance the antihypertensive effects of diuretics. The coadministration of LC40 with HCTZ modulates immune responses, providing a promising strategy to improve hypertension management.},
}

Animals
Rats, Inbred SHR
*Hydrochlorothiazide/pharmacology/administration & dosage/therapeutic use
*Probiotics/administration & dosage/pharmacology
*Hypertension/drug therapy/microbiology/physiopathology
Gastrointestinal Microbiome/drug effects
Rats
*Antihypertensive Agents/pharmacology/administration & dosage/therapeutic use
Male
*Limosilactobacillus fermentum/physiology
Blood Pressure/drug effects
Fecal Microbiota Transplantation

@article {pmid41253445,
year = {2025},
author = {Chen, YL and Meng, LL and Wu, JY and Yang, XY and Ouyang, L and Wu, BF and Xu, HX and Gu, JL and Wang, YL and Jing, XY and Lu, SF and Fu, SP},
title = {Electroacupuncture Reprograms Gut Microbiota and Confers Cerebral Protection After Stroke through Enhanced Regulatory T Cell Response.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-24},
doi = {10.1142/S0192415X25500855},
pmid = {41253445},
issn = {1793-6853},
abstract = {Ischemic stroke seriously endangers both the health and quality of life of patients. The gut microbiota, which plays a crucial role in modulating communication between the gut and the nervous system, has emerged as a promising target for therapeutic interventions in stroke. Electroacupuncture (EA), which is associated with intestinal immunity, has been proven to exert significant beneficial effects in ischemic stroke, but its exact mechanism remains unclear. In this study, we investigated the regulatory mechanism of EA on the microbiome-gut-brain axis following ischemic stroke. In rat models of ischemic stroke, EA treatment significantly reduced cerebral infarct volume and neuronal damage following cerebral ischemia-reperfusion injury, and also modulated the composition, diversity, and taxonomic distribution of the gut microbiota. Fecal microbiota transplantation from EA-treated donors significantly reduced cerebral infarct volume and neuronal damage in the ischemic hemisphere of recipient mice, and likewise upregulated Treg cell expression to suppress immune-inflammatory responses in the brain. These results indicate that, through modulation of the gut microbiota, which in turn regulates Treg-mediated immune-inflammatory responses, EA ameliorates cerebral ischemic injury to thereby improve the prognosis of ischemic stroke patients. This study provides new perspectives on the efficacy of EA in the treatment of ischemic stroke.},
}

@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.},
}