@article {pmid41390118,
year = {2025},
author = {Dai, Z and Bao, X and Jiang, H and Zhang, Y and Shen, Q and Xue, Y},
title = {Grain proteins ameliorate glucose metabolism disorders by activating intestinal AhR and the hepatic NLK/FOXO1 pathway via gut microbiota-derived indole metabolites.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.12.010},
pmid = {41390118},
issn = {2090-1224},
abstract = {INTRODUCTION: Consumption of gran proteins has been associated with lower risk of type 2 diabetes (T2D), but the underlying mechanisms remain unclear. Gut microbiota plays a key role in glucose metabolism, and dietary proteins can modulate microbial composition and function.

OBJECTIVE: This study aims to evaluate the effects of grain proteins on glucose metabolism, identify key gut microbiota-derived metabolites, and elucidate the molecular mechanisms underlying grain protein-mediated glucose metabolism regulation.

METHODS: Glucose homeostasis and gut microbiota composition were assessed in mice fed a high-fat diet (HFD) supplemented with proteins isolated from rice, soybean, highland barley (HB), oats, and quinoa. The alterations in gut microbiota and their causal roles in glucose regulation were determined by in vitro fermentation and fecal microbiota transplantation (FMT). Key tryptophan (Trp) metabolites in fecal and serum samples were identified, and their glucose-regulating effects were validated in mice and HepG2 cells. Liver transcriptomics and molecular analyses were subsequently performed to elucidate the underlying regulatory pathways.

RESULTS: HB, oat, and quinoa proteins significantly improved glucose metabolism, increased Lactobacillus and Bifidobacterium abundance, and enriched Trp-derived metabolites. FMT reproduced the metabolic improvements in recipient mice, supporting a microbiota-mediated mechanism. Among Trp metabolites, indole-3-ethanol (IEt), indole-3-acrylic acid (IArA), and indole-3-aldehyde (IAld) promoted glucose homeostasis via aryl hydrocarbon receptor (AhR) activation and intestinal homeostasis maintenance. Cell-based and liver transcriptomic analyses demonstrated that these metabolites suppressed hepatic gluconeogenesis by modulating the Nemo-like kinase (NLK)/forkhead box protein O1 (FOXO1)/phosphoenolpyruvate carboxykinase 1 (PCK1)/glucose-6-phosphatase (G6PC) pathway.

CONCLUSIONS: Grain proteins diet-induced alleviate glucose metabolic disorders by enriching gut microbiota-derived indole metabolites, which improve intestinal homeostasis and inhibit hepatic gluconeogenesis through AhR and NLK/FOXO1 signaling. These findings highlight the therapeutic potential of grain proteins for T2D prevention and management.},
}

@article {pmid41389504,
year = {2025},
author = {Meenakshi, S and Amrutha, TV and Abubakar, M and Prakash, V and Kumar, N and Murti, K},
title = {Fluoride-induced gut dysbiosis in metabolic disorders: Mechanisms and public health implications.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {93},
number = {},
pages = {127806},
doi = {10.1016/j.jtemb.2025.127806},
pmid = {41389504},
issn = {1878-3252},
abstract = {AIM: This review explores the effects of fluoride exposure and metabolic alterations linked to obesity and diabetes, and highlights preventive and therapeutic approaches to mitigate fluoride-driven metabolic risks.

SUMMARY: While fluoride is beneficial to dental health, but excessive exposure disrupts gut microbiota composition, reducing short-chain fatty acids (SCFA) production and impairing intestinal barrier integrity. These disruptions alter the oxidative stress, inflammation and insulin resistance. Evidence from animal and human studies suggest a dose-dependent pattern, with depletion of beneficial bacteria such as Lactobacillus and Faecalibacterium and enrichment of pro-inflammatory microbes. Such microbial imbalances influence bile acid metabolism. lipopolysaccharide (LPS) translocation and glucose regulation. This review discusses potential microbiome modulating strategies include probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT) and glucose lowering agents such as metformin and GLP-1 receptor agonists as possible therapeutic interventions to restore microbial balance and improve metabolic outcome However, the long-term and epigenetic effects of fluoride on intestinal and metabolic health remain unclear.

CONCLUSION: Since fluoride contaminates drinking water in areas with an endemic tendency, defluoridation, exposure monitoring, and public awareness are essential preventive strategies. Future mechanistic and clinical studies are necessary to elucidate the pathways linking fluoride metabolic disease progression.},
}

@article {pmid41389450,
year = {2025},
author = {Mittal, A and Sharma, S},
title = {Gut microbiota and nutritional interventions in alcohol-associated liver disease: Mechanisms and therapeutic advances.},
journal = {Nutrition research (New York, N.Y.)},
volume = {145},
number = {},
pages = {8-24},
doi = {10.1016/j.nutres.2025.11.004},
pmid = {41389450},
issn = {1879-0739},
abstract = {Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. Despite growing awareness of its burden, treatment options remain limited, with abstinence as the only widely accepted intervention. Recent research underscores the critical role of the gut-liver axis and nutritional status, particularly dietary protein, in modulating ALD pathogenesis and progression. This review aims to integrate current knowledge on the interplay between gut microbiota, dietary protein, and alcohol-induced liver injury, and to evaluate microbiota-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), within this context. We examine how chronic alcohol intake reshapes the gut microbiome, impairs barrier function, and alters microbial metabolism. We discuss how dietary protein, based on source, quantity, and amino acid composition, influences microbial ecology and metabolite profiles, with plant and dairy proteins emerging as beneficial. The review also highlights advances in FMT, which shows promise in improving outcomes in severe alcoholic hepatitis. However, its efficacy is modulated by donor microbial composition and recipient compatibility, both of which may be influenced by diet. Furthermore, we address emerging evidence on the role of fungal and viral communities, which remain understudied contributors to ALD. Despite substantial progress, significant knowledge gaps persist. These include the need for clinical validation of preclinical findings, deeper exploration of nonbacterial microbiota, and a lack of personalized, nutrition-based interventions. Addressing these gaps through integrative, multiomic approaches will be essential to advancing precision therapeutics in ALD.},
}

@article {pmid41388767,
year = {2025},
author = {Hou, B and Shao, H and Yuan, D and Tham, EH},
title = {Skin and gut microbiome in atopic dermatitis: Mechanisms and therapeutic opportunities.},
journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology},
volume = {36},
number = {12},
pages = {e70265},
doi = {10.1111/pai.70265},
pmid = {41388767},
issn = {1399-3038},
support = {//National Medical Research Council/ ; },
mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; *Skin/microbiology/immunology ; *Dysbiosis/immunology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; },
abstract = {The pathogenesis of atopic dermatitis (AD) comprises a combination of genetic, immune, and microbial factors. An imbalance in skin and gut microbiota composition, termed dysbiosis, may contribute to AD pathogenesis and severity through overgrowth of pathogenic microbes and suppression of healthy commensal colonization. These, in turn, promote barrier disruption and pro-inflammatory responses. The skin and gut microbiota composition plays crucial roles in AD, namely as early predictive biomarkers of AD onset; indicators of treatment response; and as future novel therapeutics such as probiotics, fecal, and skin microbiota transplantation. Such interventions aim to directly "reset" and restore a healthy microbial equilibrium, thereby fundamentally repairing barrier function, regulating immune homeostasis, and establishing new adjunctive pathways for the long-term management of AD.},
}

Humans
*Dermatitis, Atopic/therapy/microbiology/immunology
*Gastrointestinal Microbiome/immunology
*Skin/microbiology/immunology
*Dysbiosis/immunology/therapy
Probiotics/therapeutic use
Animals
Fecal Microbiota Transplantation

@article {pmid41387927,
year = {2025},
author = {Shi, F and Yang, Z and Zhang, L and Zou, D and Yu, J and Guo, N and Ren, S and Tang, X and Gu, C and Xu, R and Ru, Y and Zhang, Y and Wang, D},
title = {Deoxycholic acid derived from the gut microbiota involved in the regulation of adaptive thermogenesis in response to dietary protein restriction in plateau pika.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02233-4},
pmid = {41387927},
issn = {2049-2618},
support = {32301301//National Natural Science Foundation of China/ ; 32330012//National Natural Science Foundation of China/ ; 23-2-1-26-zyyd-jch//Natural Science Foundation of Qingdao/ ; ZR2024QC355//Natural Science Foundation of Shandong/ ; },
abstract = {BACKGROUND: Most winter-active mammals experience protein restriction. Gut microbiota is a key regulator of host energy homeostasis during nutrient deficiency, yet cross talk between microbiota and factors (e.g., hormones, signaling molecules) that regulate host energy metabolism in a low-protein (LP) context has not been studied sufficiently.

RESULT: The LP diet triggered the hepatic FGF21 adaptive metabolic pathway, which increased thermogenesis and reduced body weight, and this adaptive response was dependent on the composition and function of gut microbiota. Specifically, the LP diet induced a reshaping of the gut microbiota, altering its metabolic profile to increase deoxycholic acid levels and thereby increasing UCP1-induced thermogenesis of brown adipose tissue in an FGF21-dependent manner. Fecal transplantation with LP-associated microbiota increased thermogenesis through activation of GCN2-eIF2α-FGF21 signaling. Supplementation of the LP diet with yak fecal bacteria in plateau pika reduced UCP1-associated thermogenesis by altering the gut microbiome, decreasing deoxycholic acid production, suppressing activation of GCN2-eIF2α-FGF21 signaling, and alleviating LP-induced weight loss.

CONCLUSIONS: Our study reveals an association between the gut microbiota and LP diet-associated regulation of FGF21 signaling and thermogenesis and further demonstrates that this relationship is influenced by interspecies microbial transfer, indicating a critical mechanism whereby horizontal microbial exchange between sympatric species enhances host energy homeostasis. These findings provide novel insights into our understanding of the adaptations of mammals to high-elevation environments. Video Abstract.},
}

@article {pmid41115624,
year = {2025},
author = {Mishra, R and Harvey, A and Guo, A and Tillotson, G and Feuerstadt, P and Khanna, S and Shannon, WD and Blount, KF},
title = {Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements.},
journal = {Anaerobe},
volume = {96},
number = {},
pages = {103006},
doi = {10.1016/j.anaerobe.2025.103006},
pmid = {41115624},
issn = {1095-8274},
mesh = {Humans ; *Quality of Life ; *Metabolome ; *Gastrointestinal Microbiome ; Male ; Female ; *Feces/microbiology ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/prevention & control/therapy/microbiology ; Adult ; Aged ; Clostridioides difficile ; },
abstract = {OBJECTIVES: Increasing evidence indicates a gut microbiome-brain axis, but more robust statistical methods are needed to solidify this connection. In a large phase 3, randomized, placebo-controlled clinical trial (PUNCH CD3; NCT03244644), fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660), was effective in preventing recurrent Clostridium difficile infections, and trial participants had significant gut microbiome and metabolome shifts concurrent with significant changes in health-related quality of life (HRQOL). Advanced statistical methods were applied to data from this trial to further explore and demonstrate associations between changing HRQOL and microbiome or metabolome changes.

METHODS: A categorical statistical analysis queried whether patient-reported Cdiff32 HRQOL scores were more likely to improve after RBL than after placebo among PUNCH CD3 participants, and a Dirichlet-multinominal recursive partitioning model assessed whether mental domain Cdiff32 HRQOL scores were linked to participants' fecal microbiome or bile acid compositions.

RESULTS: Cdiff32 mental domain HRQOL scores were more likely to be improved after RBL administration compared with placebo among treatment responders. Cdiff32 mental domain scores were associated with changing gut microbiome and metabolome compositions, with a gradient of increased Clostridia and Bacteroidia and increased secondary bile acid predominance associated with better Cdiff32 scores.

CONCLUSIONS: The microbiota-gut-brain axis is posited to modulate health-related quality of life, microbiome, and metabolome changes through immune, gastrointestinal, and central nervous system functions in patients with recurrent C. difficile infection following RBL administration. These analyses provide a novel approach for investigating multi-omics data and categorical health-related quality of life questionnaires and generate new insights for further clinical studies.

CLINICAL TRIAL REGISTRATION: NCT03244644.},
}

Humans
*Quality of Life
*Metabolome
*Gastrointestinal Microbiome
Male
Female
*Feces/microbiology
Middle Aged
*Fecal Microbiota Transplantation/methods
*Clostridium Infections/prevention & control/therapy/microbiology
Adult
Aged
Clostridioides difficile

@article {pmid41385953,
year = {2025},
author = {Pan, Z and Guo, J and Wang, H and Cai, Y and Wu, L and Zhang, J and Wu, L and Jia, X and Wang, Q and Yu, K and Shen, C and Zhao, L},
title = {Shenling Baizhu Powder attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157654},
doi = {10.1016/j.phymed.2025.157654},
pmid = {41385953},
issn = {1618-095X},
abstract = {BACKGROUND: Obesity is closely associated with cognitive dysfunction, and markedly increases the risk of developing neurodegenerative diseases. Currently, obesity-related cognitive impairment lacks effective therapeutic interventions. Shenling Baizhu Powder (SLBZ) is a classical formula used to strengthen the spleen and promote the ascent of clear qi in traditional Chinese medicine (TCM). According to the TCM, this formula has great potential for the treatment of obesity-related cognitive impairment. However, research on SLBZ has focused primarily on its gastrointestinal effects, leaving its neurocognitive mechanisms largely unexplored.

PURPOSE: This study aimed to elucidate the therapeutic mechanisms of SLBZ in obesity-related cognitive impairment.

MATERIALS AND METHODS: Obese mice were obtained by subjecting male mice to a 16-week high-fat diet (HFD, 60 kcal % fat). During the final four weeks of the study, a SLBZ decoction (10 and 20 g/kg/day) was administered orally. The mice were then subjected to two behavioral tests and a glucose tolerance test. To evaluate the therapeutic effects of HFD on metabolic dysregulation, neuroinflammation, and intestinal barrier impairment, a range of analytical techniques, including biochemical analysis, immunofluorescence, RT-qPCR, and Western blotting, were used. Subsequently, 16S rRNA gene sequencing and metabolomic profiling were used to detect changes in the gut microbes and metabolite levels. Finally, fecal microbiota transplantation was performed to assess the functional link between SLBZ remodeling of the gut microbiota, metabolic alterations, and hippocampal cognitive function.

RESULTS: Our study demonstrated that HFD-fed mice developed significant cognitive impairment, supporting the notion that obesity adversely affects cognitive function. In the Morris water maze and open-field tests, SLBZ administration effectively ameliorated HFD-induced cognitive dysfunction. This improvement was accompanied by the restoration of the hippocampal synaptic ultrastructure and the recovery of the key synaptic proteins BDNF and PSD95. In agreement with this, SLBZ suppressed microglial activation and associated neuroinflammatory responses in HFD-fed mice. In the colon, SLBZ administration markedly alleviated HFD-induced gut barrier impairment, as evidenced by increased colonic mucus thickness and elevated expression of tight junction proteins, ZO-1, Occludin, and Claudin-1. Furthermore, SLBZ reduced endotoxin translocation and downregulated the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Notably, HFD-induced gut microbiota dysbiosis was remodeled by the SLBZ treatment, which was characterized by an increased capacity for microbial vitamin B6 synthesis. SLBZ increased the serum levels of vitamin B6 in HFD-fed mice. Intriguingly, fecal microbiota transplantation from SLBZ-treated HFD-fed mice facilitated the amelioration of cognitive deficits, including superior performance in behavioral tests and synaptic repair in the hippocampus compared to recipients of HFD-microbiota.

CONCLUSION: Our findings highlight that SLBZ is a promising therapeutic agent mitigating obesity-related cognitive impairment via the "gut microbiota-vitamin B6-neuroprotection" axis.},
}

@article {pmid41385961,
year = {2025},
author = {Zhao, H and Akram, MZ and Comer, L and Corion, M and Fako, E and Everaert, N},
title = {Early life fecal microbiota transplantation enhances fermentation potential by changing the microbial profiles in broiler chickens.},
journal = {Poultry science},
volume = {105},
number = {1},
pages = {106189},
doi = {10.1016/j.psj.2025.106189},
pmid = {41385961},
issn = {1525-3171},
abstract = {The early gut microbiota of broiler chickens plays a critical role in shaping physiological functions later in life. Broilers have a limited capacity to utilize dietary fiber at an early stage of life. Fecal microbiota transplantation (FMT) can modify the gut microbial composition of broilers, potentially enhancing their fiber utilization capability. In this study, fecal samples from different chicken donors (broilers, laying hens, and broiler breeders) were collected and used for in vitro fermentation with two structurally distinct fibers, inulin and citrus pectin. FMT was then performed on newly hatched broilers, followed by additional in vitro fermentation to evaluate changes in the recipients' fiber fermentation capacity. Laying hen fecal microbiota exhibited the fastest fermentation rates for both fibers, while broilers showed the slowest. Notably, laying hens produced the highest levels of propionic acid during fermentation. These donor-specific fermentation differences were likely driven by Bacteroides, Subdoligranulum, Collinsella, Clostridium, and Bifidobacterium. The in vivo experiment demonstrated that FMT significantly altered the microbial composition and volatile fatty acid production in recipient broilers up to 14 days of age. Subsequent in vitro fermentation of the recipients' cecal content revealed that fermentation capacity was influenced by both the donor microbiota and the fiber substrate, with recipients of laying hen microbiota showing significantly enhanced propionic acid production, mirroring donor patterns. In conclusion, differences in donor fecal microbiota composition reflect their distinct capacities to utilize different fibers. Through FMT, recipient's cecal microbiota composition can be changed, and the donor's fermentative capacity is reflected in the recipients. These findings highlight the potential of early microbial interventions to improve fiber utilization in broilers, offering a promising strategy to optimize gut health.},
}

@article {pmid41384118,
year = {2025},
author = {Bautista, J and Cardona-Maya, WD and Gancino-Guevara, K and López-Cortés, A},
title = {Reprogramming prostate cancer through the microbiome.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1690498},
pmid = {41384118},
issn = {2296-858X},
abstract = {Prostate cancer (PCa) is a major global public health challenge, driven by a multifactorial interplay of genetic, epigenetic, hormonal and environmental determinants. In recent years, the human microbiome has emerged as a critical and previously underappreciated contributor to PCa initiation, progression, and therapeutic response. Emerging high-resolution multi-omics studies have demonstrated that microbial communities across the gut, urinary tract and prostate form a functional axis that shapes immune surveillance, hormonal metabolism, inflammatory tone and epigenetic regulation. Dysbiosis in these compartments promotes chronic inflammation, modulates androgen receptor signaling, and produces bioactive metabolites, including short-chain fatty acids, that activate oncogenic IGF-1/MAPK/PI3K and NF-κB/JAK/STAT pathways. Cross-compartmental trafficking of bacterial taxa and metabolites reinforces tumor-promoting circuits, while specific commensals such as Akkermansia muciniphila enhance antitumor immunity and improve responses to androgen deprivation therapy. Importantly, microbiota-derived factors also modulate microRNA (miRNAs) expression and epigenetic signatures, thereby affecting tumor plasticity and resistance to therapy. These mechanistic insights have catalyzed interest in microbiome-based therapeutic approaches, including probiotics, prebiotics, fecal microbiota transplantation, dietary modulation and bacteriophage therapy, which hold promise for restoring eubiosis and enhancing treatment efficacy. Nevertheless, clinical translation remains limited by inter-individual variability and the need for well-designed, longitudinal studies integrating shotgun metagenomics, metabolomics and host-microbe interactomics. Overall, the prostate, urinary and gut microbiomes represent interconnected targets that may inform precision diagnostics and novel therapeutic strategies in PCa.},
}

@article {pmid41383731,
year = {2025},
author = {Zhang, M and Liu, L and Lian, J and Zhang, M and Yang, X and Wang, H},
title = {Changes in gut microbiota in Gynura segetum-induced liver injury.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1684570},
pmid = {41383731},
issn = {1664-302X},
abstract = {INTRODUCTION: Gynura segetum (GS) has been shown to induce hepatotoxicity. Growing evidence suggests that the response to herbal medicines may be linked to shifts in the gut microbiota. This study aims to investigate the association between gut microbiota and liver injury induced by GS.

METHODS: The mice model of liver injury was established by oral gavage of GS decoction for 4 weeks, with or without the broad-spectrum antibiotics (Abx) or fecal microbiota transplantation (FMT). Liver function was assessed through the hematoxylin and eosin (H&E) staining and biochemical indices. The microbiota in the intestinal tract and peritoneal cavity were determined by 16S rRNA gene sequencing. Senecionine, seneciphylline, ferulic acid, beta-sitosterol, vanillic acid, vanillin, isorhamnetin, quercetin, kaempferol, and luteolin were isolated from GS plants, and the effects of these chemical compounds on the intestinal flora were analyzed.

RESULTS AND DISCUSSION: Compared to controls, mice treated with the GS decoction exhibited decreased body weight and increased serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, and aspartate aminotransferase, regardless of whether they were given Abx or FMT. The abundance of Akkermansia (phylum Verrucomicrobia) persistently increased in the GS group. In contrast, other bacterial groups showed different trends under Abx or FMT conditions. Additionally, compared with the GS group, the linear discriminant analysis (LDA) score revealed the increase in abundance of Bifidobacterium, Bacteroides, Ruminococcaceae_UCG-007, and Coriobacteriaceae_UCG-002 in the Abx group, and Blautia and Bifidobacterium in the FMT group. 16S sequencing of ascitic fluid detected multiple bacterial phyla. Moreover, the administration of chemical compounds isolated from the GS plant by gavage did not increase the abundance of Akkermansia in the intestine.

CONCLUSION: GS increased the relative abundance of the Akkermansia genus in the intestinal tract. None of the above chemical compounds had this effect. This suggests that some components of GS may promote the growth of beneficial bacteria such as Akkermansia, offering new perspectives for drug development.},
}

@article {pmid41383587,
year = {2025},
author = {Bibbò, S and De Maio, F and Capone, F and Quaranta, G and Rondinella, D and Rosato, R and Minelli, M and De Lorenzis, D and Sanguinetti, M and Cammarota, G and Di Lazzaro, V and Masucci, L},
title = {Case Report: Fecal microbiota transplantation via capsules ameliorated clinical outcomes in a patient with multiple sclerosis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1678759},
pmid = {41383587},
issn = {1664-3224},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Female ; Adult ; *Gastrointestinal Microbiome ; *Multiple Sclerosis/therapy/microbiology ; Treatment Outcome ; Capsules ; Dysbiosis/therapy ; },
abstract = {Multiple Sclerosis (MS) has long been recognized as a multifactorial disease, associated with both genetic and enviromental factors. Its link to inflammatory processes has led to significant advances in understanding the immunological and neurobiological mechanisms underlying the disease. The presumed autoimmune etiology is currently guiding the development of therapeutic protocols in this direction. The intestinal bacteria population, known as Gut Microbiota (GM), plays a well-documented role in autoimmune and inflammatory diseases. Gut microbiota dysbiosis is associated in patients affected by MS. Fecal Microbiota Transplantation (FMT) is emerging as a potential strategy to restore eubiosis and modulate systemic inflammation. We treated a 42-year-old woman with severe MS disability by FMT via colonoscopic infusion followed by a 3-month treatment of daily oral capsules, containing frozen microbiota, in order to resolve gastrointestinal symptoms. Clinical follow-up was conducted at 30, 60, and 90 days. Microbiota profiling (16S rRNA sequencing) and intestinal permeability testing were performed at several time points before and post infusion. Post-FMT, gastrointestinal symptoms improved significantly, as well as in limb spasticity, trunk stability, and fine motor skills. Microbiota analysis revealed a marked reduction in the abundance of Akkermansia muciniphila (22.5% vs 6.6%). At phylum level, Actinomycetota remained elevated (22%), while Bacteroidota consistently showed low abundance (14%). The most favorable microbiota profile was observed at 90 days, which coincided with the peak of clinical improvement. Intestinal permeability also improved over time, despite the patient's microbiota profile remaining distinct from the donor. This is the first report about combined FMT in MS. The procedure was safe, well tolerated, and associated with both gastrointestinal and neurological improvements. These findings support further exploration of FMT as a therapeutic adjunct in MS through controlled clinical trials.},
}

Humans
*Fecal Microbiota Transplantation/methods
Female
Adult
*Gastrointestinal Microbiome
*Multiple Sclerosis/therapy/microbiology
Treatment Outcome
Capsules
Dysbiosis/therapy

@article {pmid41381864,
year = {2025},
author = {Tang, A and Chen, Y and Si, K and Lai, J and Gong, W and Hu, S},
title = {Gut microbiota modulates synaptic plasticity, connectivity, and dopamine transmission in the VTA-mPFC pathway in bipolar depression.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41381864},
issn = {1476-5578},
support = {LR20F050002//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LR22F050007//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; 82201676//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82471542//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Adequate evidence has shown that gut microbial dysbiosis is an emerging disease phenotype of bipolar disorder (BD), and is closely related to clinical symptoms of this intractable disease. However, how gut microbiota affects the nervous system in BD remains largely unclear. In this study, we constructed a BD depression-like mouse model via fecal microbiota transplantation, and explored the changes of synaptic plasticity and connectivity in the medial prefrontal cortex (mPFC) of BD mice. We found that bipolar depression-like mice presented with a decrease in the density of dendritic spines in medial prefrontal neurons, and "Translation at postsynapse" as a key contributor to the changes in synaptic plasticity. In addition, analysis of synaptic connectivity in the mPFC revealed that compared to control mice, less connections were observed between ventral tegmental area and mPFC glutamate neurons and dopamine response was decreased in BD mice. These findings suggest that gut microbiota from BD depression patients induces the development of bipolar depression possibly by modulating aberrant synaptic connectivity and dopamine transmission in the VTA-mPFC pathway, which sheds light on the microbiota-gut-brain mechanisms underlying BD.},
}

@article {pmid41378445,
year = {2025},
author = {Behling, AH and Portlock, T and Ho, D and Wilson, BC and Paramsothy, S and Kamm, MA and Cutfield, WS and Kaakoush, NO and O'Sullivan, JM and Vatanen, T},
title = {Cohort-specific determinants of donor strain engraftment following multi-donor faecal microbiota transplantation in two randomised clinical trials.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2597628},
doi = {10.1080/19490976.2025.2597628},
pmid = {41378445},
issn = {1949-0984},
mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/therapy/microbiology ; Tissue Donors ; Feces/microbiology ; *Obesity/therapy/microbiology ; Bacteria/classification/isolation & purification/genetics ; Randomized Controlled Trials as Topic ; Male ; Female ; Adult ; Middle Aged ; Cohort Studies ; },
abstract = {Disrupted human gut microbiota have been associated with the development of certain disease states, including obesity and ulcerative colitis (UC). Faecal microbiota transplantation (FMT) from healthy donors is a promising avenue to shift the microbiome profile of the recipient towards that of the donor, potentially ameliorating related symptoms. Several recent meta-analyses have investigated the clinical and microbial determinants that influence the retention of transplanted donor microbial strains within the recipient gut microbiome following FMT (i.e. engraftment). However, the specific factors that affect donor strain engraftment in different disease states require further exploration. Here, we perform a strain engraftment analysis on data from two multi-donor FMT clinical trials: the Gut Bugs Trial for obesity and the FOCUS Trial for UC. Using donor strain matching, the donor-recipient pairings of the FOCUS Trial were first predicted in a blinded manner. The subsequent, unblinded, strain engraftment analysis of both datasets highlighted a differential effect of donor-recipient microbiome complementarity on engraftment across the two disease cohorts; greater engraftment efficiency was associated with increased donor-recipient microbial similarity in the FOCUS Trial, and decreased similarity in the Gut Bugs Trial, suggesting that the factors influencing engraftment may differ across disease cohorts.},
}

Humans
*Fecal Microbiota Transplantation
*Gastrointestinal Microbiome
*Colitis, Ulcerative/therapy/microbiology
Tissue Donors
Feces/microbiology
*Obesity/therapy/microbiology
Bacteria/classification/isolation & purification/genetics
Randomized Controlled Trials as Topic
Male
Female
Adult
Middle Aged
Cohort Studies

@article {pmid41378248,
year = {2025},
author = {Abdulaal, R and Afara, I and Harajli, A and Al Mashtoub, E and Tarchichi, A and Hassan, K and Afara, A and Abou Fakher, J and Salhab, S and Fassih, I and Tlais, M},
title = {Gut microbiome and chemotherapy-induced cardiotoxicity: A systematic review of evidence and emerging therapies.},
journal = {World journal of biological chemistry},
volume = {16},
number = {4},
pages = {112221},
pmid = {41378248},
issn = {1949-8454},
abstract = {BACKGROUND: Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy, limiting treatment efficacy and worsening patient outcomes. Recent studies have implicated the gut microbiome and its key metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), in mediating inflammation, oxidative stress, and cardiac damage. The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.

AIM: To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.

METHODS: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2013 and December 2024. Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition, microbial metabolites (e.g., SCFAs, TMAO), or microbiome-targeted interventions. Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction focused on microbiota alterations, mechanistic pathways, cardiac outcomes, and quality assessments using standardized risk-of-bias tools.

RESULTS: Eighteen studies met the inclusion criteria. Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains. This imbalance contributed to gut barrier disruption, systemic inflammation, and oxidative stress, all of which promote myocardial damage. SCFA depletion weakened anti-inflammatory responses, while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction. Preclinical studies showed promising cardioprotective effects from probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, though human data remain limited.

CONCLUSION: Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity. Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury. Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology, warranting further clinical validation through well-designed trials.},
}

@article {pmid41378072,
year = {2025},
author = {Wang, SY and Zhang, MZ and Chen, ZM and Li, ZM and Xie, CY and Yang, GH and Xu, B and Xu, TC},
title = {Intestinal-related substances in obesity regulation: A comprehensive review.},
journal = {World journal of gastrointestinal pharmacology and therapeutics},
volume = {16},
number = {4},
pages = {111082},
pmid = {41378072},
issn = {2150-5349},
abstract = {With the rising global obesity rates, particularly in industrialized nations, obesity has become an increasingly significant public health concern. This review analyzes 132 relevant studies published between 2020 and 2025, with a focus on the role of gut-derived substances in regulating obesity. These include gut hormones [such as glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY, cholecystokinin, and ghrelin], microbial metabolites [such as short-chain fatty acids (SCFA) and indole-3-propionic acid (IPA)], and neurotransmitters (such as serotonin and dopamine).The findings suggest that gut hormones play a crucial role in regulating appetite, glucose metabolism, and energy expenditure, and their dysregulation is closely linked to the development of obesity. Moreover, microbial metabolites like SCFA and IPA are strongly associated with metabolic health and significantly influence obesity-related mechanisms. This review also explores emerging therapeutic strategies, including GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, modulation of the gut microbiota, and fecal microbiota transplantation, all of which demonstrate promising potential in obesity management. However, challenges remain in optimizing these interventions, mitigating adverse effects, and establishing regulatory standards for microbiota-based therapies. Future research should aim to develop personalized, multi-targeted approaches to more effectively combat obesity and its associated metabolic disorders.},
}

@article {pmid41378067,
year = {2025},
author = {Vargas-Beltran, AM and Mialma-Omana, SJ and Vivanco-Tellez, DO},
title = {Targeting gut microbiota in liver disease: A pharmacological approach for hepatic encephalopathy and beyond.},
journal = {World journal of gastrointestinal pharmacology and therapeutics},
volume = {16},
number = {4},
pages = {110271},
pmid = {41378067},
issn = {2150-5349},
abstract = {The gut microbiota plays a pivotal role in the pathogenesis of liver diseases, particularly hepatic encephalopathy (HE), in which dysbiosis contributes to ammonia production, systemic inflammation, and neurocognitive dysfunction. Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity. This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease, focusing on traditional approaches such as non-absorbable disaccharides (lactulose, lactitol), antibiotics (rifaximin), and probiotics as well as novel interventions, including postbiotics, synbiotics, and fecal microbiota transplantation. Additionally, bile acid modulators, short-chain fatty acid derivatives, and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis. We also discussed the implications of gut microbiota modulation in conditions beyond HE, such as metabolic dysfunction-associated steatotic liver disease and cirrhosis. By integrating gut microbiota-targeted therapies into liver disease management, we may develop more effective, personalized approaches to improve patient outcomes and reduce complications.},
}

@article {pmid41377642,
year = {2025},
author = {Edpuganti, S and Subhash, S and Subrahmaniyan, SL and Latheef, S and Albarari, SS},
title = {Gut Microbiome and Cardiovascular Health: Mechanisms, Therapeutic Potential and Future Directions.},
journal = {Heart international},
volume = {19},
number = {2},
pages = {12-20},
pmid = {41377642},
issn = {2036-2579},
abstract = {BACKGROUND: The gut microbiome has a crucial role in host metabolism and immune regulation, and there is growing evidence that dysbiosis may be associated with the pathogenesis of cardiovascular disease (CVD). This narrative review provides an overview of the recent literature on mechanistic connections between the gut and heart, as well as on the therapeutic strategies and research gaps in the gut-heart axis.

METHODS: We conducted a systematic literature search on PubMed and Embase databases with MeSH and keyword terms: 'gut microbiome', 'cardiovascular disease', 'TMAO', 'short-chain fatty acids', 'probiotics' and 'faecal microbiota transplantation'. We considered human and relevant animal studies focusing on mechanistic pathways or microbiome treatments and excluded editorials, small (less than 10 subjects) case series and articles not published in the English language.

RESULTS: Key microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), contribute to atherogenesis, blood pressure and myocardial inflammation. Dysbiosis-induced barrier dysfunction and disturbed bile acid signalling also serve as the mediators of cardiac remodelling. Dietary fibre, probiotics/prebiotics, postbiotics and faecal microbiota transplantation are emerging interventions for the modulation of CVD risk. Nevertheless, most result from observational studies, whilst such are heterogeneous in sequencing platforms and too small to draw any definitive conclusions.

CONCLUSION: The modulation of gut microbiome might be a new target for CVD prevention and treatment. Large-scale, standardized randomized trials with hard cardiovascular endpoints, as well as integrated multi-omics profiling, will be required to validate microbial biomarkers and to optimize microbiome-based interventions.},
}

@article {pmid41377546,
year = {2025},
author = {Wang, JDJ and Suan, E and Li, SS and Shelat, VG},
title = {Sepsis and the diverse organ-gastrointestinal tract axis.},
journal = {World journal of critical care medicine},
volume = {14},
number = {4},
pages = {105547},
pmid = {41377546},
issn = {2220-3141},
abstract = {Sepsis remains a leading cause of morbidity and mortality worldwide, driven by a dysregulated host immune response to infection that culminates in multi-organ dysfunction. Recent advances highlight the gut microbiota's pivotal role in modulating immune responses and influencing the pathophysiology of sepsis through the organ-gastrointestinal tract axis. This review synthesizes current evidence on the bidirectional interplay between gut dysbiosis and the dysfunction of major organ systems-liver, lungs, kidneys, brain, and heart-during sepsis. We explore how gut-derived factors such as microbial translocation, endotoxins, and altered metabolite production exacerbate systemic inflammation and organ injury. In particular, we emphasize the roles of short-chain fatty acids, uremic toxins, bile acids, and trimethylamine-N-oxide in mediating immune dysfunction across the gut-organ axes. Therapeutic strategies targeting the gut microbiota- including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation- show promise in preclinical and early clinical settings. However, challenges related to patient heterogeneity, safety, and the lack of precise biomarkers persist. This review consolidates disparate findings to underscore the gut as a central modulator in sepsis and advocates for microbiota-based interventions as adjunctive therapies in sepsis management.},
}

@article {pmid41377246,
year = {2025},
author = {Singh, PK and Rathi, D and Shweliya, MA and Farooq, A and Anfaal, Z and Saleem, NUA and Hamza, M and Qadri, M and Rath, S and Hemida, MF and Rani, H and Mahgoub, AMA and Wazir, HU},
title = {The interplay of the microbiome and breast cancer: beyond the gut: a narrative review.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {12},
pages = {8496-8507},
pmid = {41377246},
issn = {2049-0801},
abstract = {Breast cancer remains a leading cause of morbidity and mortality among women worldwide, with emerging evidence underscoring the microbiota's pivotal role in its etiology, progression, and therapeutic response. This narrative review synthesizes the intricate interplay between the breast tissue, skin, and lung microbiomes in breast cancer pathogenesis, with particular emphasis on inflammatory breast cancer (IBC) and metastatic dissemination. The healthy breast microbiome, dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes, maintains tissue homeostasis through pH regulation, metabolite production, and immune modulation. Dysbiosis disrupts this equilibrium, fostering carcinogenesis via chronic inflammation, estrogen deconjugation, and DNA damage-induced genomic instability, with subtype-specific microbial signatures influencing tumor growth and therapy resistance. In IBC, skin microbiome alterations characterized by overgrowth of pathogens like Pseudomonas aeruginosa and Staphylococcus aureus exacerbate inflammation, epithelial-mesenchymal transition (EMT), and lymphatic invasion, while promoting a pro-tumorigenic microenvironment enriched in regulatory T cells and M2 macrophages. Concurrently, lung microbiota dysbiosis impairs immune surveillance, remodels the extracellular matrix, and facilitates metastatic seeding through neutrophil extracellular traps and cytokine storms. Cross-talk among these microbiomes amplifies systemic effects, highlighting their synergistic contributions to disease aggressiveness. Advanced analytical techniques, including 16S rRNA sequencing, metagenomics, and metabolomics, offer promising microbial biomarkers for early detection and risk stratification. By elucidating these host-microbe dynamics, this review advocates for microbiome-centric interventionssuch as probiotics, fecal microbiota transplantation, and targeted antimicrobials to enhance precision diagnostics and therapies, ultimately improving outcomes in breast cancer management.},
}

@article {pmid41375654,
year = {2025},
author = {Soares Ferreira Junior, A and Amanda Niz Alvarez, D and da Silva Souza, L and Linares Silva, N and Dias Machado, L and Yoshio Hirai, W and Mesquita Ciconelli, R and Piccolo Feliciano, JV and Colturato, I and Maurício Navarro Barros, G and Scheinberg, P and Chao, NJA and Lelis Vilela de Oliveira, G},
title = {A Distinct Intestinal Domination Fingerprint in Patients Undergoing Allo-HSCT: Dynamics, Predictors and Implications on Clinical Outcomes.},
journal = {Journal of clinical medicine},
volume = {14},
number = {23},
pages = {},
doi = {10.3390/jcm14238351},
pmid = {41375654},
issn = {2077-0383},
support = {#2022/12989-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2023/08142-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2024/02936-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2023/12271-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #313190/2021-6//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
abstract = {Background: Although Enterococcus domination has been extensively evaluated in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the prevalence and clinical implications of other dominant genera remain poorly understood. Objective: In this study, we sought to determine the dynamics, predictors and clinical implications of intestinal domination in Brazilian patients undergoing allo-HSCT. Methods: In a prospective study of four Brazilian centers, fecal specimens were collected longitudinally prior to allo-HSCT until six months post-transplantation. To identify intestinal domination, we performed 16S rRNA gene sequencing using the Illumina platform. We then evaluated the impact of intestinal domination on overall survival and acute Graft-versus-Host-Disease (aGvHD) incidence. Finally, to identify predictors of intestinal domination, we performed a logistic regression model. Results: A total of 192 fecal specimens were collected from 69 patients. No significant changes in alpha or beta diversity were observed over the course of allo-HSCT. Among the 192 specimens, 131 (68%) presented intestinal domination. The top four dominant genera were Bacteroides, Akkermansia, Phascolarctobacterium, and Escherichia-Shigella. No significant associations were found between domination by these genera and either overall survival or aGvHD incidence. Furthermore, no patient-level characteristics, including age, sex, underlying disease, conditioning regimen, or stem cell source, reliably predicted intestinal domination. Conclusions: Our findings reveal a unique intestinal domination fingerprint in Brazilian patients and highlight the importance of geographic context in interpreting microbiota-outcome associations in allo-HSCT settings.},
}

@article {pmid41375540,
year = {2025},
author = {Schank, N and Cottone, A and Wulf, M and Seiter, K and Thomas, B and Miller, LMJ and Anderson, SL and Sahyoun, A and Abidi, AH and Kassan, M and Verma, A},
title = {The Role of Short-Chain Fatty Acids (SCFAs) in Colic and Anti-Inflammatory Pathways in Horses.},
journal = {Animals : an open access journal from MDPI},
volume = {15},
number = {23},
pages = {},
doi = {10.3390/ani15233482},
pmid = {41375540},
issn = {2076-2615},
abstract = {Equine colic remains a prevalent and potentially life-threatening condition with multifactorial origins, including dietary imbalances, stress, and microbial dysbiosis. Central to equine gut health is the production of short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, generated through microbial fermentation of dietary fibers in the hindgut. These metabolites not only serve as vital energy sources but also play crucial roles in maintaining intestinal barrier integrity, modulating motility, and suppressing inflammation. This review explores the role of SCFAs in equine gastrointestinal health, with particular emphasis on their anti-inflammatory effects and potential to prevent or mitigate colic. We examine how SCFAs interact with immune pathways, via G-protein-coupled receptors and regulatory T-cell promotion, to reduce pro-inflammatory cytokines such as TNF-α and IL-6. Evidence suggests that dietary shifts toward high-starch or low-fiber intake can reduce SCFA production, contributing to microbial imbalance, increased gut permeability, and systemic inflammation, all hallmarks of colic pathophysiology. Strategies to enhance SCFA levels, including high-forage diets, targeted prebiotic and probiotic supplementation, and emerging approaches like fecal microbiota transplantation, are discussed. Despite promising findings, significant gaps remain in equine-specific research, highlighting the need for longitudinal and mechanistic studies. Understanding and harnessing the therapeutic potential of SCFAs could pave the way for novel, microbiome-based interventions in colic prevention and treatment.},
}

@article {pmid41374078,
year = {2025},
author = {Biscaglia, G and Gentile, A and Parente, P and Calvo, A and Fontana, R and Continisio, A and Di Brina, ALP and Ciardiello, D and McIlwain, G and Latiano, A and Perri, F and Palmieri, O},
title = {Inflammatory Bowel Disease, Gastrointestinal Graft-Versus-Host Disease and Immune Checkpoint Inhibitors Induced Colitis: Similar Diseases to Treat with Fecal Microbiota Transplantation.},
journal = {Nutrients},
volume = {17},
number = {23},
pages = {},
doi = {10.3390/nu17233788},
pmid = {41374078},
issn = {2072-6643},
support = {n/a//This research was funded by the Italian Ministry of Health (Ricerca Corrente) and 5 per mille/ ; },
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/adverse effects ; *Graft vs Host Disease/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis/therapy/chemically induced ; Gastrointestinal Microbiome ; },
abstract = {Fecal microbiota transplantation (FMT) is a therapeutic strategy designed to modify and enrich the recipient's gut microbiota by administering processed donor stool, with the goal of treating dysbiosis and related conditions. In 2013, the United States Food and Drug Administration (FDA) approved FMT for recurrent Clostridioides difficile infection (rCDI). Since then, its use has been proposed and investigated in several other disorders characterized by gut microbiota imbalance and altered host-microbiota interactions, including inflammatory bowel disease (IBD), immune checkpoint inhibitor-induced colitis (ICI-iC), and gastrointestinal graft-versus-host disease (GI-GVHD). This review aims to highlight the commonalities among these conditions, the pathophysiological mechanisms that support the rationale for FMT, and emerging evidence from clinical studies. Although available studies are heterogeneous, FMT is a rapidly evolving field of research with promising potential to treat IBD and improve outcomes following oncological immunotherapy and allogenic stem cell transplantation. With further validation, FMT could become an important approach in managing immune-mediated gastrointestinal diseases.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Immune Checkpoint Inhibitors/adverse effects
*Graft vs Host Disease/therapy/microbiology
*Inflammatory Bowel Diseases/therapy/microbiology
*Colitis/therapy/chemically induced
Gastrointestinal Microbiome

@article {pmid41373570,
year = {2025},
author = {Mashal, R and Al-Muhanna, A and Khader, S and Khudair, A and Khudair, A and Butler, AE},
title = {The Role of the Gut Microbiome in Type 2 Diabetes Mellitus.},
journal = {International journal of molecular sciences},
volume = {26},
number = {23},
pages = {},
doi = {10.3390/ijms262311412},
pmid = {41373570},
issn = {1422-0067},
mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/therapy ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Dysbiosis/microbiology ; Animals ; Fecal Microbiota Transplantation ; Prebiotics ; },
abstract = {The gastrointestinal tract in humans hosts trillions of microorganisms, collectively termed the gut microbiota, which perform essential physiological processes and roles, including nutrient metabolism and immunomodulation. Influenced by genetics, age, diet, medication, and the environment, the disruption of this system leads to dysbiosis, which has been linked to a range of diseases, notably type 2 diabetes mellitus (T2DM). As the global prevalence of T2DM continues to trend upwards, research investigating and highlighting the influence the gut microbiome exerts on this disease is warranted. The literature was examined regarding microbial metabolites and metabolic signaling pathways, as well as interventions relating to diet, prebiotics, probiotics, pharmacological agents, and fecal microbiota transplantation (FMT). The gut microbiome, through its effects on insulin resistance, inflammation, bile acid signaling, and glucose-lipid metabolism, impacts the development and progression of T2DM. Furthermore, patients with T2DM have demonstrated reduced microbial diversity, depletion of butyrate-producing bacteria, and an increase in pathogenic species. Interventions including high-fiber diets, metformin, probiotics, and FMT were shown to enrich beneficial microbes and improve metabolic outcomes. Targeted modulation of the microbiome, such as through next-generation probiotics and CRISPR-based therapies, may enhance metabolic control in the context of the future of personalized medicine. This review investigates the intricate relationship between the gut microbiome and T2DM, emphasizing its role in disease pathogenesis, the factors that may impact the microbiome in these patients, as well as therapeutic approaches toward its management.},
}

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

@article {pmid41372103,
year = {2025},
author = {Lee, YT and Akan, A and Önel, DB and Medawar, E and Jensen, DEA and Villringer, A and Witte, AV},
title = {Impacts of Lifestyle and Microbiota-Targeted Interventions for Overweight and Obesity on the Human Gut Microbiome: A Systematic Review.},
journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity},
volume = {},
number = {},
pages = {e70037},
doi = {10.1111/obr.70037},
pmid = {41372103},
issn = {1467-789X},
support = {209933838//German Research Foundation (DFG)/ ; WI 3342/3-1//German Research Foundation (DFG)/ ; //Max Planck Society/ ; },
abstract = {Obesity is intricately associated with the gut microbiome, and emerging research suggests that lifestyle interventions, such as dietary changes and active lifestyle, can significantly affect the composition and function of the gut microbiome. However, evidence demonstrating a causal link between these changes and long-term weight loss or metabolic improvements remains limited. This systematic review investigates how overweight- and obesity-targeted interventions, such as dietary modifications, physical activity, supplementation with prebiotics and probiotics, and fecal microbiota transplantation (FMT), manipulate gut microbiome diversity and composition, major metabolites, and weight status. We conducted a systematic literature search and included 87 out of 255 randomized clinical trials with 6086 adults aged 18-84 with a BMI ≥ 25 kg/m[2]. The quality of the included RCTs ranged from very low to moderate risk of bias. Most interventions did not cause any significant changes in microbial alpha or beta diversity, however, positive associations between prebiotic consumption and abundance of Actinobacteria and Bifidobacterium were observed, and intake of probiotics was related to increased levels of Lactobacillus and reduced body weight and body fat. We did not observe strong evidence for associations between SCFA levels, gut microbiome, and obesity. Overall, diversity and heterogeneity in reported outcomes, both in methods and results, were large. Taken together, our findings suggest that overweight- and obesity-targeted dietary interventions of at least 4 weeks, particularly those involving prebiotics and probiotics, have the potential to beneficially alter the gut microbiome, although standardized protocols and harmonized reporting are needed to confirm this through meta-analysis.},
}

@article {pmid41371856,
year = {2026},
author = {Na, C and Shi, X and Fu, J and Li, J and Jiang, H and Guo, Z and Lai, H and Zhang, Z and Zhao, L and Yuan, Q and Zhang, B},
title = {Pectic polysaccharides from Mongolian medicinal Hypecoum leptocarpum: Structure and ulcerative colitis amelioration via gut microbiota and intestinal inflammation regulation.},
journal = {Carbohydrate polymers},
volume = {374},
number = {},
pages = {124717},
doi = {10.1016/j.carbpol.2025.124717},
pmid = {41371856},
issn = {1879-1344},
abstract = {Ulcerative colitis (UC) poses a global health burden due to its refractoriness. Our previous study demonstrated that Hypecoum leptocarpum (H. leptocarpum) crude polysaccharides mitigate UC-related intestinal inflammation. In this study, we extracted, purified, and characterized a pectic polysaccharide (HLP-4-2, 19.7 kDa) from H. leptocarpum, which contained homogalacturonan (HG) and rhamnogalacturonan-I (RG-I). Specifically, RG-I comprises a repeating disaccharide unit of 1,4-α-GalpA and 1,2-α-Rhap (with arabinogalactan branches), whereas HG has partially methyl-esterified GalA residues. In DSS-induced UC mice, HLP-4-2 alleviated disease symptoms in a dose-dependent manner, as evidenced by a reduced disease activity index (DAI), restored colon length, and decreased spleen index. Mechanistically, HLP-4-2 modulated gut microbiota by promoting growth of short-chain fatty acid (SCFA)-producing bacteria (e.g., Prevotella) and reducing abundance of pathogenic bacteria (e.g., Klebsiella). This microbial shift elevated SCFA levels (particularly propionic and isobutyric acids) and reduced isocaproic acid levels. These changes may, in turn, strengthen the intestinal barrier by enhancing mucin secretion, preserving goblet cells, and reducing inflammation via downregulating proinflammatory cytokines. Fecal microbiota transplantation (FMT) experiments confirmed that these microbial changes contributed to HLP-4-2's therapeutic effects. These findings endorse the traditional use of H. leptocarpum for inflammation and indicate HLP-4-2 as a potential treatment for ulcerative colitis.},
}

@article {pmid41370178,
year = {2025},
author = {Peto, L and Fawcett, N and Kamfose, MM and Scarborough, C and Peniket, A and Danby, R and Peto, TEA and Crook, DW and Llewelyn, MJ and Walker, AS},
title = {The impact of different antimicrobial exposures on the gut microbiome in the ARMORD observational study.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
doi = {10.7554/eLife.97751},
pmid = {41370178},
issn = {2050-084X},
support = {NIHR200915//National Institute for Health and Care Research/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Male ; Female ; Adult ; Cross-Sectional Studies ; Middle Aged ; Aged ; *Anti-Bacterial Agents/pharmacology ; *Anti-Infective Agents/pharmacology ; Feces/microbiology ; Metagenomics ; United Kingdom ; *Bacteria/drug effects/classification/genetics ; Young Adult ; },
abstract = {Better metrics to compare the impact of different antimicrobials on the gut microbiome would aid efforts to control antimicrobial resistance (AMR). The Antibiotic Resistance in the Microbiome - Oxford (ARMORD) study recruited inpatients, outpatients, and healthy volunteers in Oxfordshire, UK, who provided stool samples for metagenomic sequencing. Data on previous antimicrobial use and potential confounders were recorded. Exposures to each antimicrobial were considered as factors in a multivariable linear regression, also adjusted for demographics, with separate analyses for those contributing samples cross-sectionally or longitudinally. Outcomes were Shannon diversity and relative abundance of specific bacterial taxa (Enterobacteriaceae, Enterococcus, and major anaerobic groups) and antimicrobial resistance genes (targeting beta-lactams, tetracyclines, aminoglycosides, macrolides, and glycopeptides). 225 adults were included in the cross-sectional analysis, and a subset of 79 patients undergoing haematopoietic cell transplant provided serial samples for longitudinal analysis. Results were largely consistent between the two sampling frames. Recent use of piperacillin-tazobactam, meropenem, intravenous co-amoxiclav, and clindamycin was associated with large reductions in microbiome diversity and reduced abundance of anaerobes. Exposure to piperacillin-tazobactam and meropenem was associated with a decreased abundance of Enterobacteriaceae and an increased abundance of Enterococcus and major AMR genes, but there was no evidence that these antibiotics had a greater impact on microbiome diversity than iv co-amoxiclav or oral clindamycin. In contrast, co-trimoxazole, doxycycline, antifungals, and antivirals had less impact on microbiome diversity and selection of AMR genes. Simultaneous estimation of the impact of over 20 antimicrobials on the gut microbiome and AMR gene abundance highlighted important differences between individual drugs. Some drugs in the WHO Access group (co-amoxiclav, clindamycin) had similar magnitude impact on microbiome diversity to those in the Watch group (meropenem, piperacillin-tazobactam) with potential implications for acquisition of resistant organisms. Metagenomic sequencing can be used to compare the impact of different antimicrobial agents and treatment strategies on the commensal flora.},
}

Humans
*Gastrointestinal Microbiome/drug effects
Male
Female
Adult
Cross-Sectional Studies
Middle Aged
Aged
*Anti-Bacterial Agents/pharmacology
*Anti-Infective Agents/pharmacology
Feces/microbiology
Metagenomics
United Kingdom
*Bacteria/drug effects/classification/genetics
Young Adult

@article {pmid41370004,
year = {2025},
author = {Syed, S and Moayyedi, P and Kao, D and Patel, J and Marshall, JK and Surette, M and Narula, N},
title = {Combination Therapy With Fecal Microbiota Transplantation and Vedolizumab for Induction of Remission in Ulcerative Colitis: An Open-Label Pilot Study.},
journal = {Inflammatory bowel diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/ibd/izaf284},
pmid = {41370004},
issn = {1536-4844},
support = {//Takeda Canada/ ; },
}

@article {pmid41369516,
year = {2025},
author = {Yang, J and Yu, J and Chen, Y and Xu, A and Yang, C and Li, J and Wu, F and Li, X and Bi, J and Xiang, B and Jiang, K},
title = {Hyperoside, a dietary flavonoid, protects against endometritis via gut microbiota-dependent production of hydroxyphenyllactic acid and the gut-uterus axis.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo04275e},
pmid = {41369516},
issn = {2042-650X},
abstract = {Endometritis, primarily caused by Escherichia coli (E. coli) infection, poses significant therapeutic challenges due to rising antibiotic resistance. The associated pro-inflammatory cytokines cause persistent endometrial damage, thereby leading to infertility, pregnancy loss, and other gynecological complications, which impose substantial long-term medical and socioeconomic burdens. Hyperoside, a flavonol glycoside abundant in various common fruits (e.g., hawthorn) and vegetables, exhibits significant anti-inflammatory activity, highlighting its potential as a functional food or nutraceutical. Our present study firstly demonstrated that hyperoside could alleviate E. coli-induced endometritis in mice through a gut-uterus axis mechanism. Specifically, hyperoside remodeled the gut microbiota by enriching beneficial genera, such as Lactobacillus and Prevotella, which subsequently elevated the production of the metabolite hydroxyphenyllactic acid (HPLA). Crucially, antibiotic treatment and fecal microbiota transplantation (FMT) experiments further confirmed that gut microbiota restructuring was essential for the anti-endometritic effect of hyperoside. Mechanistically, HPLA enters systemic circulation and targets uterine tissue, where it is directly bound to TLR4 to suppress the activation of the TLR4/NF-κB pathway and then the release of inflammatory cytokines. The present study provides the first systematic evidence of the gut-uterus axis, establishing microbiota-derived HPLA as a key effector against E. coli-induced endometritis, offering a novel nutritional intervention strategy for inflammatory reproductive disorders.},
}

@article {pmid41368686,
year = {2025},
author = {Wu, J and Zheng, W and Ding, X and Jin, Q and Ding, M},
title = {Obesity-induced gut microbiota transplantation promotes the occurrence and development of hepatocellular carcinoma.},
journal = {Future science OA},
volume = {11},
number = {1},
pages = {2599729},
doi = {10.1080/20565623.2025.2599729},
pmid = {41368686},
issn = {2056-5623},
abstract = {OBJECTIVE: Obesity is a recognized risk factor for hepatocellular carcinoma (HCC), yet the causal role of obesity-remodeled gut microbiota remains poorly defined. This study aims to investigate the direct impact of obesity-related gut microbiota on the development of hepatocellular carcinoma.

METHODS: C57BL/6J mice were fed a high-fat diet (HFD) to establish obesity. Fecal microbiota from HFD or normal-chow diet (NCD) mice was transplanted into DEN-initiated recipients. Tumor burden was assessed by incidence, multiplicity, and size. Histomorphology and biochemical methods were employed to assess liver injury, inflammation, fibrosis, lipid metabolism, and the potential signaling pathways involved in these events.

RESULTS: The gut microbiota of obese mice significantly promoted the incidence of HCC, and increased tumor number, and size spectrum. Specifically, obesity-related gut microbiota significantly aggravated hepatocarcinogenesis (increasing GPC3, GP73, AFP, and N-cadherin, and decreasing E-cadherin), pro-inflammatory cytokine surge (increasing IL-6, IL-1β, IL-17, and TNF-α), and fibrotic activation (increasing α-SMA, TGF-β, and Col1a1) were observed. Mechanistically, obesity-FMT dysregulated lipid metabolism (increasing free fatty acids, total cholesterol, and triglycerides) and activated TLR4-NF-κB and mTOR pathways.

CONCLUSION: Our findings suggest that gut microbiota from obese donors directly promotes HCC progression via TLR4-NF-κB/mTOR-driven inflammation, fibrosis, and metabolic dysregulation, offering novel targets for microbiota-based interventions in obesity-associated liver cancer.},
}

@article {pmid41368634,
year = {2025},
author = {Shen, X and Li, Y and Wang, D and Sun, K},
title = {The gut microbiota and its metabolites: novel therapeutic targets for inflammatory bowel disease.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1690279},
pmid = {41368634},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/therapy/microbiology/metabolism/immunology ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; Bile Acids and Salts/metabolism ; Dysbiosis/therapy ; Fatty Acids, Volatile/metabolism ; Tryptophan/metabolism ; },
abstract = {Inflammatory bowel disease (IBD) pathogenesis is critically influenced by gut microbiota dysbiosis and perturbations in associated metabolites. This review outlines current IBD diagnostic and therapeutic paradigms, highlighting the persistent focus on the management of inflammatory symptoms and the absence of curative interventions. We elucidate the mechanistic links between gut microbiota dysregulation and IBD progression, with an emphasis on the immunomodulatory functions of microbial metabolites-specifically short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp) metabolism-in maintaining intestinal barrier integrity and attenuating inflammation. Furthermore, we evaluate microbiota-targeted therapeutic strategies, including probiotics, fecal microbiota transplantation (FMT), and metabolite-based interventions, as novel approaches for IBD management. This synthesis aims to inform future therapeutic development and accelerate the clinical translation of microbiota-modulating regimens.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Inflammatory Bowel Diseases/therapy/microbiology/metabolism/immunology
Fecal Microbiota Transplantation
Animals
Probiotics/therapeutic use
Bile Acids and Salts/metabolism
Dysbiosis/therapy
Fatty Acids, Volatile/metabolism
Tryptophan/metabolism

@article {pmid41368309,
year = {2025},
author = {Liu, L and Yang, L and Zhang, H and Li, H and Shang, T and Liu, L},
title = {Lung cancer and the Gut-microbiota-lung Axis: emerging evidence and potential clinical implications.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1655780},
pmid = {41368309},
issn = {2296-858X},
abstract = {Lung cancer remains the leading cause of cancer-related deaths globally, with a 5-years survival rate of only around 20%. Merging cohort and Mendelian-randomization studies indicate that gut dysbiosis is associated with-though not yet proven to cause-an elevated risk and worse prognosis of non-small-cell lung cancer. Lower fecal abundance of butyrate producers such as Faecalibacterium prausnitzii and expansion of Enterobacteriaceae correlate with reduced systemic CD8 + T-cell infiltration and shorter progression-free survival during immune-checkpoint blockade. Antibiotic exposure within 30 days before anti-PD-1 initiation is consistently linked to diminished objective response and overall survival in retrospective cohorts, whereas supplementation with butyrogenic probiotics or fecal microbiota transplantation from responders restores therapeutic efficacy in pre-clinical models. This review integrates epidemiological, mechanistic and clinical data to clarify the current evidence, identify gaps and outline the steps needed to translate gut-lung-axis research into safe, effective adjunctive therapies for patients with lung cancer.},
}

@article {pmid41367416,
year = {2025},
author = {Liu, SH and Yang, XF and Liang, L and Song, BB and Song, XM and Yang, YJ and Alhoot, MA},
title = {Regulatory mechanisms of the gut microbiota-short chain fatty acids signaling axis in slow transit constipation and progress in multi-target interventions.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1689597},
pmid = {41367416},
issn = {1664-302X},
abstract = {Slow-transit constipation (STC) is an increasingly prevalent disorder that imposes a substantial health and economic burden. Mounting evidence highlights the "gut microbiota-short-chain fatty acid (SCFA)-motility" axis as a central pathophysiological link between dysbiosis and impaired colonic transit. This review synthesizes current knowledge of how SCFAs, especially acetate, propionate and butyrate, shape motility through serotonergic signaling, enteric nervous system modulation, epithelial barrier integrity and immune regulation. Particular attention is devoted to the biased-signaling properties of the SCFA receptors FFAR2 and FFAR3 (free fatty acid receptors 2 and 3, respectively), including emerging data on their heterodimerization. The article then appraises recent randomized controlled trials and meta-analyses of multi-target interventions (dietary fibers, synbiotics, postbiotics, fecal microbiota transplantation, phytochemicals, and small-molecule FFAR agonists) highlighting their efficacy, safety, and translational hurdles. Finally, the authors propose a precision-medicine framework that integrates multi-omics microbiome profiling, metabolomics, and host genetics to enable phenotype-stratified therapy. Key research gaps include limited long-term safety data, heterogeneous human cohorts and the need for large multicenter trials and machine-learning-guided responder prediction. Collectively, the review provides a roadmap for shifting STC management from symptom control to mechanism-based, personalized care.},
}

@article {pmid41361827,
year = {2025},
author = {Tao, M and Wu, T and Li, S and Tan, Y and Zhou, X and Chen, Y and Huang, L and Wang, W and Li, S and Wang, L and Luo, Z and Wang, Y and Ling, K and Liang, Z},
title = {Intratumoral Collinsella aerofaciens exhibits antitumor activity in endometrial carcinoma through activation of the p53 signaling pathway.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-025-07543-7},
pmid = {41361827},
issn = {1479-5876},
support = {2019YFC1005202//National Key Research and Development Program of China/ ; },
abstract = {BACKGROUND: The intratumoral microbiota plays dual roles in cancer progression and suppression, but its composition and functional mechanisms in endometrial carcinoma (EC) remain incompletely defined. This study aimed to characterize the EC intratumoral microbiome, elucidate microbial spatial localization, and identify bacteria with tumor-suppressive properties.

METHODS: Tumor and adjacent normal tissues from patients with EC were analyzed using 5R 16S rRNA sequencing to profile microbial communities, with fluorescence in situ hybridization (FISH) validating bacterial localization. Spatial transcriptomics (ST), single-cell RNA sequencing (scRNA-seq), and FISH were integrated to map microbiota-niche cell interactions. RNA sequencing was performed on EC cells treated with bacterial supernatant. Fecal microbiota transplantation (FMT) from EC patients to mice was used to assess gut-tumor microbial crosstalk.

RESULTS: Collinsella aerofaciens (C. aerofaciens), Haloamaerobium gallinarum, and Massilia oculi were enriched in adjacent normal tissues, while Bacteroides vulgatus (B. vulgatus) and Delfia tsuruhatensis dominated tumor tissues. Tumors exhibited reduced microbial richness versus normal tissues. C. aerofaciens localized predominantly to smooth muscle cells and modulated the tumor microenvironment, as revealed by FISH and ST-scRNA-seq integration. RNA sequencing suggested that C. aerofaciens suppressed EC progression by activating the p53 signaling pathway. FMT experiments demonstrated gut microbiota-driven remodeling of the tumor microbiome.

CONCLUSIONS: This study identifies C. aerofaciens as a novel tumor-suppressive bacterium in EC, with mechanistic evidence linking its activity to p53 pathway activation. Gut microbiota modulates intratumoral microbial composition, suggesting potential dual-target therapeutic strategies for EC.},
}

@article {pmid41361755,
year = {2025},
author = {Dong, R and Meng, X and Hu, H and Pan, J and Wang, W},
title = {Integrating gut microbiota and metabolomics in pediatric inflammatory bowel disease: insights into pathogenesis and potential role of precision medicine.},
journal = {European journal of medical research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40001-025-03658-1},
pmid = {41361755},
issn = {2047-783X},
abstract = {Pediatric inflammatory bowel disease (IBD) is a chronic and relapsing disorder with rising global incidence. Gut microbiota dysbiosis and metabolic alterations have been implicated in disease pathogenesis, yet their precise roles in pediatric IBD remain incompletely understood. This review synthesizes current evidence on the interplay between the gut microbiota and metabolomics in pediatric IBD, highlighting their contributions to disease onset, progression, and therapeutic response. We examine changes in microbial composition, alterations in short-chain fatty acid, bile acid, and amino acid metabolism, and their effects on intestinal immunity and barrier function. In addition, we discuss microbiota-based therapies, such as probiotics, prebiotics, and fecal microbiota transplantation, along with the potential of metabolomic profiles for diagnostic and prognostic use. Finally, we emphasize integrating multi-omics approaches to uncover novel therapeutic targets and advance precision medicine strategies in pediatric IBD. A deeper understanding of microbiota-metabolite interactions may pave the way for personalized interventions to improve clinical outcomes in pediatric patients with IBD.},
}

@article {pmid41361135,
year = {2025},
author = {Konturek, PC and Ghopreal, T and Dieterich, W and Zopf, Y},
title = {[Gut-lung axis from a gastroenterological perspective].},
journal = {MMW Fortschritte der Medizin},
volume = {167},
number = {Suppl 6},
pages = {22-26},
doi = {10.1007/s15006-025-5477-3},
pmid = {41361135},
issn = {1613-3560},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Dysbiosis/immunology/therapy ; *Lung/microbiology/immunology ; Fecal Microbiota Transplantation ; *Lung Diseases/microbiology/immunology ; Lung Neoplasms/immunology ; Probiotics/therapeutic use ; },
abstract = {BACKGROUND: The microbiome is unique to each individual. It plays a key role in numerous physiological processes in the body. Intestinal dysbiosis is associated with various diseases.

METHOD: This work provides an overview of the current state of knowledge regarding the role of microbiota in the lungs and the gut-lung axis.

RESULTS AND CONCLUSIONS: Numerous studies have demonstrated a link between respiratory diseases and an altered lung microbiome. Dysbiosis of the gut microbiota influences the lung's immune response via gut-lung axis. Changes in the lung microbiome due to various environmental factors, such as smoking, particulate matter, or air pollution, contribute to lung cancer development. The composition of the gut microbiome influences the response to therapy with immune checkpoint inhibitors. Modulation of the gut microbiota through fecal microbiota transplantation (FMT), diet, prebiotics, probiotics, and synbiotics can positively influence the response to immunotherapy.},
}

Humans
*Gastrointestinal Microbiome/physiology/immunology
Dysbiosis/immunology/therapy
*Lung/microbiology/immunology
Fecal Microbiota Transplantation
*Lung Diseases/microbiology/immunology
Lung Neoplasms/immunology
Probiotics/therapeutic use

@article {pmid41358173,
year = {2025},
author = {Othman, AAA},
title = {From rescue to recovery: Reframing severe alcoholic hepatitis management through 90-day survival.},
journal = {World journal of gastroenterology},
volume = {31},
number = {43},
pages = {113141},
pmid = {41358173},
issn = {2219-2840},
mesh = {Humans ; *Hepatitis, Alcoholic/mortality/therapy/diagnosis ; Treatment Outcome ; Severity of Illness Index ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Adrenal Cortex Hormones/therapeutic use ; Time Factors ; Randomized Controlled Trials as Topic ; },
abstract = {Severe alcoholic hepatitis remains one of hepatology's most urgent challenges, with rapid clinical deterioration and high early mortality. This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al, which redirects attention from short-term endpoints toward 90-day survival, integrating evidence from associated clinical studies. For decades, corticosteroids have been the mainstay of treatment, reducing 28-day mortality but offering limited benefit for three months. The review emphasizes that the most critical threats to recovery, late infections, renal decline, and relapse, often emerge after the first month. By synthesizing recent studies, it highlights promising interventions such as fecal microbiota transplantation (FMT), which improved 90-day survival in a small randomized trial, and granulocyte colony-stimulating factor (G-CSF), which showed a robust survival benefit in a large retrospective cohort, alongside emerging strategies like plasma exchange and targeted biologics. These findings support a shift toward a two-phase care model: Early stabilization followed by recovery consolidation. For clinicians, such a model may help guide treatment decisions, with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders, pending further validation in larger randomized controlled trials. Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission, providing a more realistic measure of therapeutic success in one of hepatology's most unforgiving conditions.},
}

Humans
*Hepatitis, Alcoholic/mortality/therapy/diagnosis
Treatment Outcome
Severity of Illness Index
Fecal Microbiota Transplantation
Granulocyte Colony-Stimulating Factor/therapeutic use
Adrenal Cortex Hormones/therapeutic use
Time Factors
Randomized Controlled Trials as Topic

@article {pmid41357887,
year = {2025},
author = {Peng, Q and Hao, L and Li, S and Yu, F and Li, N and Hu, X},
title = {A critical review of natural products driven correction of bile acid dysregulation: a therapeutic strategy for nonalcoholic fatty liver disease.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1640873},
pmid = {41357887},
issn = {1663-9812},
abstract = {Nonalcoholic fatty liver disease (NAFLD) represents a significant global health challenge. While two drugs (semaglutide, resmetirom) have recently been approved for nonalcoholic steatohepatitis (NASH), their clinical utility is constrained by gastrointestinal side effects, insufficient efficacy against fibrosis, and dose-related adverse events. Similarly, obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with antifibrotic potential, is associated with significant side effects, including severe pruritus. Dysregulation of bile acid (BA) metabolism is a central driver of NAFLD progression, characterized by imbalances in synthesis, impaired enterohepatic circulation, and aberrant nuclear receptor signaling. Certain hydrophobic BAs contribute to hepatocyte apoptosis, oxidative stress, and inflammation, thereby exacerbating liver injury. Targeting BA homeostasis is thus a promising therapeutic strategy, with natural products emerging as attractive candidates due to their multi-target actions and favorable safety profiles. This review summarizes 10 major classes of natural products, including traditional Chinese medicine (TCM) formulas, flavonoids, saccharides, saponins, alkaloids, curcuminoids, lignans, iridoid glycosides, sterols/terpenoids, and phenolic acids/other phenolics, that alleviate NAFLD by regulating BA metabolism. These agents modulate BA-sensing receptors, reshape the gut microbiota to optimize BA conversion, and regulate key BA transporters and enzymes. Compared with synthetic drugs, natural products offer broader efficacy, lower toxicity, and greater adaptability to the heterogeneity of NAFLD. However, significant limitations persist. Preclinical studies rely heavily on single-sex rodent models, while clinical evidence remains inconsistent. Crucially, mechanistic causality, such as the interplay between the gut microbiota and BAs, lacks rigorous validation through methods like fecal microbiota transplantation (FMT) or gene knockout studies. Furthermore, challenges in metabolite standardization and dose rationality hinder clinical translation. Future research must prioritize human-relevant models, large-scale randomized controlled trials (RCTs) with histological endpoints, and robust causal validation. By addressing these gaps, natural products targeting BA metabolism hold great promise to complement or replace existing therapies, offering safer and more effective personalized treatments for NAFLD.},
}

@article {pmid41357831,
year = {2025},
author = {Xiao, J and Xia, J and Chen, Z and Zha, W and Xu, T and Chen, X and Yin, X},
title = {Gut microbiota dysbiosis drives stroke-associated pneumonia: mechanisms and targeted therapeutic strategies.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1677744},
pmid = {41357831},
issn = {1662-4548},
abstract = {The gut microbiota has been increasingly recognized as a central regulator of immune function, with growing research highlighting its association with the development of stroke-associated pneumonia (SAP). This review provides an overview of current research on the correlation between SAP and alterations in gut microbial composition and metabolism, with a focus on microbial imbalance, changes in key metabolites, and relevant biological mechanisms. Clinical and preclinical studies consistently report a decline in short-chain fatty acids (SCFAs)-producing bacteria, an increase in potentially harmful microbial species, reduced SCFAs levels, and elevated lipopolysaccharide (LPS) concentrations. These disturbances appear to be associated with SAP progression through the microbiota-gut-brain and microbiota-gut-lung axes by affecting immune regulation and inflammatory responses. The review also examines microbiota-targeted treatment approaches, including dietary modification, antibiotic therapy, probiotics, microbiota-regulating compounds, fecal microbiota transplantation (FMT), and respiratory microbiota transfer. A deeper understanding of how microbial disturbances are correlated with SAP may help explain the increased vulnerability to pulmonary infections following stroke and support the design of more effective, microbiota-based therapeutic strategies.},
}

@article {pmid41356558,
year = {2025},
author = {Wang, H and Yang, F and Gao, Z and Cheng, Z and Liang, X},
title = {The gut-brain axis in Alzheimer's disease: how gut microbiota modulate microglial function.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1704047},
pmid = {41356558},
issn = {2673-6217},
abstract = {Alzheimer's disease (AD) is a complex neurodegenerative disorder that can be caused by multiple factors, such as abnormal amyloid-beta (Aβ) deposition, pathological changes in Tau protein, lipid metabolism disorders, and oxidative stress. Recent studies have revealed the potential link between gut microbiota and AD, particularly the impact of gut microbiota and its derivatives on microglia. As immune cells in the central nervous system (CNS), microglia are involved in neuroinflammation and the regulation of cognitive function. Research indicates that the dysregulation of gut microbiota may affect the phenotype and function of microglia through various mechanisms, including direct metabolite action and indirect immune and neurotransmitter regulation. This article reviews the direct and indirect effects of gut microbiota and its derivatives on microglia, explores their role in the pathogenesis of AD, and discusses therapeutic strategies based on gut microbiota, such as dietary regulation, probiotics, fecal microbiota transplantation, and traditional Chinese medicine. Although existing studies have shown the potential of these interventions, further research is needed to completely understand their application in the treatment of AD.},
}

@article {pmid41356485,
year = {2025},
author = {Bai, B and Ma, J and Xu, W and Chen, X and Chen, X and Lv, C and Su, W and Li, Y and Sun, H and Zhang, B and Xiang, D and Li, Z and Wu, Y and Sun, J and Yin, M},
title = {Gut microbiota and colorectal cancer: mechanistic insights, diagnostic advances, and microbiome-based therapeutic strategies.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1699893},
pmid = {41356485},
issn = {1664-302X},
abstract = {Colorectal cancer (CRC) is closely linked to gut microbiota dysbiosis. We synthesize evidence that carcinogenic microbes promote CRC through chronic inflammation, bacterial genotoxins, and metabolic imbalance, highlighting key pathways involving Fusobacterium nucleatum, pks [+] Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF). Building on these mechanisms, we propose a minimal diagnostic signature that integrates multi-omics with targeted qPCR, and a pathway-therapy-microbiome matching framework to guide individualized treatment. Probiotics, fecal microbiota transplantation (FMT), and bacteriophage therapy show promise as adjunctive strategies; however, standardization, safety monitoring, and regulatory readiness remain central hurdles. We advocate a three-step path to clinical implementation-stratified diagnosis, therapy matching, and longitudinal monitoring-supported by spatial multi-omics and AI-driven analytics. This approach aims to operationalize microbiome biology into deployable tools for risk stratification, treatment selection, and surveillance, advancing toward microbiome-informed precision oncology in CRC.},
}

@article {pmid41355913,
year = {2025},
author = {Roganovic, J and Radosevic, M and Dordevic, A},
title = {Role of the gut microbiome in the development and prognosis of pediatric leukemia.},
journal = {World journal of clinical oncology},
volume = {16},
number = {11},
pages = {111419},
pmid = {41355913},
issn = {2218-4333},
abstract = {The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation, both of which are critically involved in the pathogenesis and progression of pediatric leukemias. Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis, marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus. This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation. Chemotherapy significantly alters the gut microbiome, inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts. Specific microbial signatures, such as the enrichment of Bacteroides, correlate with reduced inflammation and improved prognosis, underscoring the gut microbiome's prognostic value. Emerging therapies, including dietary adjustments, probiotics, and fecal gut microbiome transplantation, aim to restore microbial balance and reduce treatment-related complications. Moreover, gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition, paving the way for early diagnosis and tailored preventive strategies. This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias, emphasizing its role as both a therapeutic target and a prognostic biomarker. Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.},
}

@article {pmid41352744,
year = {2025},
author = {Wei, D and Sun, Y and Han, J and Liu, J},
title = {Microbiota and Cancer Immunotherapy: Mechanisms, Clinical Implications, and Precision Therapeutics.},
journal = {Seminars in cancer biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.semcancer.2025.12.002},
pmid = {41352744},
issn = {1096-3650},
abstract = {The microbiome has emerged as a pivotal modulator of cancer immunotherapy, offering novel insights into the efficacy and toxicity of immune checkpoint inhibitors (ICIs). Recent evidence highlights that microbial communities and their metabolites dynamically regulate host immunity by priming dendritic cells, enhancing T-cell infiltration, and reprogramming the tumor microenvironment. Microbiome dysbiosis is implicated in immune-related adverse events (irAEs), underscoring its dual role in therapeutic outcomes. Leveraging these findings, precision microbiome interventions, including fecal microbiota transplantation, engineered probiotics, and dietary modulation, which demonstrate potential to enhance ICIs responsiveness and mitigate irAEs in preclinical and early-phase clinical studies. However, translating these strategies into clinical practice requires rigorous validation through multicenter trials to establish safety, efficacy, and standardized protocols. This review synthesizes current knowledge on the microbiome-immune-oncology axis, with a focus on mechanistic underpinnings, translational challenges, and innovative therapeutic strategies. By integrating microbiome profiling with patient-specific factors, proposing a roadmap for personalized immunotherapy, aligning with the emerging paradigm of precision oncology.},
}

@article {pmid41352125,
year = {2025},
author = {Taki, AG and Shareef, A and Arora, V and Oweis, R and Jyothi, SR and Singh, U and Sahoo, S and Chauhan, AS and Alimova, F and Sameer, HN and Yaseen, A and Athab, ZH and Adil, M},
title = {Unraveling the microbiome's role in breast cancer progression and treatment response.},
journal = {Current problems in cancer},
volume = {60},
number = {},
pages = {101264},
doi = {10.1016/j.currproblcancer.2025.101264},
pmid = {41352125},
issn = {1535-6345},
abstract = {The human microbiome, encompassing microbial communities in the gut and breast tissue, has emerged as a critical modulator of breast cancer (BC) initiation, progression, and treatment response. This review synthesizes current evidence on the microbiome's role in BC, highlighting its influence on tumorigenesis, tumor microenvironment (TME), and therapeutic outcomes. Breast cancer, the most prevalent malignancy among women globally, exhibits significant heterogeneity across its molecular subtype's hormone receptor-positive, HER2-enriched, and triple-negative-each with distinct clinical challenges. Recent studies reveal that microbial dysbiosis in the gut and breast tissue can drive oncogenesis through mechanisms such as immune modulation, estrogen metabolism, and inflammation. Gut microbes, via the "estrobolome," regulate circulating estrogen levels, impacting hormone-driven BC, while breast tissue microbiota contributes to local inflammation and DNA damage, promoting tumor progression. Specific microbial taxa, including Bacillus, Staphylococcus, and Escherichia coli, are enriched in BC patients, whereas beneficial species like Lactobacillus and Bifidobacterium are diminished. The microbiome also influences treatment efficacy, with gut microbial diversity linked to enhanced chemotherapy and immunotherapy responses, while antibiotic-induced dysbiosis may impair outcomes. Emerging research suggests microbiome signatures as potential biomarkers for predicting therapeutic success, with Akkermansia muciniphila and short-chain fatty acids showing promise in enhancing anti-tumor immunity. Probiotics, prebiotics, and fecal microbiota transplantation offerel therapeutic avenues, though challenges such as standardization, interindividual variability, and safety concerns remain. Integrating multi-omics and machine learning could elucidate microbiome-host interactions, paving the way for precision oncology. This review underscores the transformative potential of microbiome-based diagnostics and interventions in improving BC management, emphasizing the need for large-scale, longitudinal studies to validate these findings and address existing research gaps.},
}

@article {pmid41351979,
year = {2025},
author = {Yang, Q and Huo, J and Peng, R and Qiu, S and Li, P and Wei, W and Zhou, J and Tang, Q and Wang, W},
title = {Glycitein in Zhi-Zi-Chi decoction alleviates anxiety via inosine enrichment mediated by Akkermansia muciniphila to regulate MT3-Sema7a interaction.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157622},
doi = {10.1016/j.phymed.2025.157622},
pmid = {41351979},
issn = {1618-095X},
abstract = {BACKGROUND: Zhi-Zi-Chi Decoction (ZZCD) is used for treating emotional disturbances and insomnia. Its potential anti-anxiety efficacy has been proposed, yet the bioactive constituents and underlying mechanisms remain poorly defined.

OBJECTIVE: This study aimed to investigate the anxiolytic effects of ZZCD, identify its active components, and elucidate the mechanisms involved, with particular emphasis on the gut-microbiota-brain axis.

METHODS: The anxiety model was established using the chronic restraint stress (CRS) method. 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) were employed to investigate the role of gut microbiota in the development and treatment of anxiety. N500-targeted metabolomics and RT-qPCR identified key microbial taxa and their functionally relevant metabolites. Key bioactive components of ZZCD were screened through in vitro bacterial co-culture and confirmed by in vivo pharmacological experiments. Molecular mechanisms were further explored via transcriptomics, western blotting, and co-immunoprecipitation.

RESULTS: ZZCD alleviated CRS-induced anxiety behaviors, restored brain neurotransmitter homeostasis, and reduced pro-inflammatory cytokine expression. Mechanistically, its anxiolytic effect was associated with Akkermansia muciniphila (A. muciniphila). A. muciniphila supplementation improved anxiety symptoms and promoted neurotransmitter balance. Targeted metabolomics identified inosine as a key microbial metabolite. Inosine enhanced neuronal activity, restored intestinal barrier integrity, and suppressed hippocampal NLRP3/Caspase-1/IL-18 signaling. Further, -a major isoflavone in ZZCD-was confirmed as a key anxiolytic compound, acting by promoting inosine production from A. muciniphila and regulating Metallothionein3-Sema7a protein interaction in the hippocampus.

CONCLUSION: Glycitein in ZZCD exerts anxiolytic effects by facilitating A. muciniphila -derived inosine production and modulating hippocampal MT3-Sema7a signaling, highlighting a novel microbiota-mediated therapeutic strategy for anxiety.},
}

@article {pmid41351660,
year = {2025},
author = {A, AP and Daksh, R and Dinil, A and B, AC and Nampoothiri, M and Nampoothiri, KM},
title = {Investigations on the Prospects of Using Lactiplantibacillus plantarum to Combat Depression through Gut Microbiota-Brain Axis.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {259},
pmid = {41351660},
issn = {1559-1182},
support = {DBT/2021-22/NIIST/1743//DBT/ ; IF230068//INSPIRE, New Delhi/ ; },
mesh = {*Gastrointestinal Microbiome/physiology/drug effects ; Humans ; *Depression/therapy/microbiology ; *Brain/metabolism ; *Probiotics/therapeutic use/pharmacology ; Animals ; *Lactobacillus plantarum ; },
abstract = {Depression is a common neurological disorder that causes a substantial burden of disease due to higher mortality and prevalence rates. The gut microbiota plays a major role in mood regulation and offers novel insights into the etiology and management of depression. However, gut dysbiosis has a negative impact on mood, cognition, behavior, and brain development. Therefore, approaches to restore the normal gut composition, such as probiotics, prebiotics, and fecal microbiota transplant, may offer novel tactics to improve therapy for depression, among which probiotics have drawn significant attention as a therapeutic intervention. Although there is no consensus on the most effective probiotic strain for treating depression, Lactiplantibacillus plantarum (L. plantarum) has gained considerable prominence due to its therapeutic potential in managing depression. The mechanisms by which L. plantarum regulates depression involve modulating the gut-brain axis through the production of various compounds, including gamma-aminobutyric acid (GABA), tryptophan, lactate, short-chain fatty acids (SCFAs), acetylcholine, and vitamins. This review highlights the antidepressant potential of L. plantarum through modulation of the gut microbiota and explores the possible mechanism of action of L. plantarum and its metabolites, as well as the genetic and epigenetic regulation of host responses and potential microRNA interactions that modulate the gut microbiota. Furthermore, metabolic engineering techniques for the L. plantarum strain, as well as promising strategies for delivering L. plantarum to the brain, have been discussed. A deeper insight into the mechanisms and gut microbiota interventions may provide effective treatment approaches for depression.},
}

*Gastrointestinal Microbiome/physiology/drug effects
Humans
*Depression/therapy/microbiology
*Brain/metabolism
*Probiotics/therapeutic use/pharmacology
Animals
*Lactobacillus plantarum

@article {pmid41351413,
year = {2025},
author = {Xu, Y and Tao, Y and Pan, H and Wang, Z and Wang, H and Luo, Q},
title = {Microbiome Modulation in Lung Cancer Immunotherapy: Unveiling the Role of Respiratory and Gut Microbiota in the PD-1/PD-L1 Response.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {11},
pages = {41531},
doi = {10.31083/FBL41531},
pmid = {41351413},
issn = {2768-6698},
support = {24ZR1464400//Shanghai Municipal Natural Science Foundation/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Lung Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; *B7-H1 Antigen/antagonists & inhibitors/immunology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; Dysbiosis/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Lung cancer, the leading cause of cancer-related mortality worldwide, poses considerable therapeutic challenges due to the varied responses to programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Emerging highlight the pivotal role of host-microbiome interactions in modulating antitumor immunity and influencing clinical outcomes. This review examines how the respiratory and gut microbiota contribute to the immunosuppressive tumor microenvironment through dysbiosis-induced T-cell exhaustion and regulatory cell activation, while certain commensals facilitate dendritic cell-mediated recruitment of cytotoxic T lymphocytes. Additionally, this review explores the molecular mechanisms by which microbial metabolites, such as short-chain fatty acids, influence myeloid-derived suppressor cells. Therapeutically, microbiota-modulation strategies-such as tailored probiotic formulations and precision fecal microbiota transplantation-offer potential to enhance immunotherapy efficacy. This review provides a foundation for microbiome-guided immunotherapy, advocating for biomarker-driven patient stratification and the use of engineered microbial consortia to counteract therapeutic resistance. These findings pave the way for the integration of microbiome science into next-generation precision oncology.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Lung Neoplasms/therapy/immunology/microbiology
*Immunotherapy/methods
Tumor Microenvironment/immunology
*B7-H1 Antigen/antagonists & inhibitors/immunology
Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology
Immune Checkpoint Inhibitors/therapeutic use
Dysbiosis/immunology
Animals
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid41350095,
year = {2025},
author = {Deleu, S and Sabino, J},
title = {Cutting edge developments and novel targets in IBD: Microbiome in IBD.},
journal = {Best practice & research. Clinical gastroenterology},
volume = {78},
number = {},
pages = {102060},
doi = {10.1016/j.bpg.2025.102060},
pmid = {41350095},
issn = {1532-1916},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Inflammatory Bowel Diseases/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; *Crohn Disease/microbiology/therapy ; *Colitis, Ulcerative/microbiology/therapy ; Synbiotics/administration & dosage ; },
abstract = {Inflammatory bowel disease (IBD), a non-communicable disease encompassing Crohn's disease and ulcerative colitis, is a chronic disorder with increasing prevalence and complex etiology. Emerging evidence highlights the gut microbiome's pivotal role in IBD pathogenesis, driving interest in microbiome-targeted therapeutic strategies. This narrative review explores the latest advancements in microbiome modulation for IBD management, encompassing antibiotics, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Additionally, dietary interventions, physical activity, as well as non-bacterial microbiota components such as fungi, archaea, and bacteriophages are examined for their potential roles in restoring microbial equilibrium and mitigating intestinal inflammation. As research progresses, a multimodal approach integrating microbiota-targeted therapies with lifestyle modifications and conventional pharmacologic treatments may offer a personalized and effective strategy for IBD management.},
}

Humans
*Gastrointestinal Microbiome/drug effects
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Prebiotics/administration & dosage
*Inflammatory Bowel Diseases/therapy/microbiology
Anti-Bacterial Agents/therapeutic use
*Crohn Disease/microbiology/therapy
*Colitis, Ulcerative/microbiology/therapy
Synbiotics/administration & dosage

@article {pmid41297113,
year = {2025},
author = {Lyu, L and Ma, Y and Sun, X and Luo, M and Wang, Z and Fang, L and Li, W and Chen, Y and Liu, S and Jia, X},
title = {Human cord blood mononuclear cells alleviate intestinal inflammation and barrier dysfunction by regulating gut metabolites and Th17/Treg balance.},
journal = {Molecular immunology},
volume = {188},
number = {},
pages = {179-191},
doi = {10.1016/j.molimm.2025.11.004},
pmid = {41297113},
issn = {1872-9142},
mesh = {Animals ; *Th17 Cells/immunology ; *T-Lymphocytes, Regulatory/immunology ; Humans ; Mice, Inbred C57BL ; Male ; Mice ; *Colitis/immunology/therapy/chemically induced/metabolism ; *Fetal Blood/cytology ; *Leukocytes, Mononuclear/immunology/transplantation ; Dextran Sulfate ; *Inflammation/immunology ; *Intestinal Mucosa/metabolism/immunology ; Inflammatory Bowel Diseases/immunology/therapy ; },
abstract = {BACKGROUND: Cord blood mononuclear cells (CB-MNCs) are a potential alternative therapy for inflammatory bowel disease (IBD). Gut metabolites, T helper 17 (Th17) and regulatory T (Treg) cells are crucial for intestinal hemeostasis and recovery. However, the role of CB-MNCs in modulating IBD, gut metabolites and the Th17/Treg balance remains unclear.

METHODS: In this study, dextran sodium sulfate (DSS) was used to induce acute colitis in male C57BL/6 J mice, followed by treatment with CB-MNCs, umbilical cord-derived mesenchymal stem cells (UC-MSCs), or mesalazine. The severity of colitis was assessed daily using the disease activity index (DAI), and feces were collected for metabolomic analysis. Upon sacrifice, the colons, mesenteric lymph nodes (MLNs) and spleens of the mice were preserved for further study.

RESULTS: Our findings demonstrated that compared with UC-MSCs and mesalazine, CB-MNCs treatment had superior efficacy in improving clinical symptoms, tissue repair, promoting intestinal regeneration and integrity. While CB-MNCs were equivalent to UC-MSCs and mesalazine in terms of preserving colon length and anti-inflammatory activity. At the molecular level, CB-MNCs exhibited unique and powerful effects. CB-MNCs were found to significantly increase the abundance of cortisol, corticosterone, and several metabolites with anti-inflammatory and antioxidant activities in the feces of colitis mice. CB-MNCs were also more effective than UC-MSCs and mesalazine at maintaining Th17/Treg balance than UC-MSC and mesalazine in colitis mice.

CONCLUSIONS: The intravenous injection of CB-MNCs can alleviate intestinal inflammation and barrier dysfunction by modulating gut metabolites and the Th17/Treg balance. Therefore, CB-MNCs be a promising treatment for IBD.},
}

Animals
*Th17 Cells/immunology
*T-Lymphocytes, Regulatory/immunology
Humans
Mice, Inbred C57BL
Male
Mice
*Colitis/immunology/therapy/chemically induced/metabolism
*Fetal Blood/cytology
*Leukocytes, Mononuclear/immunology/transplantation
Dextran Sulfate
*Inflammation/immunology
*Intestinal Mucosa/metabolism/immunology
Inflammatory Bowel Diseases/immunology/therapy

@article {pmid41349548,
year = {2025},
author = {Zarour, HM and Trinchieri, G},
title = {Harnessing the Microbiome in Cancer Immunotherapy: Regulation, Prediction, and Therapeutic Targeting.},
journal = {Annual review of immunology},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-immunol-082323-114522},
pmid = {41349548},
issn = {1545-3278},
abstract = {Humans are metaorganisms, composed of both host (human) cells and a roughly equal number of commensal microorganisms-collectively known as the microbiome-residing primarily at epithelial barrier surfaces. This review considers human cancer as a disease of the metaorganism, to which the microbiome contributes by influencing genome stability, tissue organization, inflammation, immunity, tumor initiation and promotion, metastasis formation, and therapeutic response. We summarize evidence demonstrating that machine learning models trained on patients' microbiome features moderately predict clinical response to immunotherapy and the development of immune-related adverse events. We review results from single-arm and randomized clinical trials wherein fecal microbiome transplantation from therapy-responsive patients or healthy donors, when combined with therapy targeting programmed cell death 1 (PD-1), improved outcomes in PD-1-refractory patients or served as an effective first-line intervention. We conclude by highlighting the emerging opportunities and ongoing challenges in leveraging the microbiome to enhance the efficacy and safety of cancer immunotherapy.},
}

@article {pmid41348832,
year = {2025},
author = {Cervantes-Echeverría, M and Jimenez-Rico, MA and Manzo, R and Hernández-Reyna, A and Cornejo-Granados, F and Bikel, S and González, V and Hurtado Ramírez, JM and Sánchez-López, F and Salazar-León, J and Pedraza-Alva, G and Perez-Martinez, L and Ochoa-Leyva, A},
title = {Human-derived fecal virome transplantation (FVT) reshapes the murine gut microbiota and virome, enhancing glucose regulation.},
journal = {PloS one},
volume = {20},
number = {12},
pages = {e0337760},
doi = {10.1371/journal.pone.0337760},
pmid = {41348832},
issn = {1932-6203},
mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Fecal Microbiota Transplantation/methods ; *Virome ; Male ; Diet, High-Fat/adverse effects ; Obesity/therapy/microbiology ; *Feces/virology ; Mice, Inbred C57BL ; *Glucose/metabolism ; Metabolic Syndrome/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; },
abstract = {The gut microbiome, comprising bacteria, viruses, archaea, fungi, and protists, plays a crucial role in regulating host metabolism and health. This study explored the effects of fecal virome transplantation (FVT) from healthy human donors on metabolic syndrome (MetS) in a diet-induced obesity (DIO) mouse model, without diet change. Mice received a single oral dose of human-derived virus-like particles (VLPs) and continued on a high-fat diet (HFD) for 17 weeks. Despite persistent dietary stress, FVT significantly improved glucose tolerance. Longitudinal profiling by virome shotgun metagenomics and bacterial 16S rRNA sequencing revealed marked, durable shifts in both viral and bacterial community composition. Notable bacterial changes included a decrease in Akkermansia muciniphila and Peptococcaceae and increases in Allobaculum and Coprococcus; A. muciniphila positively correlated with glucose levels and negatively correlated with body weight. Together, these results suggests that human-derived virome can durably reshape gut microbial ecology and improve glucose metabolism in mice with obesity, even without dietary modification, offering a novel avenue for developing phage-based therapies. This proof-of-concept study provides foundational observations for using human-derived VLPs for FVT in standard laboratory mouse models, and provides a foundation for elucidating bacteria-phage interactions and their role in host metabolic health.},
}

Animals
*Gastrointestinal Microbiome
Humans
Mice
*Fecal Microbiota Transplantation/methods
*Virome
Male
Diet, High-Fat/adverse effects
Obesity/therapy/microbiology
*Feces/virology
Mice, Inbred C57BL
*Glucose/metabolism
Metabolic Syndrome/therapy/microbiology
RNA, Ribosomal, 16S/genetics
Bacteria/genetics

@article {pmid41346377,
year = {2025},
author = {Ishikawa, D and Zhang, X and Nomura, K and Nagahara, A},
title = {Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Where We Stand and What Is Next.},
journal = {Inflammatory intestinal diseases},
volume = {10},
number = {1},
pages = {371-386},
pmid = {41346377},
issn = {2296-9365},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapeutic strategy for inflammatory bowel disease (IBD). Every step of the FMT process, from donor recruitment and patient selection to pretreatment protocols, administration techniques, and post-FMT interventions, can significantly influence treatment outcomes. These components are interrelated, and even subtle differences in methodology may affect the overall efficacy of FMT for IBD. This review aimed to outline the current clinical experience and findings regarding FMT for IBD during the application process.

SUMMARY: Donor screening has traditionally focused on safety. In recent years, although safety remains essential, increasing attention has been paid to the donor selection efficacy. Particularly, identifying patients who are most likely to benefit from FMT is crucial because timely and appropriate patient selection can prevent delays in effective treatment. Pretreatment strategies and FMT procedures remain hot topics of current research. Approaches, such as antibiotic pretreatment, may enhance microbial engraftment; however, the optimal antibiotic combination remains unclear. Bowel lavage is commonly used to reduce the microbial burden and facilitate donor microbiota colonization, whereas corticosteroid pretreatment has shown conflicting results. There are various routes of administration, and oral capsules are gaining popularity owing to their safety and patient acceptability. Stool preparation factors, including the use of single versus pooled donors, anaerobic processing, and storage form (fresh, frozen, or freeze-dried), can significantly influence microbial viability and clinical outcomes. Repeated FMTs tend to be more effective than single infusions; nonetheless, the optimal frequency remains unclear. Post-FMT interventions, such as dietary modifications and supplementation with prebiotics, such as pectin and alginic acid, are also promising strategies.

KEY MESSAGES: Despite encouraging results, variations in treatment protocols, donor characteristics, and host factors continue to obscure the definitive predictors of FMT success. Further randomized controlled trials and mechanistic studies are required to standardize these procedures and optimize their long-term efficacy.},
}

@article {pmid41346294,
year = {2025},
author = {Salinas-Velarde, ID and Donaciano-Domínguez, JM and Oros-Pantoja, R and Aguirre-Garrido, JF and González-Cervantes, RM and Munguía-Cervantes, JE and López, MG and Bustos-Martínez, J and Soto-Piña, AE},
title = {Narrative Review: Gut Microbiota and Its Impact on α-syn Function in Parkinson's Disease.},
journal = {MicrobiologyOpen},
volume = {14},
number = {6},
pages = {e70173},
doi = {10.1002/mbo3.70173},
pmid = {41346294},
issn = {2045-8827},
support = {//This review was funded by the "Consorcios Proyectos de Colaboración Interinstitucional UAM-IPN -UAEMEX" (grant number 7152/2024ECON) and publication grant 34503067 (UAM-Xochimilco). Additionally, I.D.S.V. received a grant from the Consejo Mexiquense de Ciencia y Tecnología (COMECYT, grant number CAT2024-0080)./ ; },
mesh = {*Gastrointestinal Microbiome/physiology ; *Parkinson Disease/microbiology/therapy/metabolism ; Humans ; *alpha-Synuclein/metabolism ; Fecal Microbiota Transplantation ; Animals ; Bacteria/metabolism/classification ; },
abstract = {Gut microbiota (GM) plays a pivotal role in human health and disease, and its alterations have been implicated in various neurological disorders, including Parkinson's disease (PD). Growing evidence reveals correlations between the abundance of specific bacterial taxa and the severity of motor symptoms and intestinal dysfunction in PD. Moreover, bacterial metabolites have been shown to influence α-synuclein (α-syn) aggregation and neurodegeneration. This narrative review aims to explore the current understanding of the gut-brain axis in PD, specifically the connection between GM and α-syn function in PD experimental models and patients. Several therapeutic strategies aimed at modulating gut microbiota, such as dietary interventions, fecal microbiota transplantation, and targeted bacterial therapies with the goal of alleviating or preventing PD symptoms, are examined. Understanding the mechanisms through which GM influence neurodegeneration, including inflammation, immune modulation, and microbial metabolite production, offers promising avenues for the development of novel therapeutic strategies targeting the microbiome.},
}

*Gastrointestinal Microbiome/physiology
*Parkinson Disease/microbiology/therapy/metabolism
Humans
*alpha-Synuclein/metabolism
Fecal Microbiota Transplantation
Animals
Bacteria/metabolism/classification

@article {pmid41345102,
year = {2025},
author = {Pope, R and Visconti, A and Zhang, X and Louca, P and Baleanu, AF and Lin, Y and Asnicar, F and Bermingham, K and Wong, KE and Michelotti, GA and Wolf, J and Segata, N and Berry, SE and Spector, TD and Leeming, ER and Gibson, R and Menni, C and Falchi, M},
title = {Faecal metabolites as a readout of habitual diet capture dietary interactions with the gut microbiome.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10051},
pmid = {41345102},
issn = {2041-1723},
support = {27/2023//Chronic Disease Research Foundation (CDRF)/ ; },
mesh = {Humans ; *Feces/chemistry/microbiology ; *Gastrointestinal Microbiome/physiology ; *Diet ; Male ; Female ; Metabolome ; Middle Aged ; Metabolomics/methods ; Aged ; Metagenomics ; Adult ; Machine Learning ; },
abstract = {The interplay between diet and gut microbiome composition is complex. Faecal metabolites, the end products of human and microbial metabolism, provide insights into these interactions. Here, we integrate faecal metabolomics, metagenomics, and habitual dietary data from 1810 individuals from the TwinsUK and 837 from the ZOE PREDICT1 cohorts. Using machine learning models, we find that faecal metabolites accurately predict reported intakes of 20 food groups (area under the curve (AUC) > 0.80 for meat, nuts and seeds, wholegrains, tea and coffee, and alcohol) and adherence to seven dietary patterns (AUC from 0.71 for the Plant-based Diet Index to 0.83 for the Dietary Approaches to Stop Hypertension score). Notably, the faecal metabolome is a stronger predictor of atherosclerotic cardiovascular disease risk (AUC = 0.86) than the Dietary Approaches to Stop Hypertension score (AUC = 0.66). We identify 414 associations between 19 food groups and 211 metabolites, that significantly correlate with microbial α-diversity and 217 species. Our findings reveal that faecal metabolites capture mediations between diet and the gut microbiome, advancing our understanding of diet-related disease risk and informing metabolite-based interventions.},
}

Humans
*Feces/chemistry/microbiology
*Gastrointestinal Microbiome/physiology
*Diet
Male
Female
Metabolome
Middle Aged
Metabolomics/methods
Aged
Metagenomics
Adult
Machine Learning

@article {pmid40967279,
year = {2025},
author = {Liao, XN and Huang, LL and Yang, J and Hou, YY and Quan, YX and Bai, YH},
title = {Analysis of the potential mechanism of stem cells in the treatment of diabetic nephropathy based on 16S, metabolome and transcriptome.},
journal = {Genomics},
volume = {117},
number = {6},
pages = {111113},
doi = {10.1016/j.ygeno.2025.111113},
pmid = {40967279},
issn = {1089-8646},
mesh = {*Diabetic Nephropathies/therapy/metabolism/genetics ; Animals ; *Metabolome ; Mice ; *Transcriptome ; RNA, Ribosomal, 16S/genetics ; Male ; *Mesenchymal Stem Cell Transplantation ; *Mesenchymal Stem Cells/metabolism ; Gene Regulatory Networks ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Diabetic nephropathy (DN) has become a major cause of end-stage renal failure. The therapeutic mechanism of mesenchymal stem cells (MSCs) in DN is not fully understood. In this study, we used transcriptome sequencing, 16S rRNA sequencing, and metabolomics sequencing to perform a combined multi-omics analysis to investigate the potential mechanisms of MSCs for DN.

METHODS: First, DN mouse model was established. Kidneys, feces, and blood were collected from 6 control, 6 model, and 6 intervention (MSCs) groups for transcriptome sequencing, 16S RNA sequencing, and metabolome sequencing, respectively. Then, candidate genes between the 3 groups were identified and enriched using transcriptomic analysis. Next, with the help of metabolomics analysis, differential metabolites were screened by OPLS-DA analysis for control and model groups, as well as model and MSCs groups, respectively. Similarly, differential microorganisms and candidate microorganisms were selected by 16S rRNA gene sequencing data. Subsequently, the correlations between candidate genes and candidate metabolites, candidate genes and candidate microorganisms, as well as candidate metabolites and candidate microorganisms were explored by Spearman correlation analysis, respectively. Finally, a microbe-metabolite-gene network was constructed to identify key genes, key metabolites and key microbes, and their expression levels were analyzed.

RESULTS: There were differences in genes, microorganisms, and metabolites among the samples in the control, model, and MSCs groups. Candidate genes enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included adhesion molecules and 2-oxocarboxylic acid metabolism. GDP-mannose biosynthesis and purine ribonucleoside degradation were significantly enriched by different microorganisms. The KEGG pathways mainly enriched for differential metabolites were PPAR signaling pathway, arachidonic acid metabolism, and Rap1 signaling pathway. A microorganisms-metabolite-gene network containing 25 nodes and 53 edges was constructed with interactions including Sorangium-neg-M501T271 and Tmem238l-pos-M373T270, among others. In addition, 10 key genes, 5 key microorganisms and 10 key metabolites were significantly expressed in both the MSCs group and the control group.

CONCLUSION: This study identified 10 key genes, 10 key metabolites and 5 key microorganisms and a correlation network diagram was constructed. It provided a theoretical reference for exploring the molecular mechanisms of MSCs for DN treatment.},
}

*Diabetic Nephropathies/therapy/metabolism/genetics
Animals
*Metabolome
Mice
*Transcriptome
RNA, Ribosomal, 16S/genetics
Male
*Mesenchymal Stem Cell Transplantation
*Mesenchymal Stem Cells/metabolism
Gene Regulatory Networks
Mice, Inbred C57BL

@article {pmid41344956,
year = {2025},
author = {Jia, D and Wang, L},
title = {Opportunities and challenges in applying microbiota to clinical cancer immunotherapy.},
journal = {Trends in microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tim.2025.11.011},
pmid = {41344956},
issn = {1878-4380},
abstract = {Fundamental research has elucidated the indispensable role of gut microbiota in modulating cancer immunotherapy efficacy. Despite promising preclinical findings, few related approaches have reached clinical trials. In this opinion, we provide insights based on current clinical trials using fecal microbiota transplant or specific bacterial strains as adjuvants to enhance immune checkpoint blockade therapy. We also systematically analyze the challenges in trial design, with a focus on donor selection, patient enrollment, implantation procedures, antibiotic use, safety assessment, and endpoint evaluation. Moving forward, we offer a comprehensive '4D' framework (diversity, diffusion, depth, and delicacy) for accelerating the bench-to-bedside translation. It is hoped that this opinion will help researchers and clinicians aiming to harness microbiome-based strategies to improve cancer immunotherapy outcomes.},
}

@article {pmid41344523,
year = {2025},
author = {Yang, Y and Gan, D and Liang, B and Qian, S and Yang, H and Han, C and Wang, Z},
title = {Quyushengxin formula restores the integrity of intestinal barrier by regulating the gut microbiota to ameliorate DSS-induced ulcerative colitis in mice.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120992},
doi = {10.1016/j.jep.2025.120992},
pmid = {41344523},
issn = {1872-7573},
abstract = {The Quyushengxin formula (QYSXF), a clinically validated traditional Chinese medicine (TCM) formula, has been demonstrated to be safe and effective for the treatment of ulcerative colitis (UC), but its mechanism of action in UC treatment is still unclear.

AIMS OF THE STUDY: The aim of this study was to investigate the effects of QYSXF on gut microbiota modulation in DSS-induced colitis mice and to explore its role in regulating intestinal barrier function and inflammation.

MATERIALS AND METHODS: First, the chemical constituents of QYSXF and mouse plasma were identified using high-performance liquid chromatography coupled with mass spectrometry. An active UC mouse model was established by treating the mice with 3% DSS. The efficacy of QYSXF was evaluated by colonoscopy, body weight, disease activity index (DAI), colon length and histological examinations. Faecal microbiota transplantation (FMT) was performed by transferring the faecal from QYSXF-treated donor mice to DSS-induced UC recipient mice. Intestinal barrier integrity and inflammation were assessed through immunofluorescence, ELISA, and western blotting. Additionally, 16S rDNA sequencing was used to elucidate the composition of the QYSXF-regulated microbiota.

RESULTS: QYSXF effectively ameliorated local ulcer surface, reduced weight loss, decreased the DAI, restored colon length, and improved histopathological scores in UC model mice. QYSXF restored the integrity of the mechanical barrier by increasing the expression of tight junction proteins and restored the integrity of the chemical barrier through increased secretion of Mucin 2 (MUC2). FMT with faecal from QYSXF-treated mice ameliorated inflammation and restored both the mechanical barrier and the chemical barrier. Moreover, both QYSXF and FMT reduced the release of proinflammatory cytokines by inhibiting the NF-κB signalling pathway and increasing the release of anti-inflammatory cytokines. 16S rDNA sequencing demonstrated that QYSXF modulated the composition of the gut microbiota by increasing the abundance of beneficial bacterial, specifically Dubosiella and Ligilactobacillus, while concurrently reducing the prevalence of the pathogenic Escherichia-Shigella.

CONCLUSIONS: The mechanism underlying the efficacy of QYSXF involves restoring the composition of the gut microbiota to improve intestinal barrier, reducing the release of proinflammatory cytokines, and ultimately alleviating UC. This research not only confirms the therapeutic potential of QYSXF in UC treatment but also, more importantly, highlights the critical role of gut microbiota regulation in restoring barrier dysfunction and mitigating inflammatory responses involved in the pathogenesis of UC.},
}

@article {pmid41343181,
year = {2025},
author = {Roth, TD and Russo-Savage, L and Bahojb Habibyan, Y and Keenan, CM and Wallace, LE and Nasser, Y and Mawe, GM and Lavoie, B and Sharkey, KA},
title = {Microbial dysbiosis alters serotonin signaling in a post-inflammatory murine model of visceral pain.},
journal = {American journal of physiology. Gastrointestinal and liver physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpgi.00240.2025},
pmid = {41343181},
issn = {1522-1547},
support = {FDN148380//Canadian Institutes of Health Research (CIHR)/ ; DK113800//HHS | National Institutes of Health (NIH)/ ; AT011203//HHS | National Institutes of Health (NIH)/ ; },
abstract = {Serotonin (5-HT) is a multifunctional signaling molecule in the gastrointestinal (GI) tract. 5-HT synthesis is regulated by the gut microbiota. Microbial dysbiosis has been implicated in visceral pain and persistent alterations in gut function that occur following inflammation. Here we tested the hypothesis that alterations in gut microbiota in a post-inflammatory model of visceral pain contribute to dysregulated 5-HT signaling. We used mice treated with dextran sodium sulfate (DSS) 42 days earlier (post-colitis) or untreated mice as donors for fecal microbiota transplants (FMTs) into germ-free mice to explore changes in enterochromaffin (EC) cell populations, expression of 5-HT synthesis, transport, and degradation genes, levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT release. Significant differences were observed in EC cells, Tph1, Slc6a4, and Maoa gene expression, 5-HT and 5-HIAA levels and 5-HT release between germ-free mice and mice receiving an FMT from either control or post-colitis donor mice. We observed no differences in the total number of EC cells, Tph1, or Slc6a4 gene expression of mice after FMT from post-colitis or control mice. However, there was a significant increase in Maoa gene expression in the terminal ileum, an increased 5-HIAA/5-HT ratio in the proximal colon and reduced 5-HT release to mechanical and chemical stimulation in the proximal and distal colon after FMT from post-colitis mice. Collectively, these findings provide additional evidence that the gut microbiota regulates 5-HT signaling. Moreover, they reveal functional changes in EC cell sensitivity in the presence of an altered microbiota after recovery from inflammation.},
}

@article {pmid41342899,
year = {2025},
author = {Wang, LJ and Mo, YK and Cheng, Y},
title = {The role of intratumoral microbiota in the occurrence and progression of tumors and its implications for guiding tumor treatment.},
journal = {Acta microbiologica et immunologica Hungarica},
volume = {},
number = {},
pages = {},
doi = {10.1556/030.2025.02747},
pmid = {41342899},
issn = {1588-2640},
abstract = {In recent years, the presence of microbiota in tumors has been discovered through extensive research, overturning the longstanding belief that "tumors are sterile." Advanced techniques such as 16S rRNA gene sequencing, fecal microbiota transplantation, and the construction of mouse models specific to different tumor types have been utilized to validate the existence of microbiota within various tumors. The intratumoral microbiota significantly influences tumor development by modulating immune responses, mediating inflammatory reactions, and interfering with or enhancing immunotherapy or chemotherapy. For instance, Aspergillus sydowii in lung adenocarcinoma promotes immunosuppression via the Dectin-1/CARD9 pathway, while colibactin-producing Escherichia coli in colorectal cancer facilitates tumor progression through lipid metabolism dysregulation. Moreover, intratumoral microbiota can predict patient prognosis and guide personalized cancer treatment strategies, highlighting their potential as therapeutic targets. This review synthesizes current evidence on the roles of intratumoral microbiota across multiple cancer types and discusses their clinical implications.},
}

@article {pmid41341415,
year = {2025},
author = {Memariani, M and Memariani, H},
title = {Dysbiosis and Therapeutic Modulation of the Gut Microbiota in Multiple Sclerosis: A Narrative Review.},
journal = {Health science reports},
volume = {8},
number = {12},
pages = {e71564},
pmid = {41341415},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: Multiple sclerosis (MS) is a persistent autoimmune disease that affects the central nervous system. The etiology of MS is complex, involving a variety of genetic and environmental factors. Mounting evidence suggests that dysbiosis significantly impacts the progression of MS mainly through its direct effects upon the immune system. Given the vital connection between the gut microbiota and immune health, particularly in the context of autoimmune diseases, this review aims to summarize the existing knowledge regarding alterations in the gut microbiota among MS patients, with a focus on microbiota-based therapeutic approaches.

METHODS: A detailed literature review was carried out to gather contemporary evidence on dysbiosis of the gut microbiota in MS patients. Furthermore, studies dealing with the modification of gut microbiota for therapeutic applications in MS have been included.

RESULTS: A distinct variation in specific bacterial phyla, orders, families, and genera, as well as metabolites, was found in MS patients. Exploring therapeutic options such as antibiotics, probiotics, dietary interventions, fecal microbiota transplantation, phage therapy, and helminth therapy may present valuable opportunities for gut microbiota modification in MS treatment.

CONCLUSION: Altering the gut microbiota in patients with MS may serve as a potentially effective treatment strategy. Nevertheless, future research should prioritize the standardization of these therapies. Finally, it is imperative that researchers concentrate on large-scale studies or trials to scrutinize the practical relevance of these therapeutic options.},
}

@article {pmid41340133,
year = {2025},
author = {Abavisani, M and Sajjadi, SM and Ebadpour, N and Karav, S and Sahebkar, A},
title = {Gut microbiota-cholesterol crosstalk in cardiovascular diseases: mechanisms, metabolites, and therapeutic modulation.},
journal = {Nutrition & metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12986-025-01051-7},
pmid = {41340133},
issn = {1743-7075},
abstract = {Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Genetic factors, and various environmental factors, including nutrition and the composition of the gut microbiota, have been identified as important factors in the initiation of CVD. Among them, the pivotal role of the gut microbiota in modulating cholesterol metabolism and influencing cardiovascular outcomes has recently been highlighted. Extensive research has confirmed that the gut microbiota has direct and indirect regulatory effects on host cholesterol homeostasis. Recent studies have shown that the microbiota can influence blood cholesterol levels and thus the risk of CVD through various pathways, such as the production of certain metabolites such as bile acids (BAs), SCFAs, and TMAO, the activation of nuclear and membrane-bound receptors such as farnesoid X receptor (FXR), the regulation of gene expression involved in lipid metabolism and inflammatory responses, as well as microbial enzymatic pathways. These complex regulatory mechanisms make the gut microbiota a potential therapeutic target in cholesterol-related diseases and CVD. Microbiota-modulating strategies, including the use of probiotics, prebiotics, fecal microbiota transplantation (FMT), and selective antibiotics, have shown beneficial effects in previous studies. In this regard, in this study, we conducted an in-depth investigation of the regulatory effect of intestinal microbiota on cholesterol metabolism and their impact on the development and progression of atherosclerosis and CVD, and described potential therapeutic pathways based on the regulation of intestinal microbiota in CVD.},
}

@article {pmid41339929,
year = {2025},
author = {Yang, Y and Chen, H and Lu, J and Yang, N and Liu, L and Zhang, Q and Tang, M and Li, X and Meng, B and Li, Y and Yu, L and Gao, L and Zhang, H and Wu, T and Zheng, Y and Liu, Y and Shen, Y and Li, J},
title = {Modulating the gut-bladder axis: fecal transplantation protects antibiotic-treated mice from E. coli cystitis via the Ahr/Prg4 pathway.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02267-8},
pmid = {41339929},
issn = {2049-2618},
support = {U24A20643, 82270015, 82400132, 82100017，82302577，82304209, 82370016//National Natural Science Foundation of China/ ; 2023B700,2024C875//Anhui Province Postdoctoral Research Funding Project/ ; 2208085QH236, 2208085MH264, 2308085QH284, 2308085MH243//Anhui Provincial Natural Science Foundation/ ; 202304295107020032, 202304295107020043//Anhui Province Clinical Medical Research Transformation Special Project/ ; 2023AH01008, 2023AH053282//Anhui Province Scientific Research Planning Project/ ; 2023AH010083, 2024AH010114, 2024AH050826//Anhui University Natural Science Research Project/ ; gxbjZD08//Top Talents Academic Funding Key Programs in Universities/ ; 2021xkjT021//Basic and Clinical Cooperative Research Program of Anhui Medical University/ ; MTP2022A015//China Primary Health Care Foundation/ ; },
abstract = {BACKGROUND: Bacterial cystitis, caused by Escherichia coli (E. coli), is a common urinary tract infection that frequently recurs and seriously affects patient health. Although it is known that gut dysbiosis increases susceptibility to recurrent urinary tract infections, its impact on non-complicated bacterial cystitis-the most common and primary form of urinary tract infection-remains uncertain.

RESULTS: This study found that bacterial infection can cause long-term alterations in gut microbiota structure and affect the production of metabolites. Depletion of the gut microbiota worsens the inflammatory response to bacterial infection, disrupts the epithelial barrier of the bladder, and increases E. coli retention in the bladder and bloodstream. Fecal microbiota transplantation was found to significantly alleviate these excessive inflammatory responses. The study also identified that several tryptophan derivatives derived from the gut microbiota were significantly altered during bacterial microbiota depletion and bacterial infection, with indole-3-propionic acid (IPA) exhibiting the most significant alleviating effect on the excessive inflammatory response during infection. Additionally, the study demonstrated that transcriptional activation of the immune-inhibitory protein Prg4 is regulated by the IPA receptor AhR, which is expressed in bladder urothelial cells. Knockout of AhR in bladder urothelial reduced Prg4 expression and overactivated NF-κB signaling, resulting in the loss of the IPA-alleviating effect. This study suggests that the normal gut microbiota can activate AhR in bladder urothelial cells through its metabolite IPA, regulating the transcription of Prg4 and subsequently modulating the inflammatory response to bacterial cystitis caused by E. coli infection.

CONCLUSIONS: These findings provide a theoretical foundation for the clinical diagnosis and treatment of bacterial cystitis by leveraging the gut microbiota and their metabolites as promising therapeutic targets. Video Abstract.},
}

@article {pmid41082373,
year = {2025},
author = {Chen, K and Geng, H and Zheng, Y and Xie, H and Qin, R and Chen, J and Ye, C},
title = {Disruption of Gut Microbiota-Mediated De Novo NAD[+] Synthesis Contributes to the Development of Polycystic Ovary Syndrome.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {45},
pages = {e06497},
doi = {10.1002/advs.202506497},
pmid = {41082373},
issn = {2198-3844},
support = {20240402019GH//Jilin Province Science and Technology Development Plan project/ ; 2024SCZ07//Health Research Talents of Jilin Province/ ; 2024CL04//Spring-Bud Plan Construction Project of China-Japan Union Hospital of Jilin University/ ; },
mesh = {*Polycystic Ovary Syndrome/metabolism/microbiology ; Female ; *Gastrointestinal Microbiome/physiology ; Animals ; Mice ; Humans ; *NAD/biosynthesis/metabolism ; *Dysbiosis/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; },
abstract = {Polycystic ovary syndrome (PCOS) is a severe disorder that compromises female ovarian health and elevates the risk of various diseases, including endometrial cancer. The pathogenesis of PCOS remains poorly understood, which has hindered the development of effective interventions. In this study, it is demonstrated that patients with PCOS exhibit significant gut dysbiosis. FMT from PCOS patients (P-FMT) into mice induced PCOS-associated symptoms and histological alterations. Notably, both PCOS patients and P-FMT mice exhibit distinct metabolic profiles in the gut, suggesting a gut microbiota-mediated metabolic reprogramming. Furthermore, impaired tryptophan metabolism, particularly reduced levels of 3-hydroxyanthranilic acid (3-HAA), is observed in both PCOS patients and P-FMT mice. Administration of 3-HAA to mice alleviated DHEA-induced PCOS. Mechanistically, 3-HAA promoted NAD[+] synthesis via the de novo biosynthesis pathway, thereby inhibiting DHEA-induced ferroptosis by modulating the mitochondrial DNA-cGAS-STING axis. Collectively, these findings reveal the critical role of gut microbiota-mediated NAD[+] synthesis in the pathogenesis of PCOS, underscoring the potential of targeting gut microbiota and NAD[+] homeostasis as a therapeutic strategy for PCOS prevention and management.},
}

*Polycystic Ovary Syndrome/metabolism/microbiology
Female
*Gastrointestinal Microbiome/physiology
Animals
Mice
Humans
*NAD/biosynthesis/metabolism
*Dysbiosis/metabolism
Disease Models, Animal
Fecal Microbiota Transplantation

@article {pmid41338385,
year = {2025},
author = {Zhang, X and Qi, J and Dong, C and Zhang, L and Chen, J and Liu, J and Jiang, T and Song, J},
title = {Intratumoral microbiota in colorectal cancer: roles, therapeutic potential, and challenges.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.11.067},
pmid = {41338385},
issn = {2090-1224},
abstract = {BACKGROUND: Colorectal cancer (CRC) is a multifactorial disease characterized by disruptions in cellular and immune functions, influenced by genetic mutations, environmental factors, and infections. Recent studies have highlighted the intratumoral microbiota as a critical component of the tumor microenvironment (TME), with a significant role in CRC initiation, progression, and therapeutic response. While the gut microbiota's influence on CRC is well-established, the specific contribution of intratumoral microbiota remains inadequately explored. Emerging evidence suggests that intratumoral microbiota may promote cancer progression through inflammatory pathways, metabolic alterations, and resistance to chemotherapy. Conversely, certain microbial communities exhibit tumor-suppressive properties by modulating immune responses and inducing apoptosis in tumor cells.

AIM OF REVIEW: This review aims to highlight the dual role of the intratumoral microbiota in CRC and explore the potential of microbial interventions such as probiotics, phage therapy, and fecal microbiota transplantation (FMT) in enhancing therapeutic outcomes. Furthermore, the review examines the potential of microbiota-targeted therapies to optimize cancer treatment strategies and stresses the need for personalized approaches based on microbial biomarkers.

Intratumoral microbiota, as emerging tumor components, has been identified in various solid tumors. The review emphasizes the mechanisms by which intratumoral microbiota mediate inflammation, metabolic alterations, and immune modulation in CRC. It highlights how certain intratumoral microbiota are associated with resistance or sensitivity to treatments, and how manipulating the microbiota could enhance immunotherapy efficacy. By integrating advancements in multi-omics and clinical research, targeting the intratumoral microbiota represents a promising avenue for improving CRC therapies and overcoming treatment resistance. The clinical application of the intratumoral microbiota has the potential to revolutionize the treatment of CRC, paving the way for novel therapeutic strategies in oncology.},
}

@article {pmid41339918,
year = {2025},
author = {Liu, H and Xiong, X and Zhu, W and Wang, S and Huang, W and Zhu, G and Xu, H and Yang, L},
title = {Gut microbial metabolites in cancer immunomodulation.},
journal = {Molecular cancer},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12943-025-02521-5},
pmid = {41339918},
issn = {1476-4598},
support = {2022YFC3602900//National Key Research and Development Program of China/ ; 82372831//National Natural Science Foundation of China/ ; },
abstract = {Gut microbiota-derived metabolites are emerging as systemic "remote immunoregulators" that shape tumor immunity across tissues. Integrating evidence across short-chain fatty acids, tryptophan derivatives, secondary bile acids, polyamines and other metabolites, we advance a metabolite-immune pathway-cancer framework that links receptor-mediated signaling, epigenetic remodeling and metabolic reprogramming to context-dependent, bidirectional immune effects. Importantly, in addition to the g protein-coupled receptor / aryl hydrocarbon receptor pathway, the selected microbial small molecule metabolites are the true T-cell receptor ligands of unconventional T cells, directly shaping the tissue resident immune and tumor microenvironment, supplementing the receptor signaling and epigenetic programs in our framework. We synthesize how these metabolites recalibrate the tumor immune microenvironment-modulating antigen presentation, T-cell effector fitness and exhaustion, regulatory T-cell activity, and myeloid polarization-and why the same metabolite can either potentiate immune surveillance or entrench immunosuppression depending on ligand-receptor pairing, dose and tissue niche. We compare tumor-type specific patterns (e.g., colorectal, liver, lung, breast and prostate cancers) to highlight common circuits and organ-restricted idiosyncrasies. Methodologically, we outline how single-cell and spatial multi-omics, imaging mass spectrometry and functional biosensors now enable co-registration of metabolite exposure with immune-cell states in human tumors, providing an actionable basis for biomarker discovery. Given ongoing debate about signals attributed to intratumoral microbiota in low-biomass tumor tissues, we foreground quantifiable, spatially mappable and pharmacologically tractable metabolite-receptor pathways, using microbe-associated molecular patterns / translocation as comparators to judge when chemical signals should be prioritized as intervention targets. Finally, we evaluate precision intervention avenues-including fecal microbiota transplantation, rational bacterial consortia, engineered microbes and nanoparticle-enabled metabolite delivery-and propose stratification rules that pair metabolite/receptor signatures with fit-for-purpose delivery. Together, mapping tissue-specific metabolite-immune circuits and embedding them in robust biomarker frameworks may convert microbial metabolites from correlative markers into therapeutic targets and tools, improving the efficacy and durability of cancer immunotherapy.},
}

@article {pmid41338419,
year = {2025},
author = {Wei, MX and Wu, XY and Lin, JW and Huang, JY and Cheng, J and Huang, WF and Xu, GH and Yi, LT},
title = {Astaxanthin alleviates DSS-induced ulcerative colitis in mice associated with Nrf2-mediated ferroptosis independently of gut microbiota modulation.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110212},
doi = {10.1016/j.jnutbio.2025.110212},
pmid = {41338419},
issn = {1873-4847},
abstract = {Astaxanthin, a natural carotenoid predominantly synthesized by marine microorganisms, has shown promise in attenuating inflammatory diseases, yet its role in colitis remains unclear. Here, we evaluated the therapeutic effects of astaxanthin in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Our findings revealed that astaxanthin significantly ameliorated colitis symptoms, notably at the dose of 100 mg/kg, demonstrated by reduced Disease Activity Index (DAI), increased colon length, diminished colon histopathological damage, and enhanced goblet cell population. Mechanistically, astaxanthin decreased proinflammatory cytokines and malondialdehyde (MDA) levels, suppressed Keap1 expression, activated phosphorylated Nuclear factor erythroid 2-related factor 2 (Nrf2), and increased downstream protein expression of HO-1 and GPX4, ultimately inhibiting ferroptosis. Although astaxanthin altered gut microbiota composition, antibiotic treatment and fecal microbiota transplantation confirmed that its anti-colitis effects were independent of microbiota changes. These findings suggest that astaxanthin alleviates colitis associated with Nrf2 pathway mediated ferroptosis, rather than through gut microbiota modulation.},
}

@article {pmid41338112,
year = {2025},
author = {Hu, L and Zhang, Z and Xu, T and Ma, P and Wang, Z and Zhang, L and Chen, J and He, P and Yang, X and Du, G and Lian, F and Li, X and Qiang, G},
title = {Jiangtang Tiaozhi Formula alleviates obesity by enhancing adipose thermogenesis via TGR5-mediated gut-liver-adipose axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157608},
doi = {10.1016/j.phymed.2025.157608},
pmid = {41338112},
issn = {1618-095X},
abstract = {BACKGROUND: Development of safe and effective anti-obesity drugs has emerged as an urgently needed issue. Jiangtang Tiaozhi Formula (JTTZF), a traditional Chinese medicine formulation, has demonstrated potential antidiabetic and hypolipidemic properties. However, the anti-obesity efficacy of JTTZF and its mechanisms remain insufficiently understood.

METHODS: We assessed the pharmacodynamic effects of JTTZF in diet-induced obese (DIO) mice, as well as in HepG2 cells and adipocytes, focusing on body weight and glucose/lipid metabolism in vivo and in vitro, respectively. 16S rDNA sequencing profiling and fecal microbiota transplantation (FMT) were applied to validate the contribution of gut microbiota in anti-obesogenic effects of JTTZF. Untargeted fecal metabolomics was utilized to explore the potential metabolic pathways mediating gut-liver-adipose axis leading to anti-obesity effect of JTTZF via thermogenesis, which were subsequently confirmed by qPCR detection.

RESULTS: JTTZF exhibited a significant effect of anti-obesity and metabolic benefit, including inhibiting weight gain and adiposity, reducing blood glycolipid, ameliorating glucose intolerance and insulin resistance, together with protecting against hepatic steatosis, compared with orlistat. Mechanistically, JTTZF boosted white fat browning and brown fat thermogenesis. More importantly, JTTZF remodeled gut microbiota by enhancing the colonization of beneficial bacteria. Further JTTZF-FMT induced weight loss and metabolic benefits in DIO mice, verifying that gut microbiota played a crucial role in the anti-obesity effect of JTTZF. Additionally, enrichment analysis of differential metabolites revealed that JTTZF obviously upregulated bile acid metabolism pathway, which promoted TGR5-mediated thermogenesis and energy expenditure in adipose tissue.

CONCLUSION: JTTZF exerted significant anti-obesity effect and metabolic benefits via gut-liver-adipose axis, indicating that JTTZF hold a promising potential at the preclinical stage for obesity treatment.},
}

@article {pmid41337940,
year = {2025},
author = {Han, M and Dong, X and Zhao, R and Hu, X and Li, D and Yan, X and Liu, Y and Du, Q and Li, M},
title = {Fecal metabolomics in Crohn's disease reveal N-Acetylglutamine as a Th17/Treg modulator.},
journal = {Molecular immunology},
volume = {189},
number = {},
pages = {82-97},
doi = {10.1016/j.molimm.2025.11.012},
pmid = {41337940},
issn = {1872-9142},
abstract = {The gut microbiota is widely recognized as a key component in the pathogenesis of inflammatory bowel disease (IBD), and one of its primary modes of interaction with the host occurs via metabolites. Studies have confirmed that gut microbiota dysbiosis affects immune maturation, immune homeostasis, host energy metabolism, and the maintenance of mucosal integrity. However, the specific metabolites that influence the differentiation of mucosal CD4[+] T cells remain insufficiently elucidated. This study aimed to identify and validate unknown metabolites capable of affecting the differentiation of CD4[+] T cell subsets by characterizing changes in fecal metabolites between IBD patients and non-IBD controls. Using untargeted metabolomics, we quantitatively detected a total of 1480 metabolites in positive ion mode and 1178 metabolites in negative ion mode. Regression analysis results showed that N-Acetylglutamine was significantly downregulated in IBD patients and was identified as a key differential metabolite. Further in vitro functional experiments confirmed that this metabolite could directly regulate the differentiation balance of CD4[+] T cells, specifically inhibiting the differentiation of pathogenic Th17 (pTh17) cells while promoting the generation of Treg. This study verifies the critical role of the metabolite N-Acetylglutamine in regulating the Treg/pTh17 cell balance, providing a theoretical basis for its potential as a therapeutic target for IBD.},
}

@article {pmid41337660,
year = {2025},
author = {Silva, IB and Puig-Domingo, M},
title = {The impact of thyroid disorders on the gut microbiome: emerging mechanisms and clinical relevance.},
journal = {Archives of endocrinology and metabolism},
volume = {70},
number = {Spe1},
pages = {e250075},
doi = {10.20945/2359-4292-2025-0075},
pmid = {41337660},
issn = {2359-4292},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Thyroid Diseases/microbiology/immunology/metabolism ; Dysbiosis/microbiology/immunology ; Thyroid Gland/metabolism/immunology ; Animals ; Clinical Relevance ; },
abstract = {The thyroid-gut axis represents a dynamic interaction between the intestinal microbiota and thyroid function, with growing evidence linking gut dysbiosis to thyroid diseases. The gut microbiome, comprising over 100 trillion microorganisms, influences immune modulation, iodine metabolism, and thyroid hormone regulation. Short-chain fatty acids, produced by beneficial gut bacteria, support immune homeostasis and thyroid function, while pathogenic bacteria and lipopolysaccharides trigger inflammatory pathways that impair thyroid activity. Alterations in gut microbiota composition have been associated with autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves' disease. Dysbiosis increases intestinal permeability, antigen exposure, and immune activation, exacerbating thyroid autoimmunity. A reduction in short-chain fatty acids-producing bacteria weakens immune tolerance, promoting inflammatory cytokine release and autoantibody production. Recent studies highlight microbial metabolites such as tryptophan derivatives and their role in immune regulation. Gut dysbiosis is also implicated in thyroid nodules and cancer. Decreased butyrate-producing bacteria and increased inflammatory bacterial taxa have been observed in thyroid malignancies. Microbiota influence iodine and selenium bioavailability, essential for thyroid hormone synthesis, and modulate sodium-iodide symporter expression, affecting thyroid cancer response to radioactive iodine therapy. Microbiome-targeted interventions, including probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation, may restore microbial balance, enhance immune regulation, and improve thyroid treatments. This review synthesizes our current understanding of the thyroid-gut axis, indicating that the intestinal microbiota and its metabolites may act directly or indirectly on the thyroid gland, highlighting potential clinical implications and paving the way for therapeutic strategies targeting the intestinal microbiota.},
}

Humans
*Gastrointestinal Microbiome/physiology/immunology
*Thyroid Diseases/microbiology/immunology/metabolism
Dysbiosis/microbiology/immunology
Thyroid Gland/metabolism/immunology
Animals
Clinical Relevance

@article {pmid41335362,
year = {2025},
author = {Jia, Y and Shi, Y and Wang, J and Liu, H and Wang, H and Huang, Y and Liu, Y and Chen, P and Peng, J},
title = {Astragalin attenuates caerulein-induced acute pancreatitis by targeting the NLRP3 signaling pathway and gut microbiota.},
journal = {Bioresources and bioprocessing},
volume = {12},
number = {1},
pages = {139},
pmid = {41335362},
issn = {2197-4365},
support = {82170661//National Natural Science Foundation of China/ ; 2023DK2002//Key Project of Research and Development Plan of Hunan Province/ ; 2025JJ60669//Hunan Provincial Natural Science Foundation of China/ ; 2024M763719//China Postdoctoral Science Foundation/ ; GZC20242045//Postdoctoral Fellowship Program of CPSF/ ; },
abstract = {BACKGROUND: Acute pancreatitis (AP) has caused great concern worldwide due to its serious threat to human health. Astragalin is a bioactive natural flavonoid compound with several pharmacological activities, but it remains unclear about its effect on AP. The objective of this experiment was to explore the mitigating efficacy of astragalin on caerulein-induced AP model and examine the underlying mechanisms.

METHODS: Following the assessment of astragalin's direct effects on pancreatic acinar cells using an in vitro AP model, an in vivo mouse model was established to further validate its efficacy and elucidate the underlying mechanisms. Pancreatic histopathology, amylase, and lipase levels of mice were observed to determine the optimal therapeutic dose of astragalin. The network pharmacology and RNA sequencing technology were used to reveal the possible targets and pathways. Subsequent molecular docking and western blot were conducted to validate the association between astragalin and key target molecules, as well as the NLRP3 signaling pathway. Combined with metagenomics and metabolomics analysis, the astragalin effective gut microbiota-metabolite-gene network was constructed. Moreover, fecal microbiota transplantation experiments were performed to clarify the importance of gut microbiota in astragalin-mediated alleviation of AP.

RESULTS: The results showed that astragalin attenuated caerulein-induced injury in AR42J cells in vitro. Consistent with these findings, in vivo experiments revealed that astragalin treatment significantly improved pancreatic pathological injury, cell apoptosis, and systemic inflammatory response in AP mice, particularly at high doses. The integrated analysis of network pharmacology and transcriptomics revealed that the NLRP3 signaling pathway was a key molecular pathway, which was further validated using western blot. Docking analysis showed that 12 target genes had good docking activity with astragalin. More intriguingly, it was found that astragalin could reverse gut microbiota dysbiosis by restoring microbial diversity, altering bacterial community composition, and modulating key metabolic pathways. Specifically, astragalin-effective correlation networks were constructed with Lachnoclostridium sp. YL32, Roseburia intestinalis, Ruminococcus gnavus, Lachnospiraceae bacterium Choco86, Anaerobutyricum hallii, etc. as the core strains, 22 metabolites, including 5-Methoxytryptophan, D-Serine, L-Tryptophan, L-Methionine, etc. as core metabolites, and NLRP3 pathway-related genes as the main regulatory targets. Furthermore, fecal microbiota transplantation experiments confirmed the involvement of gut microbiota in AP remission.

CONCLUSION: Collectively, these findings identify astragalin as a promising therapeutic agent for AP, targeting both the NLRP3 signaling cascade and gut microbial homeostasis.},
}

@article {pmid41334562,
year = {2025},
author = {Yurtseven, B and Aydemir, E and Ayaz, F},
title = {The Role of Intestinal Microbiota and Immune System Interactions in Autoimmune Diseases.},
journal = {ImmunoTargets and therapy},
volume = {14},
number = {},
pages = {1347-1372},
pmid = {41334562},
issn = {2253-1556},
abstract = {BACKGROUND: The intricate interplay between the intestinal microbiota and the immune system has emerged as a central theme in understanding autoimmune disease pathogenesis. This review comprehensively explores the role of gut microbiota in shaping immune development, establishing immune tolerance, and contributing to both local and systemic immune regulation.

METHODS: This review synthesizes the modulatory effects of microbial metabolites (eg, short-chain fatty acids and indole derivatives) on regulatory T cells (Tregs) and inflammatory pathways. The concept of "dysbiosis" is examined from functional and compositional perspectives, linking microbial imbalances to autoimmune disorders (IBD, MS, RA, and T1D). Microbiota-targeted therapeutic interventions (probiotics, prebiotics, FMT) are also evaluated.

KEY FINDINGS: The synthesis of the literature confirms that microbial metabolites have a direct impact on Treg differentiation and inflammatory pathways. Dysbiosis, through functional and compositional disruptions, is strongly associated with the pathogenesis of various autoimmune disorders, including Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis, and Type 1 Diabetes. Therapeutic interventions such as probiotics, prebiotics, and Fecal Microbiota Transplantation show promising potential in restoring microbial and immune homeostasis.

CONCLUSION: This review highlights the role of the gut-immune axis in autoimmune diseases. Despite current challenges, such as individual variability and determining causality, future directions toward precision microbiota and immune modulation are promising. This study provides a robust foundation for researchers and clinicians seeking to understand and therapeutically target the gut-immune axis.},
}

@article {pmid41334445,
year = {2025},
author = {Jing, M and Jiang, Y},
title = {Microbiome-mediated crosstalk between T2DM and MASLD: a translational review focused on function.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1677175},
pmid = {41334445},
issn = {1664-2392},
mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/complications ; *Gastrointestinal Microbiome/physiology ; Animals ; *Non-alcoholic Fatty Liver Disease/microbiology/metabolism ; *Fatty Liver/microbiology/metabolism ; },
abstract = {Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently co-occur and aggravate one another through shared pathways of insulin resistance, low-grade inflammation and disordered lipid handling. Framing their interaction through the gut-liver-pancreas axis, this review synthesizes recent progress with a function-first emphasis, moving beyond taxonomic lists to the microbial outputs most consistently linked to dual metabolic-hepatic endpoints. We summarize how short-chain fatty acids (SCFAs), bile acids (BAs), lipopolysaccharide (LPS) and other microbe-associated molecular patterns, branched-chain amino-acid (BCAA) catabolites, trimethylamine N-oxide (TMAO) and endogenous ethanol reach the liver via portal inflow or the enterohepatic BA cycle and act on epithelial, immune and endocrine interfaces, including the farnesoid X receptor (FXR), G-protein-coupled BA receptor 1 (TGR5) and fibroblast growth factor 19/15 signaling. Mechanistic routes-barrier dysfunction and endotoxaemia; SCFA signaling with effects on enteroendocrine tone and substrate flux; BA remodeling that resets hepatic and pancreatic set-points; and nitrogen/choline and ethanol pathways that promote lipotoxic injury-offer biologically coherent explanations for parallel trajectories of hyperglycemia and steatosis/inflammation. We appraise therapeutic modulation spanning diet and fermentable substrates, live biotherapeutics/postbiotics, BA-targeting drugs, fecal microbiota transplantation and metabolic/bariatric surgery, and we outline clinically actionable biomarker opportunities using function-based panels (fermentative capacity, BA transformation, inflammatory ligands, nitrogen/methyl flux) integrated with host metabolites and genetics for diagnosis, risk stratification and response prediction. By advocating standardized reporting, careful control of diet/medications and composite metabolic-hepatic endpoints in prospective trials, this review provides a practical framework to accelerate translation from association to targeted prevention and therapy that improves glycemic control and MASLD activity in parallel.},
}

Humans
*Diabetes Mellitus, Type 2/microbiology/metabolism/complications
*Gastrointestinal Microbiome/physiology
Animals
*Non-alcoholic Fatty Liver Disease/microbiology/metabolism
*Fatty Liver/microbiology/metabolism

@article {pmid41332712,
year = {2025},
author = {Romo, R and Ricks, E and Ogden, R and Bonnette, PE and Olson, SC and Pearman, K and Call, GB and Chaston, JM},
title = {Whole-body homogenates restore disrupted microbiota composition in a model insect better than feces or no restoration treatment.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.17.688872},
pmid = {41332712},
issn = {2692-8205},
abstract = {UNLABELLED: Antibiotic treatment can disrupt gut microbiota and pose challenges and opportunities for the establishment or restoration of healthy microbial communities. Using the fruit fly, Drosophila melanogaster , as an experimental model, we evaluated the impact of two types of microbial transplants-fly feces and whole-body fly homogenates-on host microbiota composition, following, or independent of, tetracycline-induced community disruption. Using 16S rRNA sequencing, we compared community beta diversity between treatments. We show that antibiotic treatment significantly altered microbiota composition and community structure relative to untreated controls. Flies inoculated with whole body homogenates of age-matched, antibiotic-free flies had a more similar microbial community composition to the untreated communities than flies exposed to fly feces or to flies that received no restoration treatment. We also found that the presence of Wolbachia was associated with variation in microbiota composition and specific locomotor functions. These findings show that whole-body homogenates are a superior method for microbiota restoration in Drosophila melanogaster and contribute to a growing body of research on microbial community restoration following disturbance.

IMPORTANCE: Gut microbes play a critical role in animal biology, influencing digestion, immunity, development, and behavior. Disruptions to the gut microbiota-whether from antibiotics, disease, or other interventions-can have lasting effects, and restoring these communities remains an important challenge across biological and biomedical research. Model organisms like fruit flies (Drosophila melanogaster) provide a powerful system for testing microbial restoration methods because their gut communities are relatively simple and easy to manipulate. In this study, we compared various strategies for repopulating the microbiota of flies following antibiotic treatment. We found that flies fed whole-body homogenates of untreated flies more closely resembled the microbiota of untreated flies than flies exposed to fly feces or to flies that received no restoration treatment. These findings contribute to broader efforts to understand and develop methods for microbiota recovery following disturbance and suggest applications across animal systems.},
}

@article {pmid41332430,
year = {2025},
author = {Li, L and Zhou, N and Wang, Z and Wang, T and Wang, Y and Qiao, F and Du, ZY and Zhang, ML},
title = {Intestinal microbiota contributes to the heterogeneity of fat deposition by promoting mitochondrial fatty acid β-oxidation.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2593076},
doi = {10.1080/19490976.2025.2593076},
pmid = {41332430},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Fatty Acids/metabolism ; Carnitine/biosynthesis/metabolism ; Oxidation-Reduction ; *Mitochondria/metabolism ; Zebrafish ; Lipid Metabolism ; *Bacteria/classification/genetics/metabolism/isolation & purification ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Male ; Humans ; Feces/microbiology ; },
abstract = {The gut microbiota plays a crucial role in lipid metabolism in both humans and animals. However, the specific contributions of gut microbiota and their associated metabolites to fat deposition, as well as the underlying mechanisms, remain largely unexplored. In this study, we demonstrated that the intestinal microbiota mediated the heterogeneity of mesenteric fat index (MFI), as evidenced by fecal microbiota transplantation (FMT) experiments. Notably, analysis of the 16S rRNA gene amplicon sequencing of 44 samples revealed a significantly higher abundance of Cetobacterium somerae in the Low MFI group, with a positive correlation to reduced MFI. Serum metabolomics analysis confirmed that L-Carnitine emerged as the most differentially abundant metabolite in the Low MFI group and exhibited a strong positive correlation with C. somerae abundance. Metagenomic analysis showed that microbial genes related to L-Carnitine biosynthesis were significantly enriched in the Low MFI group. Further, C. somerae was isolated and cultured, and its subsequent monocolonization in germ-free zebrafish and tilapia demonstrated its lipid-lowering effects by enhancing mitochondrial fatty acid β-oxidation. Whole genome sequencing demonstrated C. somerae could encode the [EC:1.2.1.3] gene, which promotes the production of 4-trimethylammoniobutanoate, a precursor of L-Carnitine, thereby enhancing L-Carnitine biosynthesis by the host and gut microbiota, leading to the reduced fat deposition in Nile tilapia. In conclusion, C. somerae, a core gut microbe with high abundance in aquatic teleost intestines, plays an important role in host lipid metabolism. This study advances our understanding of how core gut microbes shape host phenotypes and provides novel insights into manipulating core gut colonizers to reduce fat deposition.},
}

*Gastrointestinal Microbiome/physiology
Animals
*Fatty Acids/metabolism
Carnitine/biosynthesis/metabolism
Oxidation-Reduction
*Mitochondria/metabolism
Zebrafish
Lipid Metabolism
*Bacteria/classification/genetics/metabolism/isolation & purification
Fecal Microbiota Transplantation
RNA, Ribosomal, 16S/genetics
Male
Humans
Feces/microbiology

@article {pmid41331614,
year = {2025},
author = {Yu, H and Zhang, Y and Yang, D and Luo, H and Zhou, Y},
title = {Advances in capsule-based fecal microbiota transplantation: clinical applications and innovations.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1370},
pmid = {41331614},
issn = {1479-5876},
support = {LTGD23C040008//Zhejiang Provincial Natural Science Foundation of China/ ; LBY23H200006//Natural Science Foundation of Hebei Province/ ; 2023020612//Ningbo Top Medical and Health Research Program/ ; 2023-S013//Ningbo Public Welfare Project/ ; 06-445-1211//Talent Initiation Program of the High-Level University Development Project at Guangzhou Medical University/ ; },
}

@article {pmid40389632,
year = {2025},
author = {Doyle, B and Reynolds, GZM and Dvorak, M and Maghini, DG and Natarajan, A and Bhatt, AS},
title = {Absolute quantification of prokaryotes in the microbiome by 16S rRNA qPCR or ddPCR.},
journal = {Nature protocols},
volume = {20},
number = {12},
pages = {3441-3476},
pmid = {40389632},
issn = {1750-2799},
support = {R01 AI148623/AI/NIAID NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; T32GM007276//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; D43TW010540//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 AI148623/AI/NIAID NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; },
mesh = {*RNA, Ribosomal, 16S/genetics ; Humans ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; *Polymerase Chain Reaction/methods ; *Real-Time Polymerase Chain Reaction/methods ; *Microbiota/genetics ; *Bacteria/genetics ; *Prokaryotic Cells ; },
abstract = {Measurements of prokaryotic absolute abundance can provide important insights into human gut microbiome biology and correct misinterpretations of relative abundance data. Despite the existence of several relatively well-established methods for making these measurements, most microbiome studies do not report absolute abundance. To enable researchers equipped with standard molecular biology capabilities to incorporate absolute quantification into their microbiome studies, we present a detailed, step-by-step protocol for rigorous and reproducible quantification of prokaryotic concentration in stool samples. We include methods for measuring stool sample moisture content, quantifying the concentration of the 16S rRNA prokaryotic marker gene by qPCR or digital droplet PCR (ddPCR) and analyzing the resulting data. We also highlight and provide strategies to overcome common pitfalls of the quantification method, such as 16S rRNA gene contamination. The final output of this approach is 16S rRNA copies per wet or dry gram of stool. In cases where samples have matched metagenomic sequencing information, data can be converted into absolute concentration of prokaryotes and taxon-specific absolute concentrations. To enable researchers to choose the appropriate method for their specific applications, we also compare and contrast our qPCR and ddPCR methods. In 4 days, ~80 samples can be taken from frozen stool to absolute concentration by using qPCR or ddPCR without the need for resequencing. Overall, this protocol provides a sensitive and straightforward way to measure the absolute concentration of prokaryotes in human gut microbiome samples stored with or without preservative.},
}

*RNA, Ribosomal, 16S/genetics
Humans
Feces/microbiology
*Gastrointestinal Microbiome/genetics
*Polymerase Chain Reaction/methods
*Real-Time Polymerase Chain Reaction/methods
*Microbiota/genetics
*Bacteria/genetics
*Prokaryotic Cells

@article {pmid41329233,
year = {2025},
author = {Guarino, M and Di Ciaula, A and Portincasa, P and De Giorgio, R},
title = {Narrative review on microbiota and sepsis: the host's betrayal?.},
journal = {Internal and emergency medicine},
volume = {},
number = {},
pages = {},
pmid = {41329233},
issn = {1970-9366},
abstract = {Sepsis remains a leading cause of morbidity and mortality worldwide. Increasing evidence suggests that the gut microbiota, long considered a "less relevant" to human body health, it plays a crucial role in the pathophysiology of sepsis. Disruption of the host-microbe balance contributes to impaired barrier integrity, microbial translocation, and dysregulated immune responses. This perspective raises the possibility that dysbiosis is not merely a consequence of critical illness, rather an active driver of septic progression. This narrative review explores the relationship between sepsis and gut microbiome. PubMed, Scopus, and EMBASE were searched from inception to September 2025. Recent studies have highlighted the triangular interplay between the intestinal barrier, gut microbiota, and immune system. Altered microbial composition and increased permeability foster systemic inflammation and immune dysfunction. Biomarkers such as diamine oxidase and intestinal fatty acid-binding protein are emerging as promising indicators of gut injury. Experimental therapies (i.e., faecal microbiota transplantation, targeted probiotics, prebiotics, postbiotics, and personalized antibiotic regimens guided by microbial profiling) provide potential to modulate host-microbe interactions. Integration of microbiome analysis with multi-omics and advanced bioinformatics may enable stratification of septic patients by microbial signatures, paving the way for precision medicine approaches. Modulation of gut microbiota represents a novel therapeutic frontier in sepsis. Conceptualizing sepsis as a disease of disrupted host-microbe symbiosis may unravel new diagnostic and therapeutic strategies. Future research should aim at prioritizing high-quality trials, innovative designs, and equitable implementation to target microbiota to improve survival and recovery in patients with sepsis.},
}

@article {pmid41329062,
year = {2025},
author = {Yun, Y and Xu, GQ and Jiang, XJ and Ren, XY and Lu, MF and Chen, JW and Zhang, SX},
title = {Gut Microbiota in Rheumatoid Arthritis: Unraveling Pathogenic Mechanisms and Therapeutic Opportunities.},
journal = {Comprehensive Physiology},
volume = {15},
number = {6},
pages = {e70078},
doi = {10.1002/cph4.70078},
pmid = {41329062},
issn = {2040-4603},
support = {202203021221269//Natural Science Foundation of Shanxi Province/ ; 82001740//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Arthritis, Rheumatoid/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Dysbiosis/immunology ; Antirheumatic Agents/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Rheumatoid arthritis (RA), a chronic autoimmune disorder driven by genetic-environmental interplay, manifests as progressive synovitis and irreversible joint damage. Despite mechanistic advances in disease-modifying antirheumatic drugs (DMARDs) and biologics, upstream mucosal triggers of autoimmunity remain elusive. Mounting evidence implicates gut microbiota dysbiosis as a pivotal environmental factor in RA pathogenesis through multifaceted mechanisms: (1) compromising intestinal barrier integrity, (2) facilitating molecular mimicry via cross-reactive microbial antigens, (3) skewing mucosal immunity toward pro-inflammatory T helper 17 (Th17)/T follicular helper (Tfh) cell responses, and (4) generating bioactive metabolites with dual roles in regulating osteoclastogenesis and synovial inflammation. This review synthesizes recent advances in gut microbiome profiling, mechanistic studies, and preclinical models, elucidating microbial-host crosstalk in autoimmune cascades. Furthermore, we critically evaluate microbiota-directed strategies, including dietary and probiotic modulation, microbiome-informed optimization of conventional DMARDs and biologics, and investigational approaches like fecal microbiota transplantation and Chinese herbal medicine, that may offer promising adjunctive approaches to complement conventional RA management.},
}

Humans
*Arthritis, Rheumatoid/microbiology/immunology/therapy
*Gastrointestinal Microbiome/physiology/immunology
Animals
Dysbiosis/immunology
Antirheumatic Agents/therapeutic use
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid41327482,
year = {2025},
author = {Wu, J and Guo, P and Wang, M and Men, Z and Lin, Z and Wang, J and Zhang, S and Zhou, M and Zhao, J and Liu, H and Ma, X},
title = {Butyrate-producing commensal bacteria confers colon immune defense function via enhancing H4K31 Crotonylation of macrophages.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02234-3},
pmid = {41327482},
issn = {2049-2618},
support = {32302758//National Natural Science Foundation of China/ ; 32402706//National Natural Science Foundation of China/ ; 31829004//National Natural Science Foundation of China/ ; 2022M723422//China Postdoctoral Science Foundation/ ; GZB20230848//Postdoctoral Fellowship Program of CPSF/ ; 2022YFD1300404//National Key Research and Development Program of China/ ; 1041-00109019//2115 Talent Development Program of China Agricultural University/ ; },
abstract = {BACKGROUND: The mechanisms by which microbiota from disease-resistant populations or animals improve intestinal immune defense remain incompletely elucidated. Tibetan pig, a renowned disease-resistant breed, serve as a valuable research subject for the health of humans and economic animals.

RESULTS: In this study, fecal microbiota transplantation from Tibetan piglets into mice conferred enhanced resistance to C. rodentium DBS100. Further microbiota profiling and metabolomics analysis showed this protection may be partly ascribed to C. butyricum SLZX19-05 in recipients' colon. Administration of C. butyricum SLZX19-05 to germ-free mice resulted in the significantly increased lysozyme expression within colonic macrophages, subsequently bolstering the resistance to C. rodentium infection. In mice and piglets, this C. butyricum similarly elevated the lysozyme level in colon and decreased diarrhea incidence. Conversely, lyz1-knockout heightened mice's susceptibility to C. rodentium, highlighting lysozyme's critical role in immune defense. Mechanistically, this study systematically revealed that C. butyricum enhanced lysozyme expression by inhibiting mTORC1-HDAC3/8 pathway, leading to the increased H4K31 Crotonylation (H4K31Cr) and openness of an upstream region of lyz1 promoter via butyrate in macrophages. Additionally, H4K31-mutant mice showed the leukopenia, further validating the significance of H4K31Cr in immune regulation.

CONCLUSIONS: Collectively, mTORC1-HDAC3/8-H4K31Cr pathway is a key mechanism by which butyrate-producing commensal bacteria enhance immune defense in gut. This discovery provides a novel foundation for the screening and application of the next generation of butyrate-producing probiotics. Video Abstract.},
}

@article {pmid41323559,
year = {2025},
author = {Tian, S and Liu, Y and Yang, H and Chen, K and Li, J and Chen, L and Wu, T and Zhang, L},
title = {Multi-Omics Reveal That Gut Microbial Dysbiosis Drives Lipid Metabolic Disturbances and Inflammation in Gestational Hypertension.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {16411-16425},
pmid = {41323559},
issn = {1178-7031},
abstract = {BACKGROUND: Gestational hypertension (GH) is a common complication during pregnancy that poses serious health risks to both mother and fetus. Recent studies have underscored the potential roles of gut microbiota, lipid metabolism, and inflammatory response in GH's development and progression. However, the exact mechanisms behind these interactions are still unclear. Understanding how gut microbial composition impacts lipid metabolism and inflammation could offer valuable insights into GH's pathogenesis and may lead to new prevention and treatment methods.

METHODS: In this study, we conducted ELISA experiments to detect inflammatory cytokines in the serum of GH patients. Additionally, we performed 16S-rDNA sequencing analysis on the feces of GH patients to investigate the characteristics of their intestinal microbial communities; GH mouse model was constructed to assess the impact of intestinal flora on offspring. Furthermore, we utilized non-targeted lipid metabolomics to analyze lipid metabolic characteristics in the feces and blood of GH patients and established connections between the microbiome and lipidome through correlation analysis.

RESULTS: ELISA tests suggested the levels of inflammatory factors in the serum of GH patients increased significantly, including IL-6, IL-8, IL-17, IL-18, and IFN-γ. In comparison to the normal group, the GH group exhibited a marked reduction in microbial richness. LEfSe analysis found 16 distinct bacterial communities between the two groups. Animal models suggested that fecal microbiota transplantation from the GH group's intestinal flora resulted in a significant decrease in the birth weight of the offspring. Furthermore, comparative analysis of fecal and blood metabolic profiles suggested that TG (54:5/FA22:5) may serve as a key metabolite. Correlation analysis demonstrated that f-Oxalobacteraceae exhibited a significant negative correlation with the inflammatory factor IL-17 and TG (54:5/FA22:5) in the blood, while showing a significant positive correlation with g-Oxalobacter and s-formigenes.

CONCLUSION: Our results establish a connection between gut microbiota, lipid metabolism, and the inflammatory response in patients with GH. This understanding may enhance our comprehension of the underlying mechanisms associated with GH.},
}

@article {pmid41322104,
year = {2025},
author = {Khawaja, TW and Zhao, L and Siddiq, R and Ahmad, MU and Burns, CP and Parker, JM and Wakefield, MR and Fang, Y},
title = {Unmasking the microbiome: the hidden role of gut bacteria in the pathogenesis of colorectal cancer and its prevention strategies.},
journal = {Exploration of targeted anti-tumor therapy},
volume = {6},
number = {},
pages = {1002351},
pmid = {41322104},
issn = {2692-3114},
abstract = {Colorectal cancer (CRC) is a significant global health problem, ranking as the third most common cancer and the second leading cause of cancer deaths in the world. The highest incidence of CRC is found in developed regions, thus underlining its characterization as a Western disease. Major risk factors for CRC include an unhealthy diet, lack of physical exercise, and cigarette smoking. The gut microbiota refers to the complex community of microorganisms inhabiting the digestive tract and plays a crucial role in the maintenance of host health and modulation of immune responses. Gut dysbiosis can be caused by poor diet and alcohol consumption, increasing CRC risk. Specific bacteria, such as Fusobacterium nucleatum and Escherichia coli, may have a close relationship with CRC development, while the beneficial bacteria are frequently depleted in CRC patients. This paper will discuss the mechanisms of colorectal carcinogenesis, focusing on the effects of bacterial genotoxins, immune evasion, inflammation, and diet. Additionally, it reviews preventative strategies including short-chain fatty acids (SCFAs), prebiotics, probiotics, synbiotic supplements, and the method of fecal microbiota transplantation (FMT), showing their potential to improve overall gut health and reduce the risk for CRC. Understanding these mechanisms and implementing specific preventative strategies could significantly enhance clinical interventions and reduce the global burden of CRC.},
}

@article {pmid41321823,
year = {2025},
author = {Zheng, Z and Xie, D and Han, Y and Li, G and Wang, S and Zhang, X and Huang, T and Xu, W and Wu, G},
title = {Deciphering the urinary microbiome and urological cancers: from correlation to mechanisms and treatment.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1699308},
pmid = {41321823},
issn = {1664-302X},
abstract = {Given that the sterility of urine and the urinary tract has been questioned by research, urinary microbiome dysbiosis has been recognized as one of the potential cancer-promoting factors. The composition of the urinary microbial community in healthy individuals has a relatively high similarity at the phylum level, with factors like age and gender influencing the expression and distribution. In contrast, the urinary microbiome of patients with urologic cancers shows significant variability and diversity depending on the type of cancer. Most of the early studies focused on the distribution, aggregation, and expression of microbiota in urologic cancers, warranting advanced studies on the causal relationship between microbes and urologic cancers. Bladder and prostate cancer tumorigenesis and progression can be influenced by microbes through chronic inflammatory or immunomodulatory pathways making them cancer models strongly associated with the urinary microbiome. Here, we summarize the expression characteristics of the microbiomes associated with these cancers and analyze the pathophysiological mechanisms and signaling pathways of the microbiome in the tumor promotion or suppression. By examining the role played by the urinary microbiome in the pathogenesis of urologic cancers, we assess the potential of specific microbial groups as biomarkers for diagnosis and surveillance. Additionally, involving the microbiome or using adjunctive participation in tumor therapy is becoming an emerging cancer treatment option. Improving urinary microbial homeostasis in urinary cancers by direct treatment with microbial products, microbial co-immunotherapy, probiotic-assisted therapy, and fecal microbial transplantation may broaden the scope of therapy and enhance the efficacy of conventional medicines.},
}

@article {pmid41321593,
year = {2025},
author = {Zhao, N and Wang, K and Jiang, Y and Huang, R},
title = {Clinical Treatment and Clinical Application Research Progress of Psoriasis and Intestinal Microbiota Dysbiosis.},
journal = {Clinical, cosmetic and investigational dermatology},
volume = {18},
number = {},
pages = {3155-3164},
pmid = {41321593},
issn = {1178-7015},
abstract = {Psoriasis is a prevalent chronic inflammatory dermatosis. Recent evidence indicates a significant association between gut microbiota dysbiosis and its pathogenesis, potentially mediated through immunoinflammatory modulation and skin barrier integrity. This article systematically reviews the mechanisms linking gut microbiota to psoriasis, with emphasis on clinical treatment strategies targeting microbiota modulation-including probiotics, fecal microbiota transplantation (FMT), dietary interventions, and antibiotic therapies. However, current research exhibits notable limitations: most evidence derives from small-scale studies or animal models, lacking validation via large-scale clinical trials; microbiota-targeted interventions are poorly standardized, and the impact of individual variability on therapeutic outcomes remains unclear; the long-term safety of antibiotics and FMT requires further assessment. While summarizing existing advances, this review presents an evaluative overview to highlight research gaps and proposes future directions, such as integrated multi-omics studies, development of standardized therapeutic protocols, and exploration of personalized microbiota-based strategies, to innovate clinical management of psoriasis.},
}

@article {pmid41321404,
year = {2025},
author = {Shalbaf, N and Sadeghi, S and Homaee, S and Saberian, F},
title = {Probiotics, prebiotics, synbiotics, and FMT for glycemic control: A systematic review of clinical efficacy and mechanistic readouts in type 2 diabetes and related dysglycemia.},
journal = {Metabolism open},
volume = {28},
number = {},
pages = {100419},
pmid = {41321404},
issn = {2589-9368},
abstract = {OBJECTIVE: To systematically evaluate the clinical efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on glycemic control in adults with type 2 diabetes (T2D) and related dysglycemia, and to synthesize associated mechanistic changes in microbial metabolites and composition.

METHODS: A systematic review was conducted following PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception through August 2025 for randomized controlled trials (RCTs) in adults with T2D, prediabetes, or metabolic syndrome. Interventions included probiotics, prebiotics, synbiotics, or FMT compared to control. Outcomes were glycemic indices (e.g., HbA1c, HOMA-IR) and mechanistic biomarkers (e.g., SCFAs, bile acids). Risk of bias was assessed using the Cochrane RoB 2 tool. A narrative synthesis was performed.

RESULTS: Thirty studies were included. Multi-strain probiotics, prebiotics, and synbiotics yielded modest but significant improvements in HbA1c (≈-0.2 to -0.4 %), fasting glucose, and HOMA-IR, particularly with durations ≥12 weeks. These benefits were linked to mechanistic shifts, including increased circulating butyrate and ursodeoxycholate, enrichment of SCFA-producing taxa, and reduced endotoxemia. Efficacy was moderated by concomitant medications: metformin use was synergistic, while sulfonylureas attenuated effects. FMT consistently improved clamp-measured insulin sensitivity in insulin-resistant phenotypes, but its effects on HbA1c were less consistent and donor-dependent.

CONCLUSION: Microbiome-targeted interventions, especially multi-strain probiotics and substrate-matched synbiotics, are effective adjuncts for improving glycemic control, with effects mediated through microbial metabolite production. FMT primarily modulates insulin sensitivity. Clinical outcomes are context-dependent, influenced by intervention design, duration, and pharmacomicrobiomic interactions.},
}

@article {pmid41320323,
year = {2025},
author = {Wu, X and Wu, M and Li, H and Yang, Y and Shen, H and Huang, S and Pan, Y and Tao, L and Guo, S and Chen, J and Wu, Y and Zhong, X and Li, S and Liu, B and Zhang, W and Zhu, R and Fan, L and Wang, W},
title = {Intraperitoneal translocation of gut microbiota induces NETosis and promotes endometriosis.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2025-336185},
pmid = {41320323},
issn = {1468-3288},
abstract = {BACKGROUND: Endometriosis is a debilitating gynaecological disorder with an elusive pathogenesis. While gut microbiota dysbiosis has been implicated, the causal role of gut-peritoneum microbial translocation and the specific mechanisms driving disease progression remain elusive. Notably, the role of peritoneal neutrophils and neutrophil extracellular traps (NETs) in the development of endometriosis remains unknown.

OBJECTIVE: This study aims to delineate the pathogenic pathway linking gut microbiota to peritoneal neutrophil activation and the development of endometriosis.

DESIGN: We combined single-cell RNA sequencing of clinical peritoneal fluid immune cells with functional validation in heterologous and homologous mice models. We further adopted microbial source-tracking analysis of patient cohorts and interventional strategies, including faecal microbiota transplantation (FMT) and administration of green fluorescent protein (GFP)-tagged Pseudomonas aeruginosa.

RESULTS: We identified a unique membrane metalloendopeptidase (MME) positive neutrophil subset (Neu_MME) that is expanded in endometriosis and primed for NETs formation (NETosis). These Neu_MME released NETs in response to bacterial lipopolysaccharides (LPS), which directly captured endometrial cells and enhanced their proliferation and migration, driving lesion development. Accordingly, inhibiting NETosis or degrading NETs significantly suppressed endometriosis in mice. Furthermore, FMT from patients with endometriosis to mice disrupted the intestinal barrier, promoting the translocation of gut microbiota, particularly Pseudomonas, into the peritoneal cavity and the lesions. This translocated Pseudomonas was identified as a key driver of LPS-induced NETosis and disease progression.

CONCLUSION: Our findings define a gut-peritoneum axis in endometriosis, where gut-derived Pseudomonas triggers NETosis in peritoneal Neu_MME to promote disease, suggesting that targeting this bacterium or NETosis represents a viable therapeutic strategy.},
}

@article {pmid41318842,
year = {2025},
author = {Malard, F and Holler, E and Peric, Z and Mehra, V and Duarte, R and Sanz, J and Spyridonidis, A and Poiré, X and Morsink, L and Clausen, J and Bazarbachi, A and Nagler, A and Ciceri, F and Ruggeri, A and Mohty, M},
title = {Microbiotherapy and fecal microbiota transplantation in hematology-oncology: a European clinical perspective to navigate the evolving regulatory framework and the emergence of a new therapeutic class.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {41318842},
issn = {1476-5365},
}

@article {pmid41317880,
year = {2025},
author = {Colica, C and Vecchio, I},
title = {Gut microbiota: origin or panacea for all ills? Part 1: Immune and Metabolic Diseases, Nutrition, and Microbiota-Based Interventions.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108213},
doi = {10.1016/j.micpath.2025.108213},
pmid = {41317880},
issn = {1096-1208},
abstract = {Chronic non-communicable diseases (CNCDs), including obesity, type 2 diabetes, allergies, and autoimmune conditions, represent a significant global health burden, exacerbated by the interplay between genetic and environmental factors, such as diet, and gut microbiota. The gut microbiota is a complex and dynamic microbial community that influences host immune and metabolic systems from birth through adulthood. Dysbiosis - an imbalance in gut microbial composition - has been implicated in the development of low-grade inflammation, insulin resistance, and metabolic and immune disorders. This paper reviews the critical role of gut microbiota in CNCDs, emphasizing its interactions with the immune system, including regulatory T cell induction and the Th1/Th2 balance. Furthermore, it explores the influence of birth mode, diet, and xenobiotics on microbiota composition and function. Finally, the study highlights the potential of microbiota-targeted interventions - such as prebiotics, probiotics, synbiotics, and fecal microbiota transplantation - to modulate gut ecology and mitigate disease risk. From literature revision emerges the need for integrative approaches in disease prevention and management, considering microbiota as a key player in health and disease.},
}

@article {pmid41317866,
year = {2025},
author = {Davido, B and Corcione, S},
title = {Re: 'Faecal microbiota transplantation for urinary tract infections' by Gardlik et al.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.11.028},
pmid = {41317866},
issn = {1469-0691},
}

@article {pmid41317323,
year = {2025},
author = {Phelps, CM and Rodriguez J, DM and Meisel, M},
title = {Protocol for preparing murine fecal microbiota transplant and fecal microbiota metabolites for in vivo and in vitro use.},
journal = {STAR protocols},
volume = {6},
number = {4},
pages = {104240},
doi = {10.1016/j.xpro.2025.104240},
pmid = {41317323},
issn = {2666-1667},
abstract = {Accumulating evidence demonstrates that microbiota-derived metabolites can modulate host immune responses and influence complex pathologies. Despite their therapeutic potential, the isolation of fecal microbial metabolites and their scalable ex vivo production remain challenging. Here, we present a protocol for preparing murine fecal microbiota transplant (FMT) and fecal microbiota metabolites for in vivo and in vitro use. We describe steps for collecting and preparing donor feces, isolating fecal microbial metabolites, and producing fecal microbial metabolites ex vivo with a broth expansion culture. For complete details on the use and execution of this protocol, please refer to Phelps et al.[1].},
}

@article {pmid41317234,
year = {2025},
author = {Hetta, HF and Alanazi, FE and Alqifari, SF and Ali, MAS and Albalwi, MA and Albalawi, AA and Ramadan, YN},
title = {The Gut-Brain Axis in Autism: Inflammatory Mechanisms, Molecular Insights, and Emerging Microbiome-Based Therapies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {211},
pmid = {41317234},
issn = {1559-1182},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism/pathology ; Animals ; *Inflammation/microbiology ; Fecal Microbiota Transplantation ; *Autism Spectrum Disorder/therapy/microbiology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; *Autistic Disorder/therapy/microbiology ; },
abstract = {Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial etiology, including genetic, environmental, and microbial influences. Recent studies have highlighted the gut-brain axis as a crucial mediator in ASD pathophysiology, linking alterations in gut microbiota to neurodevelopmental and behavioral abnormalities. Individuals with ASD frequently exhibit dysbiosis, characterized by an imbalance in gut microbial composition, reduced microbial diversity, and increased intestinal permeability. These changes contribute to systemic inflammation, altered neurotransmitter synthesis, and metabolic dysfunctions, ultimately impacting brain function. Emerging therapeutic approaches targeting gut microbiome, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), have shown potential in alleviating both gastrointestinal (GI) and ASD-related symptoms. This review explores the latest evidence on microbiome alterations in ASD, the mechanisms by which gut dysbiosis influences neurodevelopment, and the therapeutic potential of microbiome-based interventions. Understanding these connections may open new avenues for targeted treatments in ASD management.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Brain/metabolism/pathology
Animals
*Inflammation/microbiology
Fecal Microbiota Transplantation
*Autism Spectrum Disorder/therapy/microbiology
Dysbiosis
Probiotics/therapeutic use
*Brain-Gut Axis
*Autistic Disorder/therapy/microbiology

@article {pmid41316345,
year = {2025},
author = {Li, M and Zhang, X and Lu, J and Xiang, J and Wu, J and Zheng, M and Yang, S and He, L and Shao, X},
title = {Isoliquiritigenin ameliorates Parkinson's disease via gut microbiota remodeling: potential mediating role of Parabacteroides distasonis.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1363},
pmid = {41316345},
issn = {1479-5876},
support = {2024ZF031//Zhejiang Traditional Chinese Medicine Administration/ ; 2024ZF165//Zhejiang Traditional Chinese Medicine Administration/ ; 2023RC287//Medical Science and Technology Project of Zhejiang Province/ ; 2023KY345//Medical Science and Technology Project of Zhejiang Province/ ; 2022KY001//Shaoxing Bureau of Science and Technology/ ; 2023SKY015//Shaoxing Bureau of Science and Technology/ ; 2023A14011//Shaoxing Bureau of Science and Technology/ ; },
mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Chalcones/pharmacology/therapeutic use ; *Parkinson Disease/drug therapy/microbiology ; Fecal Microbiota Transplantation ; *Bacteroidetes/drug effects/physiology ; Male ; Mice, Inbred C57BL ; Dopaminergic Neurons/drug effects/pathology/metabolism ; Mice ; Neuroprotective Agents/pharmacology/therapeutic use ; Behavior, Animal/drug effects ; },
abstract = {BACKGROUND: Increasing evidence implicates the gut microbiota in the pathogenesis of Parkinson's disease (PD). Microbiota-targeted interventions may be a promising therapeutic approach. Isoliquiritigenin (ISL), a natural flavonoid and primary pharmacological constituent of licorice (Glycyrrhiza), has neuroprotective effects. Whether this neuroprotection involves modulation of the gut microbiota is unclear.

PURPOSE: The study assessed whether ISL mediates neuroprotective in PD by modulating the gut microbiota, and investigated the functional involvement of Parabacteroides distasonis (P. distasonis) in this process.

METHODS: Mice with chemically-induced PD were first treated with ISL via oral gavage to assess its therapeutic effects. To investigate the microbiota-mediated mechanisms, fecal microbiota transplantation (FMT) from ISL-treated donors and direct gavage of live or heat-killed P. distasonis were performed in separate cohorts. Behavioral performance, dopaminergic neuron integrity, intestinal barrier function, neuroinflammation, gut microbiota composition, and serum metabolomic profiles were systematically evaluated.

RESULTS: ISL and FMT significantly improved motor deficits and protected dopaminergic neurons in the substantia nigra. ISL treatment compositionally reshaped the gut microbiota by suppressing pro-inflammatory genera and enriching beneficial bacteria, such as Parabacteroides. Oral administration of live P. distasonis fully reproduced the neuroprotective effects of ISL, including improved motor function, reduced neuroinflammation, restoration of blood-brain barrier integrity, and attenuation of intestinal mucosal damage. Heat-killed P. distasonis had no significant effects. Metabolomic analysis revealed that ISL and live P. distasonis jointly regulate neuroprotective pathways and metabolites related to the gut-brain axis.

CONCLUSION: ISL alleviates PD-related pathology partly through gut microbiota remodeling, with P. distasonis as a potential mediator.},
}

*Gastrointestinal Microbiome/drug effects
Animals
*Chalcones/pharmacology/therapeutic use
*Parkinson Disease/drug therapy/microbiology
Fecal Microbiota Transplantation
*Bacteroidetes/drug effects/physiology
Male
Mice, Inbred C57BL
Dopaminergic Neurons/drug effects/pathology/metabolism
Mice
Neuroprotective Agents/pharmacology/therapeutic use
Behavior, Animal/drug effects

@article {pmid41316344,
year = {2025},
author = {Ren, Y and Liang, J and Xie, J and Hu, W and Lai, M and Li, X and Zhang, J and Zheng, Y and Wu, Q and Zhou, H and Yin, J},
title = {Sodium oligomannate modulates the gut-brain axis to alleviate post-stroke cognitive impairment by restoring butyrate metabolism.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02257-w},
pmid = {41316344},
issn = {2049-2618},
support = {82171317//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Post-stroke cognitive impairment (PSCI) affects up to half of stroke survivors, severely impacting their quality of life. Despite its prevalence, the pathogenesis of PSCI remains poorly understood, and no specific pharmacological treatments are currently available.

RESULTS: In PSCI patients, fecal butyrate levels were significantly reduced and correlated with cognitive scores. A machine learning model incorporating butyrate levels, butyrate-producing bacteria, and clinical factors (education, smoking, body mass index [BMI], hemoglobin) demonstrates strong predictive performance (area under the curve [AUC]: 0.793 internal, 0.795 external validation). In a transient middle cerebral artery occlusion (tMCAO) mouse model, both sexes displayed sustained gut microbiota dysbiosis featuring decreased butyrate-producing bacteria and fecal butyrate concentrations, concomitant with hippocampal neuronal loss and microglial activation. Sodium oligomannate (GV-971) treatment ameliorated cognitive impairment in a sex-independent manner and restored butyrate-producing gut bacteria. Metagenomic analysis revealed that GV-971 enhanced butyrate production by promoting D-glucuronate degradation and upregulating butyrate synthesis pathway abundance. The elevated butyrate promoted acetylation of histone H3 at lysines 9 and 14 (Ac-H3K9/K14) in colonic and hippocampal neurons, stimulating neurogenesis, while concurrently reducing gut-derived lipopolysaccharide (LPS) and microglial inflammation. Antibiotic treatment and fecal microbiota transplantation established the essential role of butyrate-producing microbiota in mediating GV-971's effects. In vitro, butyrate supplementation significantly inhibited HDAC3 enzymatic activity in HT22 cells and alleviated LPS-induced inflammatory responses in BV2 microglia.

CONCLUSIONS: Intestinal butyrate levels are significantly associated with PSCI. GV-971 mitigates post-stroke cognitive decline by modulating the gut microbiota to increase butyrate production, highlighting its potential as a therapeutic agent for PSCI.},
}

@article {pmid41313610,
year = {2025},
author = {Butcher, J and Gosse, JT and Gobin, J and Ravel-Chapuis, A and Jasmin, BJ and Stintzi, A},
title = {Dystrophic Skeletal Muscle Phenotypes Can Be Horizontally Transferred via Fecal Microbiome Transplantations.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {23},
pages = {e71281},
pmid = {41313610},
issn = {1530-6860},
support = {OGI-149//Genome Canada (GC)/ ; Project 13440//MDECEC | Ontario Ministry of Research and Innovation (MRI)/ ; //Defeat Duchenne Canada (Vaincre Duchenne Canada)/ ; },
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; Mice, Inbred mdx ; *Muscle, Skeletal/pathology/microbiology/metabolism ; *Muscular Dystrophy, Duchenne/therapy/microbiology/pathology ; Mice, Inbred C57BL ; Phenotype ; *Muscular Dystrophy, Animal/microbiology/therapy ; *Gastrointestinal Microbiome ; Male ; },
abstract = {Duchenne muscular dystrophy (DMD) has no cure and accounts for > 80% of muscular dystrophy cases around the world. DMD patients experience severe muscle degeneration that continues until death and also suffer from gastrointestinal complications that undoubtedly impact their microbiotas. It is unclear whether dystrophic microbiotas simply reflect the disease or whether microbes are directly involved in muscle phenotypes. Here, we sought to determine the microbiota's causal role in promoting dystrophic muscles by performing intra/inter-genotype fecal microbiota transplantations (FMT) between wildtype and mdx mice; assessing FMT's impact on muscles and microbiotas over 9 weeks. Transplanting mdx microbiotas into wildtype mice induced an mdx-like muscle phenotype while the inverse improved muscle features. We identified several taxa differentially abundant between wildtype mice receiving either wildtype or mdx FMT, highlighting their potential role in muscle health. Our results highlight the active role microbes have in impacting muscle health through both beneficial and detrimental mechanisms. Accordingly, microbes represent unexploited therapeutic targets for improving health outcomes in muscular dystrophies.},
}

Animals
*Fecal Microbiota Transplantation/methods
Mice
Mice, Inbred mdx
*Muscle, Skeletal/pathology/microbiology/metabolism
*Muscular Dystrophy, Duchenne/therapy/microbiology/pathology
Mice, Inbred C57BL
Phenotype
*Muscular Dystrophy, Animal/microbiology/therapy
*Gastrointestinal Microbiome
Male

@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.},
}