@article {pmid41109696,
year = {2025},
author = {Bunchorntavakul, C and Reddy, KR},
title = {Current Status and Future Directions in the Pharmacologic Management of Cirrhosis.},
journal = {Clinics in liver disease},
volume = {29},
number = {4},
pages = {657-672},
doi = {10.1016/j.cld.2025.06.003},
pmid = {41109696},
issn = {1557-8224},
mesh = {Humans ; *Liver Cirrhosis/drug therapy/complications ; Adrenergic beta-Antagonists/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Anticoagulants/therapeutic use ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Fecal Microbiota Transplantation ; Albumins/therapeutic use ; Rifaximin ; },
abstract = {In recent years, the necessity for pharmacologic treatments to mitigate the risk of hepatic decompensation has been highlighted, with non-selective beta-blockers identified as the most effective option. However, a significant therapeutic gap persists, and additional or alternative treatments have been proposed, including statins, rifaximin, albumin, anticoagulants, angiotensin receptor blockers, granulocyte-colony stimulating factor, and fecal microbial transplant. According to the data from limited clinical trials, these pharmacotherapies offer promising possibilities; nonetheless, additional investigations, particularly randomized controlled trials, are required, in some instances, prior to their incorporation into routine clinical practice.},
}

Humans
*Liver Cirrhosis/drug therapy/complications
Adrenergic beta-Antagonists/therapeutic use
Angiotensin Receptor Antagonists/therapeutic use
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Anticoagulants/therapeutic use
Granulocyte Colony-Stimulating Factor/therapeutic use
Fecal Microbiota Transplantation
Albumins/therapeutic use
Rifaximin

@article {pmid41109693,
year = {2025},
author = {Wagh, RS and Shasthry, SM and Sarin, SK},
title = {New Approaches to Alcohol-Associated Hepatitis.},
journal = {Clinics in liver disease},
volume = {29},
number = {4},
pages = {595-626},
doi = {10.1016/j.cld.2025.06.012},
pmid = {41109693},
issn = {1557-8224},
mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Liver Transplantation ; Fecal Microbiota Transplantation ; Plasma Exchange ; Granulocyte Colony-Stimulating Factor/therapeutic use ; },
abstract = {Severe alcohol-associated hepatitis (SAH) remains a difficult-to-treat severe liver ailment with limited therapeutic options and high mortality. The article reviews new data to help identify the steroid non-responders at the baseline to reduce the risk of infections and increased mortality. New information on the use of growth factors, such as granulocyte-colony stimulating factor, plasma exchange, and fecal microbiota transplantation, has been provided to choose as a monotherapy or with steroids for SAH. Early selection for liver transplantation after careful ethical considerations and risks of recidivism post-transplant can help improve survival upto 70% to 80%.},
}

Humans
*Hepatitis, Alcoholic/therapy
Liver Transplantation
Fecal Microbiota Transplantation
Plasma Exchange
Granulocyte Colony-Stimulating Factor/therapeutic use

@article {pmid41109415,
year = {2025},
author = {Alasbly, G and Alotaishan, S and Algindan, Y and Khattab, R},
title = {Risk Factors for Nosocomial Clostridioides Difficile Infection-Induced Diarrhea in Patients Receiving Enteral Feeding: A Scoping Review.},
journal = {The Journal of hospital infection},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhin.2025.10.005},
pmid = {41109415},
issn = {1532-2939},
abstract = {BACKGROUND: Nosocomial Clostridioides difficile infection (CDI)-induced diarrhea is a major healthcare-associated infection, particularly in critically ill patients. Antibiotic use and disruptions in gut microbiota are known risk factors, and the role of enteral feeding (EF) requires further exploration.

AIM: To examine risk factors for nosocomial CDI-induced diarrhea in hospitalized patients receiving enteral feeding and assess the impact of EF-related factors on CDI outcomes.

METHODS: This scoping review synthesized evidence from recent studies evaluating CDI risk in hospitalized patients on EF, focusing on antibiotic exposure, hospitalization duration, EF type, and gut microbiota alterations.

FINDINGS: Key risk factors identified include prolonged hospitalization, antibiotic use, and feeding tube placement, all of which may facilitate C. difficile colonization. Altered gut microbiota, characterized by reduced bacterial diversity, was associated with prolonged EF and lack of fiber in formulas. Fiber-enriched and polymeric formulas may support microbial balance, while the effects of probiotics on CDI prevention were inconsistent. Management strategies emphasized include antibiotic stewardship, infection control, and optimized nutrition. Fecal microbiota transplantation and bezlotoxumab show promise in reducing recurrence. However, evidence remains limited on whether specific EF modalities (e.g., continuous vs. intermittent feeding, polymeric vs. elemental formulas) directly affect CDI risk.

CONCLUSION: EF may contribute to CDI risk through its impact on gut microbiota and related factors. While certain EF strategies show potential benefits, further research is needed to determine their role in CDI prevention and to develop evidence-based nutritional guidelines for at-risk patients.},
}

@article {pmid41108334,
year = {2025},
author = {Chang, A and Oh, J and Shin, A and Oser, M and Manitius, N and Ghaffari, A and Limketkai, BN},
title = {Similar Symptoms, Distinct Syndromes: Multi-modal Approach to the Patient with an IBD-IBS Overlap.},
journal = {Digestive diseases and sciences},
volume = {},
number = {},
pages = {},
pmid = {41108334},
issn = {1573-2568},
abstract = {Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are distinct gastrointestinal conditions, but they frequently share overlapping clinical symptoms such as abdominal pain, bloating, and altered bowel habits. IBD is defined by the presence of chronic immune-mediated inflammation, and IBS is characterized by gastrointestinal symptoms in the absence of endoscopic and histologic inflammation. When patients with IBD continue to experience IBS-like symptoms despite remission of inflammation, this phenomenon is commonly referred to as IBD-IBS overlap. These patients pose diagnostic and therapeutic challenges, as symptom persistence may reflect lingering immune activation, disrupted barrier function, visceral hypersensitivity, gut-brain axis dysfunction, or microbiome alterations. This review synthesizes emerging evidence on the shared mechanisms underlying IBD and IBS and outlines a multimodal treatment approach that includes pharmacologic management, dietary interventions, mind-body therapies, and microbiome-directed strategies such as probiotics and fecal microbiota transplantation.},
}

@article {pmid41107170,
year = {2025},
author = {Taylor, NA and Sivam, S and van Dorst, J and Coffey, MJ and Visser, S and Haber, P and Volovets, A and Ooi, CY},
title = {Stool and symptom testing in ColoREctal Evaluation for Neoplasia in Cystic Fibrosis (SCREEN-CF).},
journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcf.2025.09.008},
pmid = {41107170},
issn = {1873-5010},
abstract = {BACKGROUND: People with cystic fibrosis (pwCF) have increased colorectal cancer (CRC) risk. Colonoscopy is recommended, yet CF comorbidities increase complexity and risk.

METHODS: We conducted a prospective, observational study of pwCF meeting colonoscopy screening guidelines at an Australian centre (2019 - 2023). Immunochemical faecal occult blood test (iFOBT), faecal calprotectin (FC), and faecal tumour pyruvate kinase isoenzyme type M2 (TuM2-PK) were evaluated for detecting adenomatous polyps and malignant ileocolonic lesions in pwCF. Stools were collected within 3 months of colonoscopy. Diagnostic performance and optimal cut-offs were calculated.

RESULTS: Among 49 participants [mean (SD) age 47.8 (8.2) years; 53 % female], 12 (24.5 %) were post-solid organ transplant, 10 (20.4 %) had > 3 months of triple modulator therapy at stool testing, 12 (24.5 %) had adenomatous polyps and 2 (4 %) had ileocolonic malignancy. Malignancies were in non-transplanted individuals, in the terminal ileum (age 43) and hepatic flexure/ascending colon (age 48). Higher BMI (>23.5 kg/m²) was associated with abnormal colonoscopy (p = 0.03). iFOBT, FC and TuM2PK demonstrated excellent predictive performance for malignancy (AUC 0.93, 1.00, 0.83; all p < 0.05). Only FC had acceptable predictive performance for pre-malignant lesions (AUC 0.73; p = 0.008). For adenomatous polyps, FC ≤100 µg/g achieved a sensitivity of 91.7 % and an NPV of 95.5 %. For ileocolonic malignancy, FC ≥1000 µg/g showed 100 % sensitivity and specificity (p = 0.0009).

CONCLUSION: CRC screening in pwCF is critical given the high prevalence of neoplasia. Alternative non-invasive screening may support risk stratification among individuals with comorbidities, or reluctance, though performance could be influenced by CFTR modulator therapy.},
}

@article {pmid41106539,
year = {2025},
author = {Wang, R and Tang, D and Wu, L and Ou, L and Ding, L and Jiang, J and Wu, Y},
title = {Bielong Ruangan decoction inhibits tumor growth and improves immune response in a hepatocellular carcinoma mouse model through gut microbiota.},
journal = {The international journal of biochemistry & cell biology},
volume = {},
number = {},
pages = {106873},
doi = {10.1016/j.biocel.2025.106873},
pmid = {41106539},
issn = {1878-5875},
abstract = {Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in Mucispirillum_sp. and Helicobacter_typhlonius post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between Mucispirillum and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.},
}

@article {pmid41106199,
year = {2025},
author = {Yu, Z and Wu, J and Han, J and Wang, L and Lu, R and Chen, J and Wang, K and Shi, Z},
title = {Triclosan induced obesity via gut microbiota dysbiosis and butyrate reduction.},
journal = {Ecotoxicology and environmental safety},
volume = {305},
number = {},
pages = {119227},
doi = {10.1016/j.ecoenv.2025.119227},
pmid = {41106199},
issn = {1090-2414},
abstract = {Triclosan (TCS) can influence energy metabolism and is a potential obesogen. However, its underlying mechanisms remain largely unknown. This study investigated how low-dose TCS exposure (0.5 mg/kg/day) disrupts energy metabolism in Sprague-Dawley rats. TCS increased body weight, visceral fat, liver lipid accumulation, and serum triglyceride levels. It also promoted hyperphagia by altering hypothalamic appetite regulation, activating orexigenic neuropeptide Y neurons and suppressing anorexigenic pro-opiomelanocortin neurons. Furthermore, TCS may reduce brown adipose tissue thermogenesis, as indicated by decreased mitochondrial uncoupling protein 1 and tyrosine hydroxylase. These metabolic effects were blocked by subdiaphragmatic vagotomy, confirming gut-brain neural circuit involvement. Mechanistically, TCS reduced gut microbial diversity and butyrate levels. Crucially, both fecal microbiota transplantation from control rats and butyrate supplementation reversed TCS-induced metabolic dysregulation. These findings reveal that TCS-induced gut dysbiosis and butyrate reduction as key drivers of metabolic disturbances and offer insights into the role of environmental chemicals in obesity and potential therapeutic strategies targeting the gut microbiota and butyrate.},
}

@article {pmid41105383,
year = {2025},
author = {Carlsen, A and Steinsbø, Ø and Kvaløy, JT and Aabakken, L and Bolstad, N and Warren, DJ and Karlsen, L and Lundin, KEA and Omdal, R and Grimstad, T},
title = {Optimizing serum adalimumab levels in maintenance therapy via proactive therapeutic drug monitoring improves markers of disease activity in Crohn's disease.},
journal = {Scandinavian journal of gastroenterology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/00365521.2025.2573725},
pmid = {41105383},
issn = {1502-7708},
abstract = {OBJECTS: The benefit of a proactive therapeutic drug monitoring (TDM) strategy in patients with inflammatory bowel disease receiving biological therapy remains disputed. We aimed to evaluate whether optimizing serum adalimumab levels (s-ADL), guided by proactive TDM, is associated with improved markers of disease activity in patients with Crohn's disease.

MATERIALS AND METHODS: In this longitudinal cross-sectional study, 72 patients receiving adalimumab maintenance therapy from our outpatient clinic, were included. Patients underwent five study visits at 3-month intervals over one year. Disease activity was assesed using the Harvey-Bradshaw Index, plasma C-reactive protein (CRP), and fecal calprotectin. s-ADL levels were measured at each visit, and dosing was adjusted to maintain a therapeutic target range of 5.0-12.0 mg/L.

RESULTS: At baseline, subtherapeutic s-ADL levels were associated with higher CRP levels (p = 0.03), and in these patients' drug levels increased significantly over the study (p = 0.001), whereas CRP levels decreased (p = 0.03). Longitudinal analysis demonstrated that higher s-ADL levels (≥5.0 mg/L) were associated with lower CRP levels (p = 0.008) and lower HBI scores (p = 0.03). Additionally, lower CRP- and fecal calprotectin levels at any visit were associated with higher s-ADL levels at the preceding visit (p = 0.04 for both). Lower CRP levels were also associated with higher s-ADL levels using 7.0 mg/L as the therapeutic threshold in longitudinal analyses (p = 0.003).

CONCLUSION: Proactive TDM-guided optimization of s-ADL levels in Crohn's disease patients on adalimumab maintenance therapy was associated with the modest but significant improvements in markers of disease activity over one year of follow-up.},
}

@article {pmid41104042,
year = {2025},
author = {Yassin, LK and Skrabulyte-Barbulescu, J and Alshamsi, SH and Saeed, S and Alkuwaiti, SH and Almazrouei, S and Alnuaimi, A and BaniYas, S and Aldhaheri, D and Alderei, M and Shehab, S and Hamad, MIK},
title = {The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1667448},
pmid = {41104042},
issn = {1663-4365},
abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.},
}

@article {pmid41103946,
year = {2025},
author = {Zhou, L and Li, B and Ren, J and Wang, S and Wang, J},
title = {Microbiome-mediated regulation of chemoradiotherapy response.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1659467},
pmid = {41103946},
issn = {2234-943X},
abstract = {The gut microbiota critically influences patient responses to chemoradiotherapy through bidirectional interactions with host physiology, modulating both therapeutic efficacy and toxicity. Radiotherapy and chemotherapy disrupt microbial homeostasis, exacerbating intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance treatment response via metabolic reprogramming, DNA repair regulation, and immune activation. Key mechanisms include microbiota-mediated TLR/NF-κB signaling, SCFA-dependent epigenetic modifications, and microbial enhancement of immune checkpoint inhibitors. Clinical interventions such as probiotics, fecal microbiota transplantation, and targeted antibiotics demonstrate potential to mitigate toxicity and overcome resistance. This review summarizes emerging evidence on how microbial dysbiosis induced by radiotherapy and chemotherapy exacerbates intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance chemoradiotherapy response via metabolic reprogramming, DNA repair modulation, and immune activation. These findings underscore the gut microbiota as a critical determinant of chemoradiotherapy precision, offering actionable targets for microbiome-guided therapeutic optimization.},
}

@article {pmid41102296,
year = {2025},
author = {Udomkarnjananun, S and Chuaypen, N and Metta, K and Dissayabutra, T and Sodsai, P and Kittiskulnam, P and Tangkijvanich, P},
title = {Dietary composition modulate gut microbiota and related biomarkers in patients with chronic kidney disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {36274},
pmid = {41102296},
issn = {2045-2322},
support = {PMU-B, grant number B36G660010//the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation (PMU-B, grant number B36G660010)/ ; },
mesh = {Humans ; *Renal Insufficiency, Chronic/microbiology/blood ; *Gastrointestinal Microbiome ; Male ; Female ; *Biomarkers/blood ; Middle Aged ; Methylamines/blood ; Cross-Sectional Studies ; Aged ; Cytokines/blood ; Feces/microbiology ; *Diet ; Dietary Fiber ; Adult ; RNA, Ribosomal, 16S/genetics ; },
abstract = {Emerging evidence indicates gut microbiota is essential to chronic kidney disease (CKD) progression. This study investigated the association between gut microbiota profiles, plasma trimethylamine-N-oxide (TMAO), and circulating inflammatory markers in CKD patients according to dietary patterns, particularly low-protein, high-fiber (LP-HF) versus high-protein, low-fiber (HP-LF) diet. In this cross-sectional study, patients with non-dialysis CKD and healthy subjects were enrolled. Dietary patterns among participants were assessed using three-day diet records with detailed nutrient analysis. The 16 S ribosomal RNA sequencing was conducted to examine fecal gut microbiota composition. Plasma samples were analyzed for TMAO concentration and cytokine levels. A total of 135 CKD patients were recruited. A distinct shift in gut microbiota composition in CKD patients was observed compared to 19 healthy controls, particularly a significant reduction of short-chain fatty acid (SCFA)-producing bacteria. TMAO and several cytokine levels were significantly elevated in CKD patients compared to healthy subjects. Within CKD, patients with LP-HF diet displayed a greater abundance of SCFA-producing bacteria, such as the Lachnospiraceae NK4A136 group and Eubacterium ruminantium group, than those with the HP-LF diet. The HP-LF subgroup showed enriched proteolytic bacterial genera such as Klebsiella. The HP-LF subgroup also exhibited significantly higher plasma levels of TMAO, interleukin (IL)-18, and monocyte chemoattractant protein-1 (MCP-1). CKD patients displayed marked alterations in gut bacterial composition compared to healthy controls. Our results also highlighted the potential advantages of adopting a high fiber-rich and low-protein diet intake in reducing gut dysbiosis in CKD patients.},
}

Humans
*Renal Insufficiency, Chronic/microbiology/blood
*Gastrointestinal Microbiome
Male
Female
*Biomarkers/blood
Middle Aged
Methylamines/blood
Cross-Sectional Studies
Aged
Cytokines/blood
Feces/microbiology
*Diet
Dietary Fiber
Adult
RNA, Ribosomal, 16S/genetics

@article {pmid41101217,
year = {2025},
author = {Liu, XL and Wu, SY and Zou, ZP and Xian, X and Wang, J and Min, L and Zhou, Y and Houf, K and Yu, Z},
title = {Characterization and intestinal pathogenicity of Proteus mirabilis isolated from broiler carcasses and processing environments.},
journal = {International journal of food microbiology},
volume = {445},
number = {},
pages = {111487},
doi = {10.1016/j.ijfoodmicro.2025.111487},
pmid = {41101217},
issn = {1879-3460},
abstract = {Proteus mirabilis, a well-known urinary tract pathogen, is increasingly recognized as a food safety concern due to its frequent detection in meat products, particularly poultry. Sporadic reports indicate gastrointestinal symptoms linked to P. mirabilis, but the relationship between its genome, antibiotic resistance, and variable pathogenicity remains unclear. In this study, 142 P. mirabilis isolates were collected from broiler carcasses and processing environments in wet markets and industrial facilities to assess contamination levels. Thirty-six representative isolates were characterized for genomic heterogeneity, antibiotic resistance, and virulence gene profiles using whole-genome sequencing and phenotypic susceptibility testing. Selected strains were further assessed for intestinal pathogenicity in a murine model. Broiler carcasses from wet markets had significantly higher contamination rates (80.77 %, 21/26) than industrial sources (41.67 %, 5/12), with all wet market samples (13/13) testing positive. Overall, 94.4 % of isolates were multidrug-resistant, with carcass isolates showing higher resistance than environmental isolates. Animal experiments demonstrated variable pathogenicity, including intestinal injury, villus disruption, epithelial shedding, goblet cell loss, inflammatory cytokine elevation, and gut dysbiosis. Dysbiosis induced by certain strains (e.g., R638) was linked to intestinal injury, as confirmed by fecal microbiota transplantation. These findings highlight P. mirabilis as a highly heterogeneous foodborne pathogen, emphasizing the need for targeted hygiene practices, particularly in wet market processing environments.},
}

@article {pmid41100443,
year = {2025},
author = {Shi, F and Zou, D and Zhang, L and Guo, N and Yu, J and Degen, AA and Tang, X and Ren, S and Ru, Y and Zheng, S and Zhang, Y and Wang, D},
title = {Increased urea nitrogen salvaging by a remodeled gut microbiota helps nonhibernating pikas maintain protein homeostasis during winter.},
journal = {PLoS biology},
volume = {23},
number = {10},
pages = {e3003436},
doi = {10.1371/journal.pbio.3003436},
pmid = {41100443},
issn = {1545-7885},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Nitrogen/metabolism ; *Urea/metabolism ; Seasons ; *Lagomorpha/metabolism/microbiology/physiology ; Homeostasis ; *Proteostasis/physiology ; Feces/microbiology ; Diet, Protein-Restricted ; Male ; Liver/metabolism ; Herbivory ; Fecal Microbiota Transplantation ; },
abstract = {Nitrogen balance is a major challenge for herbivores when consuming a low-nitrogen diet. Gut microbiota-mediated urea nitrogen recycling facilitates protein homeostasis during times of nitrogen deficiency, yet its relevance to wild nonhibernating small mammals remains unclear. Here, through a combination of isotope tracing, metagenomics, targeted short-chain fatty acid analysis, and fecal microbiota transplantation, we investigated the effects of protein restriction in winter on urea nitrogen recycling in plateau pikas (Ochotona curzoniae) of the Qinghai-Tibetan Plateau. Hepatic urea-cycle metabolism was downregulated during winter protein restriction, accompanied by increases in beneficial bacteria with ureolytic capacity (such as the genus Alistipes), gut urease activity, and urea transporters, and acetate production, with a consequent increase in nitrogen reincorporation into the pika's protein pool. Critically, supplementing a low-protein diet with yak fecal microbiota enhanced the ureolytic capacity by increasing Alistipes abundance, revealing a critical mechanism whereby interspecies horizontal microbial transfer between sympatric species enhances host protein homeostasis. Our results reveal a functional role for the gut microbiota in urea nitrogen recycling to maintain protein balance in winter-active herbivorous small mammals and contribute to our understanding of species coexistence and mammalian adaptation to high-altitude environments. Our findings establish that microbiota-driven urea nitrogen recycling is a key adaptive strategy for protein homeostasis in winter-active herbivores. This work provides new insights into the mechanisms of mammalian adaptation to high-altitude environments and the dynamics of interspecies coexistence.},
}

*Gastrointestinal Microbiome/physiology
Animals
*Nitrogen/metabolism
*Urea/metabolism
Seasons
*Lagomorpha/metabolism/microbiology/physiology
Homeostasis
*Proteostasis/physiology
Feces/microbiology
Diet, Protein-Restricted
Male
Liver/metabolism
Herbivory
Fecal Microbiota Transplantation

@article {pmid41098769,
year = {2025},
author = {Li, Y and Xin, Y and Zong, W and Li, X},
title = {The role of oral microbiota in digestive system diseases: current advances and perspectives.},
journal = {Journal of oral microbiology},
volume = {17},
number = {1},
pages = {2566403},
pmid = {41098769},
issn = {2000-2297},
abstract = {The oral microbiota is intimately linked to human health and various disease states. With the advent of the Human Microbiome Project, our comprehension of the oral microbiota has substantially improved. This microbial community is not only associated with a range of oral diseases, such as dental caries and periodontal diseases, but also with numerous digestive disorders, as demonstrated by recent clinical studies. Specific bacteria residing in the oral cavity, such as Porphyromonas gingivalis, Fusobacterium species and Streptococcus species, have been shown to translocate to the gastrointestinal tract, thereby establishing a potential connection between the oral and gut microbiota. The transfer and ectopic colonization of oral microbiota within the gastrointestinal tract may contribute to both the onset and exacerbation of gastrointestinal diseases. Following the principles of dysregulation characteristics, mechanism research and innovative treatment, this paper systematically reviews the association between the oral microbiota and various digestive system diseases. This paper explores how specific oral microbiota drive digestive system diseases mechanisms and evaluates treatments including probiotics, prebiotics, fecal microbiota transplantation, and targeted antimicrobial therapies. By clarifying the oral-gut microbiota-disease link, it highlights oral microbiota monitoring as a promising tool for early detection, diagnosis, and therapy.},
}

@article {pmid41097970,
year = {2025},
author = {Ma, Y and Huang, J and Zhuo, Q and Shen, S and Zhang, B and Wang, H and Zhang, J and Wang, O},
title = {[Impact of high-fat diet on intestinal fat absorption and fatty acid metabolism in rats transplanted with gut microbiota from hypertriglyceridemic individuals].},
journal = {Wei sheng yan jiu = Journal of hygiene research},
volume = {54},
number = {5},
pages = {757-762},
doi = {10.19813/j.cnki.weishengyanjiu.2025.05.008},
pmid = {41097970},
issn = {1000-8020},
mesh = {Animals ; Male ; *Diet, High-Fat/adverse effects ; Rats ; *Gastrointestinal Microbiome/physiology ; Rats, Sprague-Dawley ; *Fatty Acids/metabolism ; *Fecal Microbiota Transplantation ; *Intestinal Absorption ; *Hypertriglyceridemia/metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; Humans ; Feces/microbiology ; Lipid Metabolism ; },
abstract = {OBJECTIVE: To investigate the effects of fecal microbiota transplantation on fat absorption rate, fatty acid metabolic flux, and short-chain fatty acid production in germ-free Sprague-Dawley(SD) rats.

METHODS: Ten-week-old male germ-free SD rats were randomly grouped(5-6 rats/group) by body weight. Blank control: saline gavaged + germ-free basal diet. Normal control: colonized with normal-TG(≤1.7 mmol/L) human gut microbiota + germ-free basal diet. Two other groups: colonized with high-TG(>1.7 mmol/L) human gut microbiota, one on germ-free basal diet and the other on high-fat diet(40.5% fat energy). Day 0 marked colonization start. On Days 0, 2, 4, rats were gavaged with fecal bacteria(1 mL/100 g body weight). After 10-day adaptation, high-fat group started high-fat diet on Day 14. Feces were induced and collected aseptically on Days 0, 14, 21, 56, 77 for total fat(fat absorption rate), fatty acid profile, and short-chain fatty acids like butyric acid.

RESULTS: On Day 77, compared to blank control, normal control had lower body weight, fat absorption rate, and fecal palmitoleic and linoleic acids(P<0.05), but higher butyric, palmitic, arachidic, oleic, DHA, and stearic acids(P<0.05). High-TG group had higher body weight, fat absorption rate, and fecal palmitoleic and linoleic acids than normal control(P<0.05), with lower butyric, three saturated, and oleic acids(P<0.05). High-fat group had higher body weight, fat absorption rate, and fecal fatty acids than high-TG group(P<0.05). After Day 21, α-linolenic acid was undetectable in all groups.

CONCLUSION: In contrast to the positive regulation of lipid metabolism in rats by colonization with non-high-TG microbiota, colonization with high-TG microbiota disrupts lipid metabolism balance, inhibits the excretion of saturated fatty acids and oleic acid, reduces butyrate production, increases fat absorption rate, elevates the risk of obesity, and may synergize with a high-fat diet to exacerbate intestinal lipid metabolism disorders.},
}

Animals
Male
*Diet, High-Fat/adverse effects
Rats
*Gastrointestinal Microbiome/physiology
Rats, Sprague-Dawley
*Fatty Acids/metabolism
*Fecal Microbiota Transplantation
*Intestinal Absorption
*Hypertriglyceridemia/metabolism/microbiology
Fatty Acids, Volatile/metabolism
Humans
Feces/microbiology
Lipid Metabolism

@article {pmid41097199,
year = {2025},
author = {Dey, P},
title = {All That Glitters Ain't Gold: The Myths and Scientific Realities About the Gut Microbiota.},
journal = {Nutrients},
volume = {17},
number = {19},
pages = {},
doi = {10.3390/nu17193121},
pmid = {41097199},
issn = {2072-6643},
mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Dysbiosis/microbiology ; Probiotics ; Diet ; Fecal Microbiota Transplantation ; },
abstract = {Gut microbial modulation through diet is central to human health and disease. Despite tremendous effort in understanding the impact of nutrients and drugs on the gut microbiota, and attempts to develop dietary strategies that facilitate gut-beneficial effects, several erroneous gut microbiota-associated concepts remain prevalent in popular belief. This article discusses widespread misconceptions about the gut microbiota, contrasting them with contemporary scientific facts. In this article, ten prevalent myths, including the obsolete 10:1 bacteria-to-human-cell ratio, the reductive categorization of microbes as 'good' or 'bad', and the discredited universal biomarker status of the Firmicutes/Bacteroidetes ratio in relation to metabolic diseases, have been debunked. Essential facts highlighting the context-dependency of the microbiome, considerable inter-individual heterogeneity, and dynamic reactivity to dietary changes are discussed. This questions the assumptions that increased diversity always signifies health, that probiotics are intrinsically safe, that fecal microbiota transplantation is a universal remedy, or that leaky gut syndrome constitutes a clearly defined diagnosis. It is highlighted that eubiosis and dysbiosis do not possess uniform criteria, and microbiome-drug interactions are extremely individualized. The gut microbiota operates as a dynamic, adaptive ecosystem, necessitating sophisticated, evidence-based methodologies for study and therapeutic application, transcending simplistic misconceptions in favor of tailored insights and therapies.},
}

*Gastrointestinal Microbiome/physiology
Humans
Dysbiosis/microbiology
Probiotics
Diet
Fecal Microbiota Transplantation

@article {pmid41096928,
year = {2025},
author = {Yang, B and Wu, J and Hou, X and Bai, T and Liu, S},
title = {Memory in Misfire: The Gut Microbiome-Trained Immunity Circuit in Inflammatory Bowel Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
doi = {10.3390/ijms26199663},
pmid = {41096928},
issn = {1422-0067},
support = {2022YFC2504005//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Animals ; *Immunologic Memory ; Immunity, Innate ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Trained Immunity ; },
abstract = {Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. "Trained immunity"-the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors-maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut-bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome-immune-neuronal axis interactions, and host genetic variants modulating microbiome-immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Inflammatory Bowel Diseases/immunology/microbiology/therapy
Animals
*Immunologic Memory
Immunity, Innate
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Trained Immunity

@article {pmid41095952,
year = {2025},
author = {Soares Ferreira Júnior, A and Rodrigues da Silva, BF and Luiz da Silva, J and Trovão da Silva, M and Feliciano, JVP and Colturato, I and Barros, GMN and Scheinberg, P and Chao, NJA and de Oliveira, GLV},
title = {Unraveling the Intestinal Microbiota Conundrum in Allogeneic Hematopoietic Stem Cell Transplantation: Fingerprints, Clinical Implications and Future Directions.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/jcm14196874},
pmid = {41095952},
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/ ; #313190/2021-6//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
abstract = {Intestinal dysbiosis represents a critical determinant of clinical outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Distinct microbiota patterns represent potential prognostic biomarkers and therapeutic targets. However, the exponential growth in microbiota research and analytical complexity has created significant interpretive challenges for clinicians. This review provides a synthesis of current literature examining microbiota fingerprints and their clinical implications. We analyzed key studies evaluating the clinical implications of intestinal microbiota fingerprints in allo-HSCT. Additionally, we examined current therapeutic strategies for microbiota modulation and approaches for translating research findings into clinical practice. We identified three major microbiota fingerprints: (1) decreased intestinal microbiota diversity, (2) reduced abundance of short-chain fatty acid-producing bacteria, and (3) Enterococcus domination. These fingerprints are associated with critical clinical outcomes including overall survival, Graft-versus-host disease, transplant-related mortality, and infection-related complications. While fecal microbiota transplantation and dietary interventions appear promising, current studies suffer from limited sample sizes and lack standardized protocols. Despite significant advances in microbiota research, biological, methodological, and logistical challenges continue to hinder its clinical translation. Understanding microbiota fingerprints represents a promising avenue for improving allo-HSCT outcomes. However, successful clinical implementation requires standardized methodologies, mechanistic studies, and multi-center collaborations to translate research into actionable clinical tools.},
}

@article {pmid41094491,
year = {2025},
author = {Wang, Z and Zhou, L and Zheng, Y and Zhong, X and Huang, R and Sun, W and Wang, S and Li, W},
title = {Nuclear receptor Nr1d1 links sleep deprivation to intestinal homeostasis via microbiota-derived taurine.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1106},
pmid = {41094491},
issn = {1479-5876},
support = {2023YFC2705400//National Key R&D Rrogram of China/ ; 2021B1515420004//Guangdong Basic and Applied Basic Research Foundation/ ; 2025A03J4164//Huadu District Basic and Applied Basic Research Joint Funding Project/ ; GKLBCN-202501-01//Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University/ ; 202201020363//Science and Technology Projects in Guangzhou/ ; 2020A1515011031//Natural Science Foundation of Guangdong Province/ ; },
mesh = {Animals ; *Sleep Deprivation/microbiology/metabolism ; *Homeostasis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Taurine/metabolism/pharmacology ; *Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism ; Male ; Mice, Inbred C57BL ; Intestinal Mucosa/pathology/metabolism ; *Intestines/microbiology/pathology ; Mice ; Fecal Microbiota Transplantation ; Colon/pathology ; },
abstract = {BACKGROUND: Sleep deficiency significantly compromises human health, with the gut being particularly susceptible. However, the molecular mechanisms by which gut microbiota mediate sleep deprivation-induced intestinal dysfunction remain largely undefined. In this study, we employed a chronic sleep deprivation (CSD) mouse model to investigate the impact of sleep loss on intestinal integrity and microbial composition.

METHODS: The CSD mouse model was established using the modified multiple platform (rotating rod) method. Colon histomorphology was assessed by hematoxylin and eosin (HE) staining. Expression levels of barrier proteins (Occludin, Claudin-1) and circadian regulators (Nr1d1, Bmal1) were evaluated via Western blot or immunohistochemistry (IHC). Gut microbiota composition and stability were analyzed by 16S rRNA gene sequencing, and the causal role of microbiota in CSD-induced barrier damage was assessed through fecal microbiota transplantation (FMT). RNA sequencing (RNA-seq) of intestinal epithelial tissues identified differentially expressed genes and enriched pathways. Untargeted metabolomics was employed to investigate key differential metabolites (Taurine). Additionally, taurine was supplemented in vivo to explore its efficacy and mechanism in alleviating intestinal barrier damage in CSD mice.

RESULTS: CSD led to pronounced colon shortening and significant downregulation of the epithelial barrier proteins Occludin and Claudin-1, indicative of impaired intestinal barrier function. Moreover, CSD exacerbated symptoms of chemically induced colitis and induced gut microbiota dysbiosis. Mechanistically, FMT from CSD mice into antibiotic-treated recipients recapitulated intestinal inflammation, confirming the pathogenic role of the altered microbiota. Transcriptomic analysis revealed significant enrichment of genes involved in circadian rhythm pathways, notably a marked suppression of the circadian nuclear receptor Nr1d1, a key regulator of intestinal homeostasis. Complementary untargeted metabolomic profiling identified taurine as a microbiota-derived metabolite significantly reduced by CSD. In vivo taurine supplementation restored Nr1d1 expression, reinforced epithelial barrier integrity, and decreased pro-inflammatory cytokine production.

CONCLUSION: Together, these findings reveal a gut microbiota-taurine-Nr1d1 axis underlying sleep deprivation-induced intestinal barrier dysfunction, and suggest that therapeutic modulation of taurine levels or circadian pathways may offer novel strategies to prevent or treat sleep-related gastrointestinal disorders.},
}

Animals
*Sleep Deprivation/microbiology/metabolism
*Homeostasis/drug effects
*Gastrointestinal Microbiome/drug effects
*Taurine/metabolism/pharmacology
*Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism
Male
Mice, Inbred C57BL
Intestinal Mucosa/pathology/metabolism
*Intestines/microbiology/pathology
Mice
Fecal Microbiota Transplantation
Colon/pathology

@article {pmid41090775,
year = {2025},
author = {Baek, JS and Ma, X and Park, HS and Lee, DY and Kim, DH},
title = {Bifidobacterium longum P77 and Lactiplantibacillus plantarum P72 and Their Mix-Live or Heat-Treated-Mitigate Sleeplessness and Depression in Mice: Involvement of Serotonergic and GABAergic Systems.},
journal = {Cells},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/cells14191547},
pmid = {41090775},
issn = {2073-4409},
support = {RS-2024-00486802//the Commercialization Promotion Agency for R&D Outcomes (COMPA) grant/ ; 2017R1A5A2014768//National Research Foundation of Korea/ ; },
mesh = {Animals ; *Depression/therapy ; Mice ; *Serotonin/metabolism ; Humans ; Male ; *Bifidobacterium longum/physiology ; Probiotics/pharmacology ; Anxiety ; Hot Temperature ; gamma-Aminobutyric Acid/metabolism ; Mice, Inbred C57BL ; Stress, Psychological ; },
abstract = {Sleeplessness (insomnia) is a significant symptom associated with stress-induced depression/anxiety. In the present study, we selected Bifidobacterium longum P77, which increased serotonin production in corticosterone-stimulated SH-SY5Y cells, from the fecal bacteria collection of healthy volunteers and examined the effects of B. longum on depression, anxiety, and sleeplessness induced by immobilization stress or by transplantation of cultured fecal microbiota (cFM) from patients with depression. Orally administered B. longum P77 decreased depression/anxiety- and sleeplessness-like behaviors in immobilization stress-exposed mice. B. longum P77 reduced immobilization stress-induced corticosterone, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression and the cell population of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)[+] in the prefrontal cortex, while the expression levels of immobilization stress-suppressed IL-10, γ-aminobutyric acid (GABA), its receptor GABAARα1, serotonin, and its receptor 5-HT1AR increased. B. longum P77 also alleviated immobilization stress-induced colitis: it decreased TNF-α and IL-6 expression and increased IL-10 expression in the colon. Furthermore, B. longum P77, Lactiplantibacillus plantarum P72, and their combination decreased cFM- or immobilization stress-induced depression-, anxiety-, and sleeplessness-like behaviors. They also decreased cFM-induced, corticosterone, TNF-α, and IL-6 expression levels in the prefrontal cortex and colon, while increasing cFM- or immobilization stress-suppressed GABA, GABAARα1, serotonin, and 5-HT1AR expression levels in the prefrontal cortex. In particular, the combination of B. longum P77 and L. plantarum P72 (P7277) additively or synergistically alleviated depression-, anxiety-, and sleeplessness-like behaviors, along with their associated biomarkers. Heat-killed P7277 also alleviated immobilization stress-induced depression/anxiety- and sleeplessness-like symptoms. These results imply that L. plantarum P72 and/or B. longum P77 can mitigate depression/anxiety and sleeplessness by upregulating GABAergic and serotonergic systems, along with the suppression of NF-κB activation.},
}

Animals
*Depression/therapy
Mice
*Serotonin/metabolism
Humans
Male
*Bifidobacterium longum/physiology
Probiotics/pharmacology
Anxiety
Hot Temperature
gamma-Aminobutyric Acid/metabolism
Mice, Inbred C57BL
Stress, Psychological

@article {pmid41090697,
year = {2025},
author = {Moore, JE and Millar, BC},
title = {Improving health literacy and patient-directed knowledge of fecal microbiota transplantation (FMT) through analysis of readability: a cross sectional infodemiology study.},
journal = {Expert opinion on biological therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14712598.2025.2576509},
pmid = {41090697},
issn = {1744-7682},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used in geriatric medicine, including intestinal decolonization of antimicrobial-resistant bacterial pathogens and the treatment of inflammatory bowel disease, graft versus host disease and autism spectrum disorders. The aim of this study was to examine readability of patient-facing FMT information.

RESEARCH DESIGN AND METHODS: Readability was calculated using Readable software, examining (i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index and two text metrics [words/sentence, syllables/word] for 234 sources of FMT information, from four categories (abstracts/hospital information/patient-facing information/clinical trials).

RESULTS: Mean readability scores of FMT information for FRE and FKGL were 22.2 ± 1.2 (SEM)) (target > 60) and 14.8 ± 0.2 (target < 8), respectively, with mean words/sentence and syllables/word of 19.2 ± 0.4 and 2.0, respectively. There was no significant difference in readability between scientific abstracts and lay summaries. No information was found that had a readability of less than 7th grade (12-13 year olds).

CONCLUSION: Readability of FMT information for patients is poor, not reaching readability reference standards. Authors of FMT information should consider using readability calculators when preparing FMT information, so that the final material is within recommended readability reference parameters, to support the health literacy and treatment adherence of readers.},
}

@article {pmid41089557,
year = {2025},
author = {Chen, N and Zhang, M and Shi, B and Luo, X and Huang, R and Luo, Z and He, J and Xue, S and Li, N and Ling, Z and Guo, H and Xu, R and Liu, Y},
title = {Tirzepatide, a dual GLP-1 and GIP receptor agonist, promotes bone loss in obese mice via gut microbial-related metabolites.},
journal = {Journal of orthopaedic translation},
volume = {55},
number = {},
pages = {280-292},
pmid = {41089557},
issn = {2214-031X},
abstract = {BACKGROUND: As a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, Tirzepatide (TZP) is a recently approved medication for treating type 2 diabetes mellitus (T2DM) and obesity; however, the effect of TZP in bone remodeling remains unclear.

METHODS: 1. The effect of Tirzepatide on osteoblasts and osteoclasts was observed by inducing differentiation of bone marrow mesenchymal cells (BMSCs) in vitro. 2. Db/db mice were used as a pathological model to investigate the role of TZP on bone metabolism. After TZP intervention, the feces in the intestinal tract of mice were collected for 16s rRNA gene sequencing to select the candidate gut microbiota most related to bone mass, and the effects of gut microbiota on bone metabolism were verified through subsequent microbiota supplementation experiments. 3. Metabolomics was used to analyze the difference of fecal metabolites between mice with the candidate microbiota supplement and those without, and the effect of candidate metabolites on bone metabolism was verified by the in vitro intervention of differential metabolites in BMSCs induction differentiation experiments.

RESULTS: We found that TZP intervention resulted in a significant decrease in bone mass accrual in vivo. TZP was not indispensable to the differentiation of osteoblasts and osteoclasts in vitro. Bone and fat homeostasis were modulated by gut microbiota. We further demonstrated that the biodiversity of the gut microbiota in db/db mice was strikingly altered after TZP treatment. Lachnospiraceae, a key pro-osteogenic component of gut microbiota was significantly reduced. As a main metabolite of Lachnospiraceae, evodiamine played a role in suppressing osteoclastogenesis in vitro. Based on this, the transplantation of the Lachnospiraceae effectively ameliorated bone loss that was seen in db/db mice due to TZP treatment.

CONCLUSION: TZP administration leads to bone loss in the context of diabetes and obesity, and targeting the composition of gut microbiota may provide a potential way to protect bone health in type 2 diabetic patients treating with TZP.

This study indicates that TZP has a negative impact on bone mass, suggesting that clinical attention should be paid to the risk of further decline in bone mass after Tirzepatide treatment, and it is necessary to follow up on their bone metabolism. Additionally, the gut microbiota plays an important role in bone metabolism regulation, and supplementing with certain probiotics may have a preventive effect on bone mass reduction associated with TZP treatment. Our research provides a reference for the prevention and treatment of drug-related osteoporosis in patients with T2DM in the future.},
}

@article {pmid41089551,
year = {2025},
author = {Hearn, J and Malik, G and Stukalin, I and Panaccione, R and Ingram, RJM and Ma, C},
title = {Refractory Immune Checkpoint Inhibitor Colitis Treated With Biologics, Janus Kinase Inhibition, Plasma Exchange, and Fecal Microbiota Transplantation.},
journal = {ACG case reports journal},
volume = {12},
number = {10},
pages = {e01847},
pmid = {41089551},
issn = {2326-3253},
abstract = {Enterocolitis is a common immune-related adverse event associated with cancer immunotherapy. Current guidelines inform first-line pharmacologic management of immune checkpoint inhibitor-related enterocolitis; however, treatment in refractory cases is uncertain. We present a case of a 45-year-old woman with refractory immune checkpoint inhibitor-related enterocolitis requiring treatment with a combination of janus kinase inhibition, therapeutic plasma exchange, and fecal microbiota transplantation after failure of several lines of therapy. This is the first report of the combination of upadacitinib, plasma exchange, and fecal microbiota transplant for refractory enterocolitis.},
}

@article {pmid41089403,
year = {2025},
author = {Wang, J and Zhang, X and Cui, C and Li, M and Xie, Z and Yang, L and Ding, D and Li, X and Zhao, M},
title = {Gut Microbiota and Metabolite Changes Induced by Tacrolimus: Implications for Skin Transplant Immunology in Mice.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {14059-14073},
pmid = {41089403},
issn = {1178-7031},
abstract = {BACKGROUND: Tacrolimus is the most widely used immunosuppressive therapy in solid organ transplantation. However, whether it can inhibit transplant graft rejection by altering the composition and metabolism of gut microbiota remains unclear.

METHODS: In this study, a skin transplantation mouse model was established to explore the effects of tacrolimus on gut microbiota and its metabolites. Additionally, we investigated the protective effect and potential mechanism of feces from mice treated with tacrolimus on skin allografts.

RESULTS: Tacrolimus did not significantly affect gut microbiota α-diversity but altered β-diversity, with specific changes in microbial composition. LEfSe analysis identified 19 microbial taxa with reduced and 12 with elevated relative abundance in the Tac group (mice treated with tacrolimus) compared to the Ctrl group (mice with no treatment). Metabolomic analysis identified 33 differential fecal metabolites (17 upregulated and 16 downregulated) in the Tac group compared to the Ctrl group. FMT from tacrolimus-treated mice significantly prolonged skin allograft survival, reduced inflammatory cell infiltration, and improved graft histopathology. This protective effect was associated with increased Treg cell proportions and decreased Th17 cell proportions in draining lymph nodes and mesenteric lymph node.

CONCLUSION: Overall, our data may provide a basis for establishing gut microbiota-based therapies for allograft rejection.},
}

@article {pmid41088420,
year = {2025},
author = {Zhu, JH and Wu, LP and Deng, L and Zang, SG and Li, XB and Chen, X and Yu, JX},
title = {Gut microbiota and metabolism in systemic lupus erythematosus: from dysbiosis to targeted interventions.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {971},
pmid = {41088420},
issn = {2047-783X},
support = {No.YK2023130//The Medical Research Project of Yancheng Health Commission/ ; No.2024LZ006//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; 2024LZ008//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; No.YCBE202475//The Special Fund Project of Yancheng Science and Technology Bureau/ ; },
mesh = {Humans ; *Lupus Erythematosus, Systemic/metabolism/microbiology/therapy ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/metabolism/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiorgan involvement, with pathogenesis closely linked to that of gut dysbiosis and metabolic disturbances. Studies indicate that SLE patients exhibit significantly reduced gut microbial diversity, increased abundance of pathogenic bacteria, and decreased beneficial bacteria. Dysbiosis exacerbates disease progression by disrupting the intestinal barrier, triggering autoimmune responses, and promoting proinflammatory cytokine release. Metabolomic analyses further reveal that SLE is associated with dysregulated amino acid metabolism, reduced short-chain fatty acids, and disrupted lipid homeostasis, which correlate with disease activity, renal injury, and increased atherosclerosis risk. Emerging microbiota-targeted interventions, such as fecal microbiota transplantation (FMT), probiotics/prebiotics, phage therapy, and dietary modifications, demonstrate promising therapeutic potential by restoring microbial balance, enhancing immune regulation, and improving metabolic homeostasis. This review systematically summarizes the alterations in gut microbiota and metabolism in SLE, their critical roles in disease progression, diagnosis, and pathogenesis, and explores the clinical value of microbial-targeted strategies in improving SLE outcomes.},
}

Humans
*Lupus Erythematosus, Systemic/metabolism/microbiology/therapy
*Gastrointestinal Microbiome
*Dysbiosis/therapy/metabolism/microbiology
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid41087864,
year = {2025},
author = {Chen, H and Wang, Z and Su, W and Li, S and Ye, Q and Zhang, G and Zhou, X},
title = {Helicobacter pylori infection impairs glucose homeostasis through gut microbiota dysbiosis.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {663},
pmid = {41087864},
issn = {1471-2180},
support = {82100594//National Natural Science Foundation of China,China/ ; },
abstract = {BACKGROUND: Epidemiological data show that Helicobacter pylori (H. pylori) infection is not only the most important risk factor for gastric cancer, but is also associated with poor glycemic control in patients with diabetes. However, the direct causal and functional relationship between H. pylori infection and dysglycemia is unclear.

METHOD: A retrospective cohort study was conducted to examine the association between H. pylori infection and glycemic levels in individuals with Type 2 diabetes. C57BL/6 diabetic mice were infected with H. pylori, and the resulting changes in colonic inflammation and intestinal Glucagon-like peptide-1 (GLP-1) secretion were thoroughly examined using immunohistochemistry, RNA sequencing, metagenomic sequencing, and targeted metabolomics. The microbial and metabolomics profiles were analyzed and compared in antibiotic-treated mice through fecal transfer experiments.

RESULTS: H. pylori infection aggravated insulin resistance in diabetic individuals and mice. We identified a unique H. pylori-induced epithelial inflammation and reduced intestinal GLP-1 secretion in the colon. H. pylori infection also interrupts the normal microbial composition in the colon, leading to a decrease in SCFA-producing bacteria and a reduction in acetic and propionate acids. Similar changes were observed in antibiotic-treated mice after receiving fecal transplants from H. pylori-infected diabetic mice. In vitro studies revealed that the intestinal flora of H. pylori-positive diabetic mice inhibited proglucagon transcription, cAMP levels, and GLP-1 secretion in colonic endocrine cells, with SCFA supplementation reversing this effect on GLP-1 production. These microbial, metabolic, and GLP-1 alterations were also seen in antibiotic-treated mice after receiving fecal transplants from H. pylori-infected diabetic mice. H. pylori eradication with antibiotics improved glucose metabolism and GLP-1 secretion to levels comparable to uninfected controls.

CONCLUSION: Our studies offer evidence that H. pylori infection significantly contributes to the progression of glucose impairment and insulin resistance. Therefore, incorporating H. pylori status into preventive strategies for diabetes should be taken into account. (Chinese Clinical Trial Registry Center, ChiCTR2200063489, Registered 08 September 2022, https://www.chictr.org.cn/showproj.html?proj=178102).},
}

@article {pmid41087029,
year = {2025},
author = {Tu, D and Lu, C and Guo, J and Chen, Q and Li, X and Wang, Y and Cheng, L and Jiang, H and Jian, J and Ge, Y and Hou, Z and Feng, X and Feng, Y and Zhou, J and Lei, Y and Diao, H and Ran, L and Zhou, Y and Xu, Z and Zhou, J and Tang, B and Yang, S},
title = {Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-HT production.},
journal = {Clinical and molecular hepatology},
volume = {},
number = {},
pages = {},
doi = {10.3350/cmh.2025.0577},
pmid = {41087029},
issn = {2287-285X},
abstract = {BACKGROUND/AIMS: Cholestatic liver disease (CLD) is a pathological condition characterized by impaired bile formation, secretion, and excretion. However, the key pathophysiological mechanisms of CLD remain elusive, and therapeutic efficacy is unsatisfactory.

METHODS: We administered berberine (BBR) or dihydroberberine (dhBBR) in bile duct ligation-, ANIT-, and mdr2-/- CLD mouse models to evaluate the anti-CLD effect. We conducted fecal microbiota transplantation to determine the role of gut microbiota in BBR's effect. We conducted a randomized, controlled clinical trial to evaluate the effects of BBR in patients with CLD.

RESULTS: Oral BBR alleviates cholestatic liver injury in multiple mouse models. Gut microbes can transform BBR into dhBBR, which suppresses 5-HT production in gut enterochromaffin cells by antagonizing tryptophan hydroxylase 1 (TPH1) activity and downregulating Tph1 transcription. This further ameliorates CLD by interrupting the 5-HT/5HTR axis. A clinical study validated that BBR improved blood biochemical indicators in patients with CLD and decreased 5-HT levels.

CONCLUSIONS: BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use.},
}

@article {pmid41086122,
year = {2025},
author = {Peng, W and Fan, X and Shi, H and Jiang, Y and Fan, L and Xing, Y and Peng, Y and He, Y and Zou, W and Jiang, M},
title = {Gut Microbiota and Chemotherapy-Induced Gastrointestinal Toxicity: Mechanisms and Intervention Strategies.},
journal = {Digestive diseases (Basel, Switzerland)},
volume = {},
number = {},
pages = {1-22},
doi = {10.1159/000548922},
pmid = {41086122},
issn = {1421-9875},
abstract = {BACKGROUND: Cancer remains a leading cause of mortality worldwide. Chemotherapy serves as a cornerstone of cancer treatment, providing significant benefits in tumor control and survival. However, its therapeutic efficacy is often compromised by gastrointestinal toxicity, which impairs quality of life and may necessitate treatment modifications. Disruption of the gut microbiota has been recognized as a key factor in the development of these toxicities.

SUMMARY: This review synthesizes evidence on how chemotherapeutic agents disrupt gut microbial balance and exacerbate gastrointestinal toxicity through epithelial barrier damage, inflammatory activation, and metabolic disturbance. It also examines diverse interventions, including dietary modifications, probiotics, prebiotics, synbiotics, traditional herbal medicines, and fecal microbiota transplantation, that aim to restore microbial homeostasis and reduce gastrointestinal injury.

KEY MESSAGES: This review provides a symptom‑oriented framework linking specific clinical manifestations of chemotherapy‑related gastrointestinal toxicity with underlying microbial alterations. It further integrates emerging evidence across nutritional, microbial, and herbal approaches, emphasizing shared therapeutic pathways and highlighting prospects for personalized microbiota‑based strategies to improve treatment tolerance and patient outcomes.},
}

@article {pmid41085348,
year = {2025},
author = {Zhang, S and Wu, Z and Zhang, S and Ru, Y and Wang, Q and Tong, H and Qin, Q and Yan, Q and Li, Z and Wu, G},
title = {The intricate microbial-gut-brain axis in Alzheimer's disease: a review of microbiota-targeted strategies.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo03139g},
pmid = {41085348},
issn = {2042-650X},
abstract = {The microbiome-gut-brain axis (MGBA) has emerged as a potential focus for the enhancement of cognitive abilities and the improvement of Alzheimer's disease (AD). Probiotics and prebiotics can improve the imbalance of gut microbiota to alleviate AD symptoms. Current research on probiotics/prebiotics and brain function mainly focuses on metabolic pathways such as those involving microbial metabolites like lipopolysaccharides and short-chain fatty acids, as well as immune pathways that regulate inflammation in the gut and brain. However, the roles played by endocrine and neural pathways remain less explored and warrant further attention. This review explores the intricate mechanisms of gut-brain communication within the MGBA, and especially systematically elaborates on the specific mechanisms of the endocrine pathway (impact of gut-derived and exogenous hormones on brain function) and the neural pathway (regulation of brain function by the sympathetic and parasympathetic systems). It also emphasizes the specific changes in gut microbiota noted in individuals with AD. Additionally, it examines the beneficial effects of probiotics, prebiotics, synbiotics, and postbiotics for cognitive function, reviewing their advancements in preclinical research, clinical trials, and commercial applications. Furthermore, this review delves into novel gut microbiota-related strategies to promote brain health, including antibiotics, certain gut-targeted inhibitors or agonists, fecal microbiota transplantation, whole microbiome transplantation, viral microbiota transplantation, genetically engineered bacteria, and bacteriophage-based in situ intestinal microbiome engineering. Ultimately, this review aims to advance the therapeutic application of gut microbiota-targeted strategies in AD.},
}

@article {pmid41081988,
year = {2025},
author = {Bhat, A and Mansoor, A and Fatima, M and Kumar, A and Mari, T and Ali, A and Bakht, K and Dad, A and Zahra, R and Makhija, V and Southwick, FS},
title = {Safety and efficacy of fecal microbiota transplantation versus antibiotics for treating clostridioides difficile infection: systematic review and meta-analysis.},
journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology},
volume = {},
number = {},
pages = {},
pmid = {41081988},
issn = {1435-4373},
abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is a persistent clinical challenge due to the high rate of relapse following treatment with standard antibiotics. Fecal microbiota transplantation (FMT) has emerged as a promising alternative, with comparable results. Aiming to restore intestinal microbial balance and reduce recurrence. Comparative evidence on the efficacy and safety of FMT versus antibiotics remains variable across studies, warranting a comprehensive synthesis to guide clinical decision-making.

AIM: This systematic review and meta-analysis aims to present an updated comparison of the effectiveness and safety of FMT versus Vancomycin/ fidaxomicin in patients with CDI.

METHODS: A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted to identify randomized controlled trials comparing FMT with standard antibiotic therapy for recurrent CDI. Primary outcomes included resolution of infection, recurrence, mortality, and adverse events. A random-effects model was used to calculate risk ratios with 95% confidence intervals. Statistical heterogeneity was assessed using the I-squared statistic. The quality of the included studies was evaluated using the Cochrane Risk of Bias version 2 and ROBINS-1 tools.

RESULTS: A total of 9 clinical trials involving 759 patients were included. FMT was significantly more effective in resolving CDI compared to antibiotic therapy, with a risk ratio (RR) of 1.51 (95% CI: 1.29 to 1.78). Recurrence rates were significantly lower in the FMT group, with a RR of 0.38 (95% CI: 0.29 to 0.50). Mortality did not differ significantly between groups (RR = 0.95). Adverse events (AEs) were comparable between FMT and antibiotics, and no serious AEs directly related to FMT were reported. In the subgroup analysis, the lower GI route adminstration showed significant results (p = 0.02) for both recurrence and resolution of CDI.

CONCLUSION: FMT is more effective than standard antibiotic therapy for achieving resolution and reducing recurrence in patients with recurrent CDI.},
}

@article {pmid41081080,
year = {2025},
author = {Bzdyra, M and Tulewicz-Marti, EM and Przepióra, A and Lewandowski, K and Rydzewska, G},
title = {Efficacy and safety of faecal microbiota transplantation (FMT) in recurrent Clostridioides difficile infection: results of a single-centre retrospective study.},
journal = {Przeglad gastroenterologiczny},
volume = {20},
number = {3},
pages = {330-334},
pmid = {41081080},
issn = {1895-5770},
abstract = {INTRODUCTION: Studies have indicated the high effectiveness of faecal microbiota transplantation (FMT) in the treatment of recurrent Clostridioides difficile infection (rCDI). However, there is still a lack of data from different subpopulations regarding FMT and the factors related to it.

AIM: The aim of the study was to retrospectively evaluate the efficacy and safety of FMT in rCDI.

MATERIAL AND METHODS: In all cases, FMT was performed using a nasoenteric tube. A good response following a single FMT was considered an improvement, whereas requiring more than one FMT was considered a suboptimal response.

RESULTS: In the analysed period, FMT was performed on a total of 98 patients, including 74 with rCDI (of whom 23 received 2 FMTs, 6 received 3 FMTs, and 1 received 5 FMTs). The average age of the patients was 68 years. 42 (56%) patients were women, 41 (55.4%) had previously used antibiotics, 2 (2.7%) had used steroids, and 4 (5.4%) had used proton pump inhibitors (PPI). Following the first FMT procedure, clinical improvement was observed in 44 (59.4%) patients. The odds of a suboptimal effect of the therapy (needing more than 1 FMT) were associated with prior use of metronidazole. Among all analysed factors, cardiovascular risk factors (such as hypertension and hyperlipidaemia) were associated with a threefold increased likelihood of requiring more than 1 FMT (p = 0.038).

CONCLUSIONS: In our study, FMT was found to be an effective and safe treatment of recurrent CDI. Use of metronidazole was identified as a risk factor for a suboptimal response to FMT in the studied cohort.},
}

@article {pmid41080577,
year = {2025},
author = {Wang, Z and Yu, J and Liu, Y and Gong, J and Hu, Z and Liu, Z},
title = {Role of the microbiota-gut-lung axis in the pathogenesis of pulmonary disease in children and novel therapeutic strategies.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1636876},
pmid = {41080577},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Child ; *Lung/immunology/microbiology/metabolism ; *Lung Diseases/therapy/microbiology/immunology/etiology/metabolism ; Dysbiosis ; Animals ; Fatty Acids, Volatile/metabolism ; },
abstract = {Emerging evidence highlights the microbiota-gut-lung axis (MGLA) as a pivotal regulator of pediatric respiratory health, yet mechanistic insights are lacking and therapeutic applications remain unclear. This review synthesizes cutting-edge findings to delineate how gut microbiota-derived metabolites, particularly short-chain fatty acids (SCFAs), orchestrate pulmonary immunity and disease pathogenesis in children. Leveraging multi-omics integration (metagenomics, metabolomics, transcriptomics), emerging studies have uncovered novel microbe-host interactions driving immune dysregulation in asthma, pneumonia, and cystic fibrosis. A comprehensive map of gut-lung crosstalk has been established across these conditions. Current studies suggest that early-life gut dysbiosis, shaped by delivery mode, antibiotics, and diet, disrupts SCFA-mediated immune homeostasis, amplifying T-helper 2 cell inflammation and impairing alveolar macrophage function. Crucially, we identified disease-specific microbial signatures (e.g., depletion of Lachnospira and Faecalibacterium in asthma) and demonstrated that fecal microbiota transplantation and probiotic interventions restore microbial balance, attenuating airway inflammation in preclinical models. This work pioneers the translation of MGLA insights into precision medicine strategies, highlighting dietary modulation and microbial therapeutics as viable alternatives to conventional treatments. By bridging microbial ecology and immune dynamics, our findings provide actionable biomarkers for early diagnosis and personalized interventions, addressing critical gaps in pediatric respiratory disease management. The integration of multi-omics frameworks not only advances mechanistic understanding but also positions the MGLA as a transformative target in reducing global childhood morbidity. Future research must prioritize longitudinal studies and clinical trials to validate these innovations, ultimately redefining therapeutic paradigms for GLA-driven pathologies.},
}

Humans
*Gastrointestinal Microbiome/immunology
Child
*Lung/immunology/microbiology/metabolism
*Lung Diseases/therapy/microbiology/immunology/etiology/metabolism
Dysbiosis
Animals
Fatty Acids, Volatile/metabolism

@article {pmid41080562,
year = {2025},
author = {Zhu, Z and Cheng, Y and Liu, X and Xu, X and Ding, W and Ling, Z and Liu, J and Cai, G},
title = {The microbiota-gut-brain axis in depression: unraveling the relationships and therapeutic opportunities.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1644160},
pmid = {41080562},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Depression/therapy/microbiology/metabolism/etiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Brain-Gut Axis ; },
abstract = {Depression, a highly prevalent and relapsing mental disorder, exacts profound personal and socioeconomic tolls globally, warranting urgent scientific and clinical attention. Emerging evidence from both preclinical models and human clinical investigations has established the microbiota-gut-brain axis (MGBA) as a critical determinant in depression pathogenesis. This intricate bidirectional network integrates gut microbiota with central nervous system function, influencing mental health through mechanisms previously underrecognized. This review systematically synthesizes gut microbiota alterations associated with depression and their impacts on neuroendocrine, neuroimmune, and metabolic pathways. Advanced therapeutic strategies targeting the MGBA are discussed, including probiotics, fecal microbiota transplantation, and artificial intelligence-enabled microbiome interventions for depression management. While challenges in standardization, mechanistic understanding, efficacy and safety remain, MGBA-centered approaches offer a promising shift toward microbiota-based diagnostics and personalized treatments for depression.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Depression/therapy/microbiology/metabolism/etiology
*Brain/metabolism
Animals
Fecal Microbiota Transplantation
Probiotics/therapeutic use
*Brain-Gut Axis

@article {pmid41080326,
year = {2025},
author = {Qureshi, U and Bajwa, A and Aslam, Z and Aggrey, A and Nawaz, UH and Ul Ain, Q},
title = {Gut Microbiota Modulation in Type 2 Diabetes and Cardiometabolic Risk: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92020},
pmid = {41080326},
issn = {2168-8184},
abstract = {Cardiometabolic complications related to type 2 diabetes mellitus (T2DM) are often due to changes in the gut microbiota. The review analyzed studies looking at the effects of probiotics, prebiotics, high-fiber diets, and fecal microbiota transplantation (FMT) on glucose levels and heart and metabolic health in individuals either having T2DM or being at risk. The review followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The literature was searched using text terms and controlled vocabulary, employing Boolean operators "AND," "OR," and various combinations across PubMed, Embase, and the Cochrane Library. Open-access, full-text English papers from 2005 to 2025, including those authored by people, were searched. The quality was assessed using the Risk of Bias 2.0 (RoB 2.0) tool, and the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Fifteen randomized controlled trials (RCTs) were analyzed for methodological quality, with three categorized as having a high risk of bias (RoB). The GRADE tool categorized two high RoB RCTs as "low quality." However, two RCTs had low RoB and were classified as "high quality." Ten RCTs had uncertain RoB, lowering the evidence by one point to "moderate quality." A comprehensive review of RCTs was conducted to assess outcomes related to glycemic parameters (e.g., glycated hemoglobin (HbA1c), fasting glucose), lipid profiles, inflammatory markers, anthropometric measures, and gut microbiota composition. Interventions included probiotic and prebiotic supplementation, high-fiber or Mediterranean-style diets, and FMT. Probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis significantly improved lipid profiles by reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol. High-fiber diets consistently lowered fasting blood glucose, HbA1c, triglycerides, and LDL-C while elevating high-density lipoprotein cholesterol (HDL-C) and beneficial short-chain fatty acid (SCFA)-producing bacteria. Anti-inflammatory effects were observed across interventions, notably with probiotics and polyphenol-rich Mediterranean diets, which reduced tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and other inflammatory cytokines. The Green-Mediterranean diet significantly improved weight, insulin resistance, and Framingham risk scores. Novel mechanisms involving SCFAs and bile acid metabolism were also identified as key modulators of host metabolic response. Microbiota-based interventions offer promising avenues for glycemic control and cardiometabolic risk reduction in patients with T2DM.},
}

@article {pmid41080149,
year = {2025},
author = {Xu, H and Li, S and Liu, S and Zuo, YG},
title = {A Conceptual Review of Gut, Skin, and Oral Microbiota in Autoimmune Bullous Diseases: From Dysbiosis to Therapeutic Potential.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {13925-13943},
pmid = {41080149},
issn = {1178-7031},
abstract = {Autoimmune bullous diseases (AIBDs), including pemphigus and bullous pemphigoid, are chronic inflammatory skin disorders characterized by dysregulated immune responses mediated by autoantibodies that target adhesion molecules in the skin and mucous membranes. Emerging evidence highlights the pivotal role of host microbiota dysbiosis in AIBDs pathogenesis, offering novel insights into disease mechanisms and therapeutic strategies. This review systematically synthesizes the current findings on gut, skin, and oral microbiota alterations in AIBDs, emphasizing their contributions via the gut-skin axis, microbial metabolites, and pathogen-host interactions. Key innovations include uncovering how specific pathogenic and commensal microbiota influence disease progression through intriguing skin inflammation and direct barrier impairment. Notably, while some microbiota changes overlap with other dermatoses, AIBDs exhibit distinct microbial signatures associated with their unique autoimmune mechanisms targeting adhesion molecules. Furthermore, we explore microbiota-targeted therapies, such as antibiotics, probiotics, and fecal microbiota transplantation, and demonstrate their potential to restore microbial homeostasis and improve clinical outcomes. By integrating multi-omics evidence and clinical data, this review bridges mechanistic insights with translational applications, proposing microbiota modulation as a promising adjunctive therapy for AIBDs. Our analysis identifies critical research gaps, including the need for longitudinal studies and personalized microbial interventions, positioning this review at the forefront of microbiome-inflammation-autoimmunity research.},
}

@article {pmid41078532,
year = {2025},
author = {Taha, H and Issa, A and Muhanna, Z and Al-Shehab, M and Wadi, T and Awamleh, S and Ateiwi, YA and Abusido, M and Berggren, V},
title = {Microbiota-based interventions for autism spectrum disorder: a systematic review of efficacy and clinical potential.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1648118},
pmid = {41078532},
issn = {1664-302X},
abstract = {PURPOSE: Autism spectrum disorder (ASD) is increasingly linked to gut microbiota imbalances, influencing both behavioral and gastrointestinal (GI) symptoms. This systematic review assesses the efficacy of microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), in improving ASD-related symptoms, aiming to provide insights into their therapeutic potential and inform future clinical applications.

METHODS: A comprehensive systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD42024615043). A structured literature search was performed in PubMed, Cochrane Library, and Scopus to identify peer-reviewed English-language studies. Eligible studies included randomized controlled trials (RCTs), non-randomized trials (NRTs), and retrospective studies assessing the impact of microbiota-based interventions on ASD-related behavioral and GI outcomes. Two independent reviewers conducted study selection, data extraction, and quality assessment using standardized risk-of-bias tools.

RESULTS: 33 studies were included, consisting of 16 RCTs, 14 NRTs, and 3 retrospective studies. Among them, 15 assessed probiotics, 4 prebiotics, 5 synbiotics, and 9 FMT. Probiotics showed moderate behavioral improvements in ASD, with multi-strain formulations being more effective than single strains. Prebiotics and synbiotics yielded mixed results, with some studies indicating benefits in behavioral and GI symptoms. FMT demonstrated the most consistent and sustained improvements in both ASD-related behaviors and GI function. Adverse events were minimal, primarily involving transient GI symptoms.

CONCLUSION: Microbiota-targeted interventions, particularly FMT, hold promise for managing ASD symptoms, though probiotics, prebiotics, and synbiotics present variable efficacy. Standardized protocols, larger controlled trials, and personalized microbiome-based approaches are necessary to refine these therapeutic strategies and enhance clinical applicability.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024615043, identifier CRD42024615043.},
}

@article {pmid41078530,
year = {2025},
author = {Li, R and Hu, Y and Liu, Y and Tan, X},
title = {Fecal microbiota transplantation augments 5-fluorouracil efficacy in pancreatic cancer via gut microbiota modulation.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1548027},
pmid = {41078530},
issn = {1664-302X},
abstract = {BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options due to rapid tumor progression and poor prognosis. Fecal Microbiota Transplantation (FMT) has emerged as a promising approach to modulate gut microbiota, potentially enhancing the efficacy of conventional treatments.

OBJECTIVES: This study evaluates the combined effects of FMT and 5-fluorouracil (5FU) on gut microbiota composition, pancreatic tumor growth, and systemic immune responses in a murine model.

METHODS: One hundred female C57BL/6 mice aged 6-8 weeks were randomly divided into five groups (n = 20 each): Sham, Model, FMT, 5FU, and FMT + 5FU. Pancreatic tumors were induced via orthotopic implantation of Pan02 cells. FMT was administered orally (0.2 g fecal material) three times per week, starting 2 weeks before tumor implantation. 5FU was administered intraperitoneally at 25 mg/kg body weight twice weekly, beginning one-week post-tumor implantation. Gut microbiota was analyzed via 16S rRNA gene sequencing of fecal samples after 10-week cell implantation. Tumor volumes were measured, and serum cytokine levels were assessed. Short-chain fatty acids (SCFAs) in blood and feces using gas chromatography-mass spectrometry (GC-MS).

RESULTS: The FMT + 5FU group exhibited the smallest average tumor volume, significantly smaller than the Model (p < 0.0001) and 5FU groups (p = 0.005). FMT alone reduced tumor volume compared to the Model group (p < 0.0001). Gut microbiota analysis revealed increased α diversity in the FMT group compared to the Model group (p < 0.0001). The FMT + 5FU group showed a significant reduction in cytokine levels, including TNF-α (p = 0.0001) and IL-6 (p = 0.012) and increased IL-10 level (p < 0.001), compared to the Model group. Plasma and fecal SCFA concentrations were significantly higher in both FMT and FMT + 5FU groups relative to the Model group (p < 0.001). Additionally, the FMT + 5FU group had the highest survival rate (50%) after 10-week cell implantation, compared to the Model group (15%).

CONCLUSION: FMT significantly enhances the efficacy of 5FU in reducing pancreatic tumor growth through gut microbiota modulation.},
}

@article {pmid41078364,
year = {2025},
author = {Yu, J and Liu, Z and Wang, Y and Zhou, Y and Liu, W and Wang, T and Xie, Q and Tian, H and Xu, Y and Wang, M and Zhao, F and Wang, L and Zhang, G and Chen, D and Gao, L and Pan, T},
title = {Propionic acid mediates the renoprotective effects of fecal microbiota transplantation against ischemia-reperfusion injury via upregulating GPR43.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1616164},
pmid = {41078364},
issn = {2235-2988},
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Rats, Sprague-Dawley ; *Reperfusion Injury/therapy/prevention & control ; *Propionates/metabolism/pharmacology ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; Rats ; Disease Models, Animal ; Kidney/pathology ; Male ; Guinea Pigs ; *Acute Kidney Injury/therapy/prevention & control ; Apoptosis/drug effects ; Up-Regulation ; Signal Transduction ; },
abstract = {INTRODUCTION: Kidney ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), characterized by aggravated inflammation and apoptosis following reperfusion. This study aimed to investigate the protective effects and mechanisms of fecal microbiota transplantation (FMT) in a rat model of kidney IRI.

METHODS: Sprague-Dawley rats(SDRs) subjected to 45 minutes of bilateral renal ischemia followed by reperfusion were prophylactically treated with FMT derived from guinea pigs or supplemented with propionic acid. Renal function, histopathology, inflammatory markers, apoptosis, proliferation, and gut microbiota composition were systematically evaluated.

RESULTS: The results demonstrated that FMT attenuated kidney IRI by remodeling the gut microbiota to enhance propionic acid production, which subsequently modulated inflammation and apoptosis via GPR43 signaling.

CONCLUSIONS: These findings provide novel insights into microbiota-targeted therapeutic strategies for kidney IRI and highlight propionic acid as a potential therapeutic agent.},
}

Animals
*Fecal Microbiota Transplantation/methods
Rats, Sprague-Dawley
*Reperfusion Injury/therapy/prevention & control
*Propionates/metabolism/pharmacology
*Receptors, G-Protein-Coupled/metabolism/genetics
Gastrointestinal Microbiome/drug effects
Rats
Disease Models, Animal
Kidney/pathology
Male
Guinea Pigs
*Acute Kidney Injury/therapy/prevention & control
Apoptosis/drug effects
Up-Regulation
Signal Transduction

@article {pmid41078360,
year = {2025},
author = {Gu, X and Tang, J and Chen, C},
title = {Efficacy of gut microbiota-targeted therapies in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1627406},
pmid = {41078360},
issn = {2235-2988},
mesh = {Humans ; *Parkinson Disease/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Randomized Controlled Trials as Topic ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; Synbiotics/administration & dosage ; },
abstract = {OBJECTIVE: This study aimed to investigate the efficacy of gut microbiota (GM)-targeted therapies in treating Parkinson's disease (PD).

METHODS: Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane, and WOS from database inception to June 2025. The eligible RCTs employed GM-targeted therapies, including antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT), as adjunct treatments for PD. Data were pooled using a random-effects model, and the effect sizes were expressed as standardized mean differences (SMDs). In addition, the quality of evidence for all outcomes was assessed using the GRADE framework.

RESULTS: This study demonstrated that GM-targeted therapies significantly improved PD outcomes, including Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) III (SMD: -0.34, 95%CI: -0.57 to -0.11, P = 0.004), bowel movements (BMs) (SMD: 1.27, 95%CI: 0.35 to 2.2), use of laxatives (SMD: -0.33, 95% CI: -0.65 to -0.02), malondialdehyde (MDA) (SMD: -0.69, 95%CI: -1.23 to -0.15) indicators. However, there were no significant improvements in MDS-UPDRS I (SMD: -0.64, 95%CI: -1.42 to 0.13), MDS-UPDRS II (SMD: -0.28, 95%CI: -0.70 to 0.14), MDS-UPDRS IV (SMD: -0.08, 95% CI: -0.82 to 0.66), Mini-Mental State Examination (MMSE) (SMD: -0.01, 95% CI: -0.30 to 0.29), Montreal Cognitive Assessment (MoCA) (SMD: 0.04, 95%CI: -0.53 to 0.60), non-motor symptom scale (NMSS) (SMD: -0.11, 95%CI: -0.94 to 0.72), Parkinson's Disease Questionnaire-39 (PDQ-39) (SMD: -0.19, 95%CI: -0.58 to 0.20), total antioxidant capacity (TAC) (SMD: 0.29, 95%CI: -0.04 to 0.62), glutathione (GSH) (SMD: 0.51, 95%CI: -0.02 to 1.03), and Geriatric Depression Scale-15 (GDS-15) (SMD: -0.37, 95%CI: -0.87 to 0.12).

CONCLUSION: GM-targeted therapies may improve motor symptom scores (as measured by MDS-UPDRS III), alleviate constipation, and reduce blood malondialdehyde levels in PD patients. However, they did not significantly impact the scores for cognitive function, PD neuropsychiatric, behavioral, and emotional symptoms, and activities of daily living in this analysis. Given the inherent limitations of the included studies (such as small sample sizes and heterogeneity), future large-scale and rigorously designed RCTs are needed to validate these preliminary findings.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024606415.},
}

Humans
*Parkinson Disease/therapy/microbiology
*Gastrointestinal Microbiome/drug effects
Randomized Controlled Trials as Topic
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Treatment Outcome
Anti-Bacterial Agents/therapeutic use
Synbiotics/administration & dosage

@article {pmid41078065,
year = {2025},
author = {Doukas, PG and Doukas, SG and Broder, A},
title = {Effectiveness and Safety of Fecal Microbiota Transplantation for Ulcerative Colitis Treatment: A Systematic Review and Meta-Analysis.},
journal = {Digestive diseases (Basel, Switzerland)},
volume = {},
number = {},
pages = {1-22},
doi = {10.1159/000548568},
pmid = {41078065},
issn = {1421-9875},
abstract = {Despite advances in pharmaceuticals, managing ulcerative colitis (UC) remains challenging. Interest in fecal microbiota transplantation (FMT) for UC is growing, but varying formulations and endpoints in trials complicate safety and efficacy assessment. This systematic review and meta-analysis offer a validated, up-to-date overview of FMT's efficacy and safety in UC. We searched four electronic databases and analyzed only randomized clinical trials (RCT) that investigated the clinical and endoscopic efficacy of FMT in UC, regardless of administration route or dose. Clinical and endoscopic remission was assessed by comparing the odds ratio (OR) and 95% confidence interval (CI). The initial search yielded 6737 studies with 15 meeting inclusion criteria after duplicate removal and screening. The meta-analysis showed clinical remission in 62% receiving FMT vs. 50.5% in controls (OR 2.65; [1.76; 4.00]). The endoscopic response was 42% in the FMT group vs. 22% in controls (OR 2.00; [1.09; 3.68]). Heterogeneity was assessed as low (by I2 index and τ2). Our data show that FMT significantly improves clinical and endoscopic remission rates, offering a promising non-pharmacological option for UC patients unresponsive to conventional treatments. Further prospective studies are needed to optimize the formulation and dosing while also addressing the safety profile of FMT in UC.},
}

@article {pmid41077748,
year = {2025},
author = {Lee, HK and Shin, CM and Chang, YH and Jo, H and Choi, J and Choi, Y and Jun, YK and Yoon, H and Park, YS and Kim, N and Lee, DH},
title = {Predictors of Treatment Response to Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Pilot Study.},
journal = {Journal of neurogastroenterology and motility},
volume = {31},
number = {4},
pages = {462-476},
doi = {10.5056/jnm24183},
pmid = {41077748},
issn = {2093-0879},
abstract = {BACKGROUND/AIMS: We aim to investigate the effectiveness, safety, and predictors of treatment response to fecal microbiota transplantation (FMT) in Korean irritable bowel syndrome (IBS) patients.

METHODS: Patients with moderate to severe diarrhea-predominant IBS (IBS-D) or mixed-type IBS (IBS-M) received FMT from one healthy donor via esophagogastroduodenoscopy. IBS-symptom severity score (IBS-SSS), Bristol stool form scale (BSFS), IBS Quality of Life (IBS-QoL) questionnaires, Hospital Anxiety and Depression Scale (HADS), and gut microbiome profiles were assessed at baseline, 4 weeks and 12 weeks post-FMT.

RESULTS: Among the 46 enrolled IBS patients, 37 patients (IBS-D:IBS-M = 28:9) completed a 12-week follow-up. Significant improvements were observed in IBS-SSS, IBS-QoL, and BSFS after 12 weeks. FMT led to increased microbial diversity and a sustained increase in beneficial bacterial genera, including Holdemanella, Ruminococcus, and Faecalibacterium. In terms of β-diversity, the distance between the patient's gut microbiome and that of the donor decreased after FMT; greater reduction in distance to donor microbiota was associated with greater symptom improvement (Unweighted UniFrac distance, P < 0.05). Responders (IBS-SSS reduction > 50 points) exhibited lower baseline relative abundances of Roseburia and Subdoligranulum, and more profound microbiome shifts toward the donor profile after FMT.

CONCLUSIONS: FMT appears to be a potentially effective treatment for moderate to severe IBS, with significant symptom relief and gut microbiota changes. Lower baseline abundances of Roseburia and Subdoligranulum and greater shifts of gut microbiome profile toward donor microbiota after FMT may predict favorable FMT response. Long-term follow-up is on the way to assessing the durability of these effects.},
}

@article {pmid41077742,
year = {2025},
author = {Gweon, TG},
title = {Is Fecal Microbiota Transplantation Applicable for the Treatment of Irritable Bowel Syndrome? Time for Precision Medicine.},
journal = {Journal of neurogastroenterology and motility},
volume = {31},
number = {4},
pages = {403-404},
doi = {10.5056/jnm25146},
pmid = {41077742},
issn = {2093-0879},
}

@article {pmid41077430,
year = {2025},
author = {Polster, SP},
title = {The Role of the Microbiome and the Neurovascular Unit.},
journal = {The Surgical clinics of North America},
volume = {105},
number = {5},
pages = {857-869},
doi = {10.1016/j.suc.2025.06.008},
pmid = {41077430},
issn = {1558-3171},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Blood-Brain Barrier ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {The gut-brain axis plays a crucial role in neurovascular diseases, linking gut microbiota to blood-brain barrier integrity, neuroinflammation, and disease progression. Conditions such as cerebral cavernous malformations, traumatic brain injury, radiation-induced damage, and stroke exhibit microbiome-driven modulation that may be relevant to explain disease variance. Microbial metabolites have been shown to influence endothelial function and secondary brain injury mechanisms. Emerging interventions of dietary modifications, probiotics, fecal microbiota transplantation, and metabolite-based therapies show promise in mitigating neurovascular damage. Future research should focus on microbiome-targeted treatments, biomarker discovery, and personalized strategies to optimize neurovascular health through gut microbiome modulation.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Blood-Brain Barrier
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid41076929,
year = {2025},
author = {Shi, W and Xi, M and Zhang, K and Yang, J and Cheng, X and Zang, H and Fan, W},
title = {Gut microbiota as a central mediator in hydrogen gas-induced alleviation of colitis via TLR4/NF-κB and Nrf2 pathway regulation.},
journal = {International immunopharmacology},
volume = {167},
number = {},
pages = {115671},
doi = {10.1016/j.intimp.2025.115671},
pmid = {41076929},
issn = {1878-1705},
abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing autoimmune disorder of the gastrointestinal tract with incompletely elucidated pathogenesis and limited therapeutic options. Although hydrogen gas (H2) has demonstrated therapeutic efficacy in various diseases including IBD, its mechanisms of action, particularly its interaction with the gut microbiota, remain poorly characterized. This study reveals that H2 inhalation effectively reversed dextran sulfate sodium (DSS)-induced dysbiosis by suppressing the expansion of potential pathogenic bacteria (e.g., Enterobacteriaceae and Escherichia-Shigella) and promoting potential beneficial microbes (e.g., Bacteroides and Lactobacillaceae), thereby restoring microbial homeostasis. Furthermore, H2 inhalation enhanced goblet cell density and mucus production, upregulated tight junction proteins (ZO-1 and occludin), and repaired intestinal barrier integrity. It also rebalanced the Treg/Th17 cell ratio, correcting immune dysregulation. At the molecular level, H2 inhalation suppressed the TLR4/NF-κB signaling pathway and activated the Keap1/Nrf2 antioxidant axis, leading to reduced production of pro-inflammatory cytokines and oxidative stress markers, alongside elevated antioxidant enzymes, collectively ameliorating colonic injury. In brief, the ameliorative effects of H2 are likely mediated through remodeling of the gut microbiota, restoration of the epithelial barrier, suppression of inflammatory signaling, and activation of antioxidant pathways. These findings were further validated by fecal microbiota transplantation (FMT) experiments. Collectively, this study links the therapeutic effects of H2 to structural and functional reprogramming of the gut microbiome, indicating that microbial ecological restoration is a central mechanism through which H2 alleviates colitis, thereby providing a mechanistic foundation for the therapeutic application of H2 inhalation in IBD.},
}

@article {pmid41076730,
year = {2025},
author = {Hull, MA and Sun, H},
title = {Omega-3 polyunsaturated fatty acids and gut microbiota.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
pmid = {41076730},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: Oral intake of n (omega)-3 polyunsaturated fatty acids (PUFAs) is associated with changes to gut microbiota. We review recent findings from 2024 onwards, which build the scientific case that changes to bacterial abundance, and their metabolites, contribute to the health benefits associated with n-3 PUFAs.

RECENT FINDINGS: There are now multiple studies in rodent disease models that demonstrate that n-3 PUFAs do not significantly alter bacterial diversity but, instead, alter abundance of several species that are implicated in short-chain fatty acid synthesis, in a model-specific manner. Limited intervention studies in humans, backed by larger observational studies, concur with the preclinical findings. Importantly, faecal transplantation experiments have confirmed that n-3 PUFA-induced changes to gut microbiota are causally related to reversal of the disease phenotype in two rodent models. In-vitro colonic models are now being used to understand the mechanism(s) underlying n-3 PUFA-induced changes to the gut microbiota and metabolome.

SUMMARY: Despite emerging proof that the gut microbiota contributes to n-3 PUFA activity in animal models, human data are sparse. It remains unclear how n-3 PUFAs affect changes to the gut microbiota or whether n-3 PUFA metabolism by gut microbes contributes to the host metabolome.},
}

@article {pmid41075966,
year = {2025},
author = {Wang, T and Huang, X and Lu, L and Luo, X and Wang, Y and Ma, Y and Tong, X and Zou, H and Gu, J and Liu, X and Bian, J and Liu, Z and Yuan, Y},
title = {The dysbiosis of gut microbiota attributes to the impairment of blood-brain barrier in rats triggered by cadmium.},
journal = {Toxicology},
volume = {},
number = {},
pages = {154303},
doi = {10.1016/j.tox.2025.154303},
pmid = {41075966},
issn = {1879-3185},
abstract = {Cadmium (Cd) is a non-biodegradable heavy metal with a long biological half-life that is detrimental to human health. As Cd can increase blood-brain barrier (BBB) permeability and disturb the gut microbiota, the relationship between the BBB and gut microbiota disturbance induced by Cd consumption remains unclear. This study aims to identify whether Cd-induced gut microbiota dysbiosis is associated with rat BBB injury and investigate the possible mechanism. Here, we conducted analyses of variations in the composition of the gut microbiota and its metabolites, as well as BBB permeability and the results of the Morris water maze test, in rats treated with Cd by gavage. Fecal microbiota transplantation was performed to verify the role of the microbiota in altering BBB permeability induced by Cd. The results showed that Cd disturbed the gut microbiota, decreasing the levels of short-chain fatty acids (SCFAs). Furthermore, Cd-induced BBB permeability was substantiated by FITC-dextran leakage, ultrastructural observations, and diminished Claudin-5, Occludin, and ZO-1 protein expression, all of which were mitigated by FMT. In vitro, sodium butyrate (SOB) alleviated Cd-induced oxidative stress and increased the expression levels of GPX4 and FTH. Taken together, these findings suggest that Cd disrupts the microbiota and SCFAs components in rats, thereby contributing to BBB damage. SOB prevents Cd-induced BBB damage by suppressing ferroptosis in microvascular endothelial cells. This exhaustive study considerably enhances our comprehension of the health hazards posed by Cd to the central nervous system via the gut-brain axis.},
}

@article {pmid41075893,
year = {2025},
author = {Huang, J and Yu, L and Zhang, C and Fang, Y and Zhou, X and Wang, R and Xing, L and Wang, L and Yu, N and Peng, D and Chen, W and Zhang, Y and Wang, Y},
title = {Water-soluble Poria cocos polysaccharide improves alcoholic liver disease via modulation of gut microbiota-mediated intestinal bile acids-farnesoid X receptor.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {148202},
doi = {10.1016/j.ijbiomac.2025.148202},
pmid = {41075893},
issn = {1879-0003},
abstract = {Alcoholic liver disease (ALD) is characterized by gut microbiota dysbiosis. This study aimed to elucidate the mechanism by which water-soluble Poria cocos polysaccharide (PCP) ameliorates ALD through modulation of the gut microbiota. PCP administration alleviated hepatic injury, reduced lipid accumulation, and attenuated inflammation in ALD mice. It also enhanced intestinal barrier integrity, as indicated by upregulation of tight junction proteins (ZO-1, Occludin, Claudin-1) and reduced lipopolysaccharide (LPS) levels. Additionally, PCP treatment remodeled the gut microbiota profile, characterized by a marked enrichment of Parabacteroides distasonis, which is associated with bile acid metabolism. Targeted metabolomics revealed PCP increased intestinal chenodeoxycholic acid (CDCA) and cholic acid (CA) levels, activating the intestinal farnesoid X receptor/fibroblast growth factor 15 (FXR/FGF15) axis while suppressing hepatic Cholesterol 7α-hydroxylase (CYP7A1), ultimately reducing systemic bile acids. Fecal microbiota transplantation confirmed gut microbiota-mediated protection, while intestinal FXR inhibition with glycine-β-muricholic acid (Gly-β-MCA) abolished PCP's therapeutic effects. These findings reveal that PCP ameliorates ALD by regulating the gut microbiota-bile acid-FXR axis, PCP as a promising natural therapeutic for ALD.},
}

@article {pmid41075520,
year = {2025},
author = {Gong, S and Xu, Y and Zhao, R and Yu, J and Bao, L and Zhang, Y and Li, F and Jiao, L and Kou, J},
title = {Xinqingning tablet attenuates ischemic stroke complicated by gut dysbiosis through regulating the miR-126-driven gut-brain axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157356},
doi = {10.1016/j.phymed.2025.157356},
pmid = {41075520},
issn = {1618-095X},
abstract = {BACKGROUND: Ischemic stroke (IS), the predominant clinical stroke subtype, is increasingly linked to dysregulation of the gut-brain axis (GBA)-a bidirectional neuroendocrine-immune interface connecting intestinal homeostasis with cerebrovascular pathophysiology. Xinqingning Tablet (XQNT) demonstrates neuroprotective potential in IS complicated by gut dysbiosis (GD), yet its mechanisms of GBA modulation remain unclear.

METHODS: A dual-hit IS-GD mouse model was established via fecal slurry transplantation and permanent middle cerebral artery occlusion (pMCAO) surgery. Gut function was evaluated by constipation indices and histopathological changes, while the neuroprotective efficacy of XQNT (0.36, 0.48, and 0.61 g kg⁻¹) was assessed via TTC staining, neurological deficit scores, cerebral water content, and Evans blue (EB) extravasation assays. Additionally, Western blot was employed to quantify blood-brain barrier (BBB) and inflammation-associated proteins. microRNA sequencing was used to screen the differentially expressed miRNAs. miR-126 expression levels were measured by RT-qPCR, while concentrations of LPS, IL-6 and IL-10 were determined by ELISA. Finally, mechanistic validation employed intravenous miR-126 agonism/antagonism coupled with phenotypic rescue experiments.

RESULTS: XQNT conferred robust survival benefits, while concurrently ameliorating intestinal dysfunction and neurovascular injury. Mechanistically, XQNT elevated miR-126 expression, suppressing NF-κB-driven neuroinflammation. Additionally, miR-126 agonism phenocopied XQNT efficacy, whereas miR-126 inhibition abrogated therapeutic benefits.

CONCLUSIONS: This study provides early evidence that XQNT functions as a dual-target GBA modulator that alleviates IS with GD via regulation of the miR-126/NF-κB axis. By simultaneously promoting barrier restoration and inflammatory resolution, XQNT offers a promising therapeutic approach that links regulation of the gastrointestinal system with cerebrovascular protection.},
}

@article {pmid41074196,
year = {2025},
author = {Liu, Y and Dong, B and Yang, YL and Zhang, YQ and Zhang, Y and Pan, D and Du, EZ and Zhu, SJ and Wang, B and Huang, YW},
title = {Intestinal microbiota dynamics in piglets: the interplay with swine enteric coronavirus infections and implications for disease control.},
journal = {Animal microbiome},
volume = {7},
number = {1},
pages = {107},
pmid = {41074196},
issn = {2524-4671},
support = {32302873//National Natural Science Foundation of China/ ; U22A20521//National Natural Science Foundation of China/ ; },
abstract = {Infections of swine enteric coronavirus (SECoV), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), cause severe diarrhea in piglets and result in substantial losses to the pig industry. The intestinal microbiota plays a crucial role in SECoV disease progression and outcomes, yet current research largely focuses on specific age groups or intestinal segments. This review provides a comprehensive analysis of the dynamic microbiota changes in piglets after SECoV infections across different ages and intestinal regions. It discusses differential microbiota analyses, functional changes, metabolic products, alongside their effects on immune responses. Additionally, we explore fecal bacterial transplantation as a potential intervention and highlight the role of the microbiota in either promoting or inhibiting SECoV infections. The development of advanced research tools, including culturomics, sequencing technologies, and multi-omics approaches, is pivotal in understanding the intricate relationship between the porcine intestinal microbiota and SECoV infections, offering potential strategies for preventing and controlling SECoV-related diseases.},
}

@article {pmid41072839,
year = {2025},
author = {Yu, G and Xie, W and Xiang, J and Ke, Y and Wang, Z and Tu, F and Wu, W and Hong, H and Lin, X},
title = {Gut microbiota remodelling alleviates elderly sepsis by microbiota-derived acetic acid via FFAR2/NLRP3 pathway.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178229},
doi = {10.1016/j.ejphar.2025.178229},
pmid = {41072839},
issn = {1879-0712},
abstract = {BACKGROUND: Elderly patients with sepsis have higher morbidity, mortality, and susceptibility than adults. Young-donor faecal microbiota transplantation (FMT) can remodel and improve intestinal dysbiosis to alleviate age-related diseases via microbiota-derived acetic acid and may be a treatment option for elderly sepsis. This study aimed to elucidate the influence of remodelling of the elderly gut microbiota on sepsis via acetic acid and explore the underlying mechanism. We analyzed the gut microbiota and plasma acetic acid in elderly patients with sepsis, performed young-donor FMT, and acetic acid supplementation in a caecum ligation and puncture-induced aged septic model mice, and assessed the effects of acetic acid on the septic myocardium by examining NLRP3 inflammasome in FFAR2 knockdown mice.

RESULTS: Elderly sepsis had higher mortality, reduced gut microbiota diversity, increased Escherichia-Shigella abundance, and reduced plasma acetic acid levels. Young-donor FMT improved the gut microbiota, increased the abundance of the probiotic genus Akkermansia and faecal acetic acid levels in the gut, and improved colon barrier function and outcomes. Intestinal acetic acid intervention improved age-related intestinal dysbiosis, organ dysfunction, and adverse effects in aged septic mice. These beneficial effects on the myocardium were mediated by activation of the FFAR2/NLRP3 axis, as evidenced by the finding that FFAR2 knockdown abrogated the amelioration of acetic acid. The elderly gut microbiota is fragile, which is related to the severity and poor prognosis of elderly sepsis.

CONCLUSION: Gut microbiota remodelling improves elderly sepsis via acetic acid, which can inhibit inflammatory reactions to alleviate myocardial damage by FFAR2/NLRP3 inflammasome inactivation.},
}

@article {pmid41072600,
year = {2025},
author = {Wang, Y and Wang, X and Gan, B and Jia, T and Xu, T and Xu, H},
title = {The "Butterfly Effect" of Heart Failure: Induced by the Combination of Polylactic Acid Nanoplastics and Copper from the Perspective of Gut Microbiome.},
journal = {Chemico-biological interactions},
volume = {},
number = {},
pages = {111769},
doi = {10.1016/j.cbi.2025.111769},
pmid = {41072600},
issn = {1872-7786},
abstract = {Plastic and heavy metal pollution have received extensive attention, but there is relatively little research on the damage to the gut-heart axis induced by the co-exposure to plastics and heavy metals. This study investigated the impact of the co-exposure of Polylactic acid nanoplastics (PLA-NPs) and copper (Cu) on heart failure (HF) in mice and explored the role of the gut microbiota in mediating this adverse outcome. Male C57BL/6J mice were divided into four groups: the Control group, the PLA-NPs group, the Cu group, and the Co-exposure group (PLA-NPs+Cu group). A 28-day exposure experiment was conducted. The research results indicate that, compared with the Single-exposure groups (PLA-NPs and Cu groups), the mice of Co-exposure group exhibited more severe toxic effects, including more pronounced myocardial hypertrophy and more severe myocardial fibrosis. These damages might be caused by increasing the heart's sensitivity to ferroptosis. Additionally, the co-exposure caused significant damage to the gut barrier and remarkable dysbiosis in the gut microbiota, such as a reduction in the abundances of beneficial bacteria like Lactobacillus. The fecal Microbiota Transplantation experiment confirmed that the alterations in gut microbiota play a pivotal role in the synergistic toxicity induced by PLA-NPs and Cu. This study for the first time reveals the mechanism of the combined effect of PLA-NPs and Cu on cardiac damage and emphasizes the crucial role of gut microbiota in this process.},
}

@article {pmid41071393,
year = {2025},
author = {Wasim, R},
title = {The gut immune axis in ulcerative colitis: insights from microbiome research.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {1006},
pmid = {41071393},
issn = {1573-4978},
mesh = {Humans ; *Colitis, Ulcerative/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; Dysbiosis/microbiology/immunology ; Probiotics/therapeutic use ; Intestinal Mucosa/immunology/microbiology ; Prebiotics ; Animals ; },
abstract = {Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease (IBD) marked by inflammation of the colonic mucosa. While its precise aetiology remains unclear, emerging evidence underscores the pivotal role of gut microbiota in UC pathogenesis. In healthy individuals, the gut microbiota contributes to immune modulation, nutrient absorption, and maintenance of intestinal barrier integrity. In contrast, individuals with UC exhibit gut dysbiosis-characterized by a reduction in beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium, and an increase in potentially pathogenic microbes like Escherichia coli. This microbial imbalance disrupts mucosal homeostasis, promotes persistent inflammation, and impairs epithelial healing. Contributing factors include genetic predisposition, antibiotic exposure, diet, and environmental influences. Novel microbiota-targeted interventions-such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT)-are being actively explored, with promising preliminary outcomes in symptom relief and microbiome restoration. However, challenges persist in defining a "healthy" microbiome and standardizing therapeutic protocols. This study highlights the potential of microbiome modulation as a transformative approach in UC management and calls for further research into host-microbe interactions to advance precision-based, microbiota-oriented therapies.},
}

Humans
*Colitis, Ulcerative/microbiology/immunology/therapy
*Gastrointestinal Microbiome/immunology
Fecal Microbiota Transplantation/methods
Dysbiosis/microbiology/immunology
Probiotics/therapeutic use
Intestinal Mucosa/immunology/microbiology
Prebiotics
Animals

@article {pmid41067318,
year = {2025},
author = {Zhao, H and Li, Y and Liu, N and Chen, P and Yu, X and Li, G and Deng, B and Li, D and Yang, F and Wang, G},
title = {Ganoderma lucidum polysaccharides alleviate non-alcoholic fatty liver disease by modulating gut microbiota against TLR4/NF-κB/MAPK pathway and activating AMPK pathway.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120723},
doi = {10.1016/j.jep.2025.120723},
pmid = {41067318},
issn = {1872-7573},
abstract = {Ganoderma lucidum (Leyss. ex Fr.) Karst has been a revered traditional Chinese medicinal herb, widely used in folk medicine to treat various metabolic diseases due to its remarkable bioactivities. Among its active components, G. lucidum polysaccharides are particularly recognized as one of the main contributors to its therapeutic effects. However, the therapeutic efficacy of G. lucidum polysaccharides against non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms remain to be elucidated.

AIMS OF THE STUDY: This study aimed to assess the therapeutic efficacy of a novel polysaccharide (EPGLa) derived from G. lucidum in the treatment of NAFLD and to elucidate its underlying mechanisms.

MATERIALS AND METHODS: The chemical characterization of the isolated and purified EPGLa was conducted using monosaccharide composition analysis, Fourier-transform infrared (FT-IR) spectroscopy, molecular weight determination, methylation analysis, and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Following the establishment of a NAFLD mouse model, the therapeutic effect of EPGLa on NAFLD was assessed, and its underlying mechanism was clarified.

RESULTS: The backbone of EPGLa consists of the following glycosidic linkages: →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →3,6)-β-D-Manp-(1→, →2)-α-D-Manp-(1→, and →4)-β-D-Galp-(1→. Its branches are composed of β-D-Glcp-(1→, β-D-Glcp-(1→3)-β-D-Glcp-(1→, and α-L-Fucp-(1→. In vivo results demonstrated that EPGLa effectively alleviated NAFLD by promoting the growth of beneficial gut bacteria to repair the intestinal barrier against Lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) pathways, and simultaneously enhancing short-chain fatty acid (SCFA) production to activate the AMP-activated protein kinase (AMPK) pathway. To further validate these findings, we employed fecal microbiota transplantation (FMT), which confirmed the role of EPGLa in modulating gut microbiota against NAFLD.

CONCLUSION: Our study provides compelling evidence that EPGLa holds promise as a potential therapeutic agent for the intervention of NAFLD, and our findings also offer novel insights into the therapeutic targets of other bioactive polysaccharides.},
}

@article {pmid41067200,
year = {2025},
author = {Ding, L and Li, Q and Qi, K and Chen, Y and Hu, N and Hu, S and Fang, T and Guan, S and Wang, J and Qiu, J and Deng, X and Xu, L},
title = {Phloretin alleviates Salmonella pullorum infection by modulating gut microbiota-derived 3-phenylpropionic acid and AhR/IL-22/STAT-3 axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157350},
doi = {10.1016/j.phymed.2025.157350},
pmid = {41067200},
issn = {1618-095X},
abstract = {BACKGROUND: Salmonella pullorum (S. pullorum) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate gut microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated.

PURPOSE: This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks.

METHODS: H&E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum-infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection.

RESULTS: Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum-infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium, and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum-induced intestinal barrier damage and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis.

CONCLUSION: These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum-infected chicks.},
}

@article {pmid41066868,
year = {2025},
author = {Zeng, Z and Li, H and Yang, W and Li, L and Ni, P and Chen, Q and Zhou, W and Peng, J and Huang, L},
title = {Probiotic VSL#3 alleviates intrahepatic cholestasis of pregnancy by upregulating farnesoid X receptor-fibroblast growth factor 15 through regulation of the gut microbiota.},
journal = {Journal of reproductive immunology},
volume = {172},
number = {},
pages = {104653},
doi = {10.1016/j.jri.2025.104653},
pmid = {41066868},
issn = {1872-7603},
abstract = {Intrahepatic cholestasis of pregnancy (ICP) poses significant risks to both maternal and fetal health, and treatment options remain limited. This study investigated the efficacy and underlying mechanisms of VSL#3 in alleviating ICP. Clinical fecal and blood samples were collected from 26 patients with ICP and 21 healthy pregnant women. The gut microbiota composition was analyzed using 16S rRNA sequencing. To further explore causality, we established a fecal microbiota transplantation-ICP mouse model using fecal samples from ICP patients, as well as an estrogen-induced ICP mouse model. Compared with healthy pregnant women, ICP patients exhibited a distinct gut microbiota profile, characterized by an increased abundance of Bacteroides and Alistipes. Serum FGF19 levels were significantly lower in ICP patients, showing a negative correlation with liver function markers, such as serum total bile acid (TBA), and a positive correlation with beneficial genera including Bifidobacterium, Ruminococcus, Blautia, Dorea, Eubacterium (hallii group) and Ruminococcus (torques group). VSL#3 treatment in mice alleviated ICP manifestations by improving liver histopathology, reducing TBA and alanine aminotransferase levels, increasing FGF15 concentrations, and enhancing fetal outcomes. These beneficial effects were abolished by co-administration of the FXR antagonist Z-guggulsterone, confirming the role of FXR signaling. In conclusion, VSL#3 alleviated ICP by modulating the gut microbiota to activate the FXR-FGF15 axis, thereby reducing bile acid synthesis and improving maternal and fetal outcomes.},
}

@article {pmid41065216,
year = {2025},
author = {Heer, P and Fernandez Elviro, C and Koutsokera, A and Mornand, A and Rochat, I and Regamey, N and Blanchon, S},
title = {Identification of early changes in multiple biomarkers following CFTR modulator initiation in patients with cystic fibrosis.},
journal = {Therapeutic advances in respiratory disease},
volume = {19},
number = {},
pages = {17534666251376211},
doi = {10.1177/17534666251376211},
pmid = {41065216},
issn = {1753-4666},
mesh = {Humans ; *Cystic Fibrosis/drug therapy/physiopathology/diagnosis/genetics/metabolism ; *Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism/drug effects ; Male ; Female ; *Aminophenols/therapeutic use/adverse effects ; *Benzodioxoles/therapeutic use/adverse effects ; *Quinolones/therapeutic use/adverse effects ; Prospective Studies ; Child ; Biomarkers/metabolism/blood ; Adolescent ; Treatment Outcome ; *Aminopyridines/therapeutic use ; Time Factors ; *Indoles/therapeutic use/adverse effects ; *Chloride Channel Agonists/therapeutic use/adverse effects ; Drug Combinations ; Young Adult ; *Pyrazoles/therapeutic use ; Sweat/chemistry ; Adult ; Pyrrolidines/therapeutic use ; },
abstract = {BACKGROUND: There are currently no early parameters that allow prediction of long-term responses to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator treatment on an individual level.

OBJECTIVES: To identify early parameters measured within 7 to 14 days after initiation of treatment with a CFTR modulator to assess CFTR modulator efficacy.

STUDY DESIGN: Prospective observational study of patients diagnosed with CF who begin elexacaftor/tezacaftor/ivacaftor (ETI) therapy at 3 CF clinics in Switzerland (Geneva, Lausanne, Lucerne).

METHODS: Standardized measurements were taken within 2 months prior to and 7 to 14 days after starting CFTR modulator treatment.

RESULTS: ETI treatment was started on 47 patients [median age: 12 years] of whom 12 (26%) were switching from lumacaftor/ivacaftor (n = 8) or tezacaftor/ivacaftor (n = 4) to ETI. A significant early treatment effect was observed for BMI z-score (p < 0.001) and inflammatory parameters (white blood cells (p = 0.006), neutrophils (p = 0.006), immunoglobulin G (p = 0.012), and fecal calprotectin (p = 0.002)). In CFTR functional assays, sweat chloride concentration and nasal potential difference testing [Δlow-chloride+isoproterenol, Sermet score, and Wilschanski index] improved significantly (all p < 0.001). Improvement was also observed in lung function (FVC, FEV1, MMEF25-75, LCI2.5%) (all p < 0.001). No changes were found for blood pressure, SpO2, respiratory rate, erythrocyte sedimentation rate, C-reactive protein, and fecal elastase.

CONCLUSION: This study identified clinical, biologic, and functional parameters showing treatment effect early after initiation of CFTR modulator therapy. These parameters may serve as potential predictors of long-term responses to CFTR modulator treatment.},
}

Humans
*Cystic Fibrosis/drug therapy/physiopathology/diagnosis/genetics/metabolism
*Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism/drug effects
Male
Female
*Aminophenols/therapeutic use/adverse effects
*Benzodioxoles/therapeutic use/adverse effects
*Quinolones/therapeutic use/adverse effects
Prospective Studies
Child
Biomarkers/metabolism/blood
Adolescent
Treatment Outcome
*Aminopyridines/therapeutic use
Time Factors
*Indoles/therapeutic use/adverse effects
*Chloride Channel Agonists/therapeutic use/adverse effects
Drug Combinations
Young Adult
*Pyrazoles/therapeutic use
Sweat/chemistry
Adult
Pyrrolidines/therapeutic use

@article {pmid41064515,
year = {2025},
author = {Aumpan, N and Chonprasertsuk, S and Pornthisarn, B and Siramolpiwat, S and Bhanthumkomol, P and Issariyakulkarn, N and Gamnarai, P and Bongkotvirawan, P and Wongcha-Um, A and Mahachai, V and Vilaichone, RK},
title = {Efficacy of encapsulated fecal microbiota transplantation and FMT via rectal enema for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial (CAP-ENEMA FMT Trial).},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1648944},
pmid = {41064515},
issn = {2296-858X},
abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) is a functional bowel disorder. Gut dysbiosis involves in pathogenesis of IBS. Limited studies compared efficacy of fecal microbiota transplantation (FMT) via different routes of administration. This study aimed to compare efficacy of encapsulated FMT, FMT via rectal enema, and placebo in IBS patients.

METHODS: In this double-blind, randomized, placebo-controlled study, we enrolled patients aged 18-70 years with IBS defined by Rome IV criteria at Thammasat university, Thailand. Patients were randomized into three groups: (1) encapsulated FMT (six capsules twice daily for two consecutive days, total 50 g of stool), (2) FMT via rectal enema (50 g of stool in 200 mL of isotonic saline), or (3) placebo. Primary endpoint was clinical response defined by ≥50-point decrease in IBS-symptom severity score (IBS-SSS) at 4 weeks. Secondary outcomes were quality of life and changes of fecal microbiota composition after treatment. The study was registered with ClinicalTrials.gov, number NCT06201182.

RESULTS: From August 20, 2020, to February 15, 2024, 45 patients were randomized to receive encapsulated FMT (n = 15), FMT via rectal enema (n = 15), or placebo (n = 15). There was no difference in patient characteristics and baseline IBS-SSS between groups. Encapsulated FMT provided significantly improved IBS-SSS (166.7 ± 73.7 vs. 269.3 ± 69.5, p = 0.001), clinical response (86.7 vs. 26.7%, p = 0.001), and quality of life (31.7 ± 4.8 vs. 25.1 ± 5.2, p < 0.001) at 4 weeks compared with placebo. FMT via rectal enema demonstrated better IBS-SSS (168.7 ± 101.9 vs. 269.3 ± 69.5, p = 0.004), clinical response (73.3 vs. 26.7%, p = 0.011), and quality of life (30.2 ± 5.0 vs. 21.0 ± 7.4, p < 0.001) than placebo. Clinical response and quality of life between encapsulated FMT and FMT via rectal enema were not different. No serious adverse event was observed. Minor adverse events such as bloating and diarrhea were not different between all groups.

CONCLUSIONS: Higher clinical response and quality of life were demonstrated in both FMT groups than placebo. Either encapsulated FMT or FMT via rectal enema was safe and could provide favorable outcomes for IBS patients.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06201182, Identifier: NCT06201182.},
}

@article {pmid41063317,
year = {2025},
author = {Gong, K and Zhang, S and Pan, Y and Cai, Q and Wu, M and Yin, X and Ma, J and Ji, H and Wang, Z and Wu, W and Zheng, H},
title = {Alternate day fasting alleviates neuroinflammation in diabetic mice by regulating δ-valerobetaine-carnitine-microglia axis via enrichment of Akkermansia muciniphila.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {202},
pmid = {41063317},
issn = {2049-2618},
support = {22074106//National Natural Science Foundation of China/ ; LY23H090008//Zhejiang Provincial Natural Science Foundation of China/ ; },
mesh = {Animals ; Mice ; *Carnitine/metabolism ; Gastrointestinal Microbiome/physiology ; *Fasting ; *Microglia/metabolism ; Akkermansia ; *Neuroinflammatory Diseases/metabolism ; *Diabetes Mellitus, Type 1/microbiology/metabolism ; *Verrucomicrobia ; Mice, Inbred C57BL ; *Diabetes Mellitus, Experimental/microbiology ; Male ; *Betaine/metabolism/analogs & derivatives ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND: Alternate day fasting (ADF) as a healthy dietary pattern has been reported to improve brain functions and behaviors, but the effect of ADF on diabetes-related brain disorders and the potential mechanisms remain unclear. In this study, we investigated the impact of ADF on neuroinflammation and exploratory behavior in type 1 diabetic (T1D) mice and explored the specific molecular mechanisms from the perspective of the gut microbiota and host metabolism.

RESULTS: ADF can effectively relieve neuroinflammation and exploratory behavioral disorders in T1D mice. According to fecal microbiota transplant and bacterial supplementation, we demonstrated that ADF-driven enrichment of Akkermansia muciniphila (AKK) was necessary for boosting exploratory behavior in T1D mice. The gut microbiota-derived metabolite δ-valerobetaine (VB) reduced hepatic carnitine synthesis by inhibiting BBOX, and caused exploratory behavioral disorders in mice. In vitro and in vivo studies revealed that AKK bacteria had the ability to consume VB, and thereby increased systemic carnitine level. In addition, carnitine was found to deplete lipid droplet accumulation in microglia by enhancing fatty acid oxidation and lipolysis, reduce neuroinflammation and neuron injury, and then increase exploratory behavior in T1D mice.

CONCLUSIONS: Our study sheds light on the gut-liver-brain metabolic axis mechanism on the protective role of ADF in T1D-associated neuroinflammation and exploratory behavioral disorders and AKK bacteria exert as a key mediator. Video Abstract.},
}

Animals
Mice
*Carnitine/metabolism
Gastrointestinal Microbiome/physiology
*Fasting
*Microglia/metabolism
Akkermansia
*Neuroinflammatory Diseases/metabolism
*Diabetes Mellitus, Type 1/microbiology/metabolism
*Verrucomicrobia
Mice, Inbred C57BL
*Diabetes Mellitus, Experimental/microbiology
Male
*Betaine/metabolism/analogs & derivatives
Fecal Microbiota Transplantation

@article {pmid41061446,
year = {2025},
author = {Zhang, J and Lv, Y and Yang, S and Li, H and Luo, Y and Tang, X and Xu, J and Liu, X},
title = {Deciphering the regulatory role of selenium on cadmium bioavailability and toxicity: From the perspective of gut microbiota.},
journal = {Ecotoxicology and environmental safety},
volume = {305},
number = {},
pages = {119193},
doi = {10.1016/j.ecoenv.2025.119193},
pmid = {41061446},
issn = {1090-2414},
abstract = {Residents in areas naturally rich in cadmium (Cd) and selenium (Se) frequently exhibit exceptional longevity, raising intriguing questions about the interplay between the two elements. However, whether co-exposure affects the bioavailability of Cd remains unclear. Meanwhile, it is necessary to unclose the antagonistic mechanisms between Se and Cd. Here, a mouse bioassay was conducted to assess the impact of Se addition at low (0.1 mg/kg), medium (0.5 mg/kg) and high (2 mg/kg) doses, and duration (10 and 30 d) on Cd bioavailability of rice and Cd-induced hepatic toxicity. Results showed that Se cannot reduce Cd bioavailability. Medium Se addition for a duration of 10 days (MSe10) exhibited the highest efficacy in attenuating hepatic inflammation, as evidenced by augmented antioxidant enzyme activity, alleviated pathological damage, and increased levels of anti-inflammatory metabolites within the liver. The benefit was associated with its restoration of the gut microbiota and changes in key metabolic pathways. Notably, MSe10 increased the abundance of Faecalibaculum and Dubosiella, and enhanced the levels of secondary bile acids. Neither 0.1 mg/kg, 2 mg/kg nor long time addition of Se was beneficial for liver recovery. The hepatic lesions were fecal microbiota-dependent, as supported by fecal microbiota transplantation. Microbiota from MSe10 were capable to ameliorate hepatic inflammation, strengthen the intestinal barrier, and inhibit lipopolysaccharides (LPS) accumulation in blood. Additionally, the study provided insights into Se as an intervention for Cd toxicity, highlighting the appropriate dosage and its potential to reduce health risks.},
}

@article {pmid41061376,
year = {2025},
author = {Wekking, D and Ende, TVD and Bijlsma, MF and Vidal-Itriago, A and Nieuwdorp, M and van Laarhoven, HWM},
title = {Fecal microbiota transplantation to enhance cancer treatment outcomes across different cancer types: A systematic literature review.},
journal = {Cancer treatment reviews},
volume = {140},
number = {},
pages = {103025},
doi = {10.1016/j.ctrv.2025.103025},
pmid = {41061376},
issn = {1532-1967},
abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action.

METHODS: A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen.

RESULTS: 45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration.

CONCLUSION: Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.},
}

@article {pmid41059058,
year = {2025},
author = {Wang, Y and Bai, Z and Liu, Y and Wang, Y and Xu, J and Lai, Z},
title = {Influence of the gut microbiota on the pharmacokinetics of tacrolimus in liver transplant recipients: insights from microbiome analysis.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1616985},
pmid = {41059058},
issn = {1664-302X},
abstract = {INTRODUCTION: Tacrolimus is crucial for immunosuppression after liver transplantation, but its pharmacokinetics vary markedly among individuals. Emerging evidence suggests that the gut microbiota may influence its metabolism, although the underlying mechanisms remain unclear.

METHODS: This study analyzed the fecal microbiota from 38 postliver transplant patients and 31 healthy controls via 16S rDNA amplicon and shotgun metagenomic sequencing. Patients were stratified into three groups on the basis of oral tacrolimus dosage and blood concentration: LDLBC (low dose, low blood concentration), LDHBC (low dose, high blood concentration), and SDLBC (standard dose, low blood concentration).

RESULTS: Posttransplant patients presented significantly reduced gut microbial diversity. Specific bacterial taxa, including Enterococcus raffinosus, Intestinibacter bartlettii, and Bacteroides fragilis, were enriched in patients with lower tacrolimus blood concentrations. In contrast, Phascolarctobacterium faecium and Streptococcus salivarius were associated with increased drug levels. Functional analysis revealed differences between patient subgroups in ATP-binding cassette (ABC) transporters and drug efflux pumps, suggesting a potential microbial influence on tacrolimus absorption and metabolism. Additionally, antibiotic resistance genes were more abundant in patients with lower tacrolimus blood concentrations, particularly in the Escherichia coli-enriched groups.

DISCUSSION: These findings underscore the influence of the gut microbiota on tacrolimus pharmacokinetics and support the potential of microbial composition as a biomarker for optimizing immunosuppressive therapy.},
}

@article {pmid41057955,
year = {2025},
author = {Chen, W and Liu, C and Li, X and Yang, X and Liu, Y and Qin, M and Jiang, W and Wang, Y and Sun, H and Li, G and Wen, B and He, S},
title = {5,7-dimethoxyflavone inhibits hepatocellular carcinoma progression via increasing intestinal Akkermansia muciniphila and hepatic CD8[+] T cell infiltration.},
journal = {Chinese medicine},
volume = {20},
number = {1},
pages = {170},
pmid = {41057955},
issn = {1749-8546},
support = {82405072//National Natural Science Foundation of China/ ; 82304927//National Natural Science Foundation of China/ ; 82274286//National Natural Science Foundation of China/ ; 2023A1515110041//Joint Funds of Basic and Applied Basic Research Fund of Guangdong/ ; 2023M741596//China Postdoctoral Science Foundation/ ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) mainly develops in cases of fibrosis and cirrhosis and is accompanied by intestinal flora disorder. HCC also affects CD8[+] T cell immune function. 5,7-Dimethoxyflavone (DMF), an active flavonoid with anti-tumor effect, is found in Kaempferia parviflora. However, whether DMF can treat HCC remains unclear. This study aims to investigate the effect of DMF on HCC and to explore its possible mechanism, focusing on the gut microbiota regulation and the effect of CD8[+] T cells in a murine model.

METHODS: The HCC mouse model was induced with diethylnitrosamine/carbon tetrachloride and orally administered DMF. DMF effects on HCC progression were assessed using hematoxylin and eosin staining, immunohistochemistry, and serum biochemical marker levels. The causal relationship between gut microbes and HCC was explored using 16S rRNA genome-derived taxonomic profiling, microbial transplantation, fecal high-throughput targeted metabolomics, and untargeted serum metabolomic analyses. Transcriptome analysis, molecular docking, quantitative real-time polymerase chain reaction, and Western blot were applied to study the genes targeted by DMF. CD8[+] T cell infiltration and tumor-killing factors were studied using flow cytometry and immunofluorescence staining.

RESULTS: DMF reduced the number of tumors, the largest tumor size, and the liver-to-body ratio while also improving liver function. An antibiotic cocktail lowered the anti-tumor effect of DMF, indicating that DMF inhibition of HCC is partially dependent on the gut microbiota. DMF considerably upregulates Akkermansia muciniphila during chemical hepatocarcinogenesis in mice. DMF-upregulated A. muciniphila leading to intestinal barrier repair, which inhibited HCC progression by enhancing antioxidant capacity through glutathione regulation and 11,12-DIHETrE down-regulation. An untargeted serum metabolomic analysis showed that there existed additional mechanisms underlying DMF anti-tumor effect following its absorption into the bloodstream. DMF enhances the infiltration effect of CD8[+] T cells and upregulates interferon-gamma expression in HCC tissue. Overall, 822 genes, including chemokine (C-C motif) ligand 2 (CCL2), were significantly downregulated by DMF treatment in HCC cells. Notably, DMF binds strongly with nuclear factor kappa-B (NF-κB) and inhibits NF-κB p65 phosphorylation, sequentially suppressing the expression of downstream protein CCL2, which mediate the crosstalk between tumor cells and CD8[+] T cells.

CONCLUSION: DMF improves A. muciniphila-mediated intestinal barrier repair and inhibits the NF-κB/CCL2 pathway in HCC cells, enhancing the immunity of CD8[+] T cells in the liver. Hence, it may serve as a potential candidate for HCC treatment.},
}

@article {pmid41055380,
year = {2025},
author = {Du, J-Y and Zhang, Z-J and Tan, L and Yang, J-Y and Yang, R-N and Chen, Y-L and Tan, G-F and Li, J and Li, W-J and Yang, L and Cai, J and Shen, D-L and Zhu, H-R and Fan, Z-X and Yuan, M-L and Zhang, W},
title = {Gut microbiota dysbiosis and metabolic perturbations of bile/glyceric acids in major depressive disorder with IBS comorbidity.},
journal = {mBio},
volume = {},
number = {},
pages = {e0244725},
doi = {10.1128/mbio.02447-25},
pmid = {41055380},
issn = {2150-7511},
abstract = {Major depressive disorder (MDD) and irritable bowel syndrome (IBS) exhibit high comorbidity, yet their shared pathophysiology remains unclear. Previous studies have primarily focused on the psychological health in the IBS population, without considering psychiatric diagnoses or stratifying different psychological states, potentially leading to biased findings. This study employed multi-omics approaches to characterize gut microbiota and serum metabolites in 120 MDD patients (47 with IBS and 73 without IBS) and 70 healthy controls (HCs). MDD with IBS patients showed significantly higher depression (Hamilton depression scale [HAMD-17]) and anxiety (Hamilton anxiety scale [HAMA-14]) scores than MDD-only patients (P < 0.05). Metagenomic sequencing of fecal samples revealed increased alpha diversity (Chao1/Shannon indices) and Firmicutes dominance in both MDD groups vs HC, while Actinobacteria enrichment specifically marked MDD with IBS. Functionally, MDD with IBS uniquely activated D-amino acid/glycerolipid metabolism pathways (Kyoto Encyclopedia of Genes and Genomes). Serum metabolomics identified comorbid-specific perturbations: downregulation of bile acids (CDCA, GCDCA, GCDCA-3S) and upregulation of glyceric acid/glutaconic acid. Our study also found that Eggerthella lenta and Clostridium scindens are differentially abundant bacteria that are involved in bile acid metabolism, and that microbial genes (e.g., K03738) are associated with glyceric acid production. These findings implicate gut microbiota-driven bile acid/glyceric acid dysregulation in MDD with IBS comorbidity, supporting the gut-brain axis as a therapeutic target for probiotics or microbiota transplantation.IMPORTANCEMajor depressive disorder (MDD) exhibits a high comorbidity rate with irritable bowel syndrome (IBS). Our study, conducted on 120 MDD patients (47 of whom were comorbid with IBS) and a control group of 70 individuals, revealed that MDD-IBS comorbid patients demonstrated significantly higher depression/anxiety scores. Multi-omics analysis indicated substantial alterations in the gut microbiota (e.g., Firmicutes, Actinobacteria) and serum metabolites (e.g., bile acids, glyceric acid) among MDD-IBS patients, which were associated with specific metabolic pathways. Therefore, the new aspect of this study was the inclusion of patients with MDD but without IBS symptoms, which provided a deeper understanding of the intestinal microbiota dysregulation associated with comorbid IBS and MDD. These findings suggest that there may be involvement of the gut-brain axis, providing new research directions for potential therapeutic targets.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2100041598.},
}

@article {pmid41052982,
year = {2025},
author = {Cao, Y and Fan, X and Zang, T and Qiu, T and Fang, Q and Bai, J and Liu, Y},
title = {Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {383},
pmid = {41052982},
issn = {2158-3188},
support = {2023AFB710//Natural Science Foundation of Hebei Province (Hebei Provincial Natural Science Foundation)/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; *Hippocampus/metabolism/pathology/immunology ; Mice ; Pregnancy ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; *Dysbiosis/microbiology/complications ; Humans ; Lipopolysaccharides/blood ; Germ-Free Life ; *Neuroinflammatory Diseases/metabolism/microbiology ; Microglia ; *Pregnancy Complications/microbiology ; Disease Models, Animal ; Behavior, Animal ; Interleukin-6/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {Numerous studies have described the role of the microbiome-gut-brain axis in depression. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of prenatal depression are limited. In this study, fecal microbiota from women with prenatal depression was transplanted into germ-free mice to investigate the potential causal relationships between the gut microbiota and depressive phenotypes. Shotgun metagenomic sequencing and untargeted metabolomics approaches were used to investigate the characteristics of gut microbiota and microbial metabolites. The levels of neuroinflammation in the brain were detected using immunofluorescence and real-time quantitative PCR. We found significant changes in gut microbiota composition and metabolites in mice with fecal microbiota transplantation (FMT) from women with prenatal depression, including decreased Ligilactobacillus, increased Akkermansia, and abnormal glycerophospholipid metabolism. Besides, significant increase in plasma lipopolysaccharide (LPS) levels and significant proliferation of microglia in the hippocampus were observed in mice receiving FMT from women with prenatal depression, accompanied by a significant increase in the expression of nuclear factor-κB (NF-κB) p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA. The gut microbiota and its metabolites were strongly associated with depressive-like behaviors, plasma LPS and neuroinflammation. Our study collectively demonstrates that dysbiosis of the gut microbiota may play a causal relationship in the development of prenatal depression. This process potentially involves the activation of neuroinflammation through the LPS-NF-κB signaling pathway.},
}

Animals
*Gastrointestinal Microbiome/physiology
Female
*Hippocampus/metabolism/pathology/immunology
Mice
Pregnancy
Fecal Microbiota Transplantation
*Depression/microbiology/metabolism
*Dysbiosis/microbiology/complications
Humans
Lipopolysaccharides/blood
Germ-Free Life
*Neuroinflammatory Diseases/metabolism/microbiology
Microglia
*Pregnancy Complications/microbiology
Disease Models, Animal
Behavior, Animal
Interleukin-6/metabolism
Tumor Necrosis Factor-alpha/metabolism

@article {pmid41052746,
year = {2025},
author = {Chen, Y and Yu, L and Zhang, L and Liu, C and You, Y and Guo, H and Li, Z and Yin, X and Hong, T and Ding, L and Fang, Q},
title = {Gut microbiota dysbiosis exacerbates post-stroke depression via microglial NLRP3 inflammasome activation.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115488},
doi = {10.1016/j.expneurol.2025.115488},
pmid = {41052746},
issn = {1090-2430},
abstract = {BACKGROUND: Post-stroke depression (PSD) is a neuropsychiatric complication prevalent among stroke survivors. Emerging evidence suggests that dysregulation of the microbiota-gut-brain axis is implicated in the pathogenesis of PSD. However, the exact mechanism is not clear and further research is necessary.

METHODS: Initially, Sprague-Dawley (SD) rats were randomly allocated into three experimental groups: Sham, Middle Cerebral Artery Occlusion (MCAO), and PSD. Behavioral tests were conducted to evaluate depressive-like behavior. Fecal samples from all groups underwent 16S rRNA sequencing for comprehensive gut microbiota analysis. Colonic tissues were collected from rats and subjected to immunohistochemical analysis for quantification of tight junction proteins (ZO-1, Occludin, and Claudin). Peripheral blood plasma was obtained for the determination of IL-1β, IL-6, TNF-α, and IL-18 levels using enzyme-linked immunosorbent assay (ELISA). Lastly, hippocampus tissues were harvested for molecular characterization of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and inflammatory cytokines expression through tripartite methodology: Reverse Transcription quantitative PCR (RT-qPCR), Western blot, and immunofluorescence. Concurrently, hippocampal concentrations of 5-HT, BDNF, and PSD-95 were also measured by ELISA. Subsequently, Fecal Microbiota Transplantation (FMT) was performed by administering fecal suspensions from PSD and Sham donor rats to healthy SD recipients via oral gavage. Then, use the above methods to test the same indicator.

RESULT: Comparative analyses showed that microbial species richness and diversity indices were significantly reduced in PSD model rats, along with a compositional imbalance of the gut microbiota. Concurrently, reduced expression of the colonic tight junction proteins ZO-1, Occludin, and Claudin was observed, accompanied by elevated levels of peripheral inflammatory cytokines. In PSD rats, NLRP3 inflammasome activation was detected in the ischemic hippocampus, along with increased expression of the inflammatory cytokines IL-18 and IL-1β, and decreased levels of 5-HT, BDNF, and PSD-95. Subsequently, using FMT technology, PSD rat feces were innovatively prepared into a fecal suspension and administered to healthy SD rats. Analysis revealed that FMT-PSD rats exhibited a disrupted gut microbiota structure, impaired colonic barrier integrity, activation of the hippocampal NLRP3 inflammasome, elevated inflammatory cytokine levels, and reduced neurotransmitter expression.

CONCLUSION: In summary, these data demonstrate that dysbiosis of the intestinal microbiota compromises gut barrier integrity and elicits systemic inflammation, which may subsequently activate the NLRP3 inflammasome in hippocampal microglia. This activation promotes the release of pro-inflammatory cytokines IL-18 and IL-1β, and coincides with dysregulation of emotion-related neurotransmitters, collectively contributing to the pathogenesis of PSD.},
}

@article {pmid41052446,
year = {2025},
author = {Sacks, HS and , },
title = {In primary CDI, fecal microbiota transplantation was noninferior to vancomycin for clinical cure at 14 d without recurrence at 60 d.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-25-03648-JC},
pmid = {41052446},
issn = {1539-3704},
abstract = {GIM/FP/GP: [Formula: see text] Gastroenterology: [Formula: see text] Infectious Disease: [Formula: see text].},
}

@article {pmid41048505,
year = {2025},
author = {Yang, W and Jin, Q and Xiao, D and Li, X and Huang, D},
title = {Interaction mechanism and intervention strategy between metabolic dysfunction-associated steatotic liver disease and intestinal microbiota.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1597995},
pmid = {41048505},
issn = {1664-302X},
abstract = {The interaction between metabolic dysfunction-associated seatotic liver disease (MASLD) and gut microbiota regulates hepatic metabolic homeostasis through the gut-liver axis, and its mechanisms involve intestinal dysbiosis (decreased bacteroidetes, increased ratio of firmicutes/proteobacteria), bile acid metabolism reprogramming (secondary bile acids inhibit FXR signaling), short-chain fatty acid (SCFAs) deficiency, and endotoxin-mediated inflammatory activation (TLR4/NF-κB pathway). Among the intervention strategies, probiotics (such as Bifidobacteria) improved inflammation by regulating microbiota structure and intestinal barrier function, prebiotics such as resistant starch enriched butyric acid-producing bacteria and reduced liver lipid deposition, fecal microbiota transplantation (FMT) could remodel the microbiota but needed to optimize safety, restricted fructose intake and Mediterranean diet reduced liver damage by regulating microbiota metabolism, and metabolic surgery improved fibrosis through microbiota remodeling and bile acid signaling. In the future, it is necessary to combine multi-omics technology to analyze the microbiota-host interaction network, develop precision therapies such as phage targeted clearance or engineering bacterial delivery of metabolites, and promote the clinical transformation of personalized intervention programs.},
}

@article {pmid41047993,
year = {2025},
author = {Paaske, SE and Baunwall, SMD and Rubak, T and Rågård, N and Kelsen, J and Hansen, MM and Lødrup, AB and Lyhne, S and Glavind, E and Fernis, CMC and Hald, S and Erikstrup, LT and Vinter-Jensen, L and Lal, S and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL},
title = {Improving Clinical Outcomes of Encapsulated Faecal Microbiota Transplantation for Clostridioides difficile Infection Through Empirical Donor Selection and Optimised Dosing: A Quality Improvement Study.},
journal = {Alimentary pharmacology & therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1111/apt.70395},
pmid = {41047993},
issn = {1365-2036},
support = {8056-00006B//Innovationsfonden/ ; },
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for Clostridioides difficile infection (CDI), but real-world effectiveness data are warranted to refine treatment algorithms. We previously found that FMT effectiveness varied with donors, and the effect of a single capsule FMT administration was lower than expected.

AIMS: To improve FMT outcomes through empirical donor exclusion and application of an optimised capsule FMT dosing regimen.

METHODS: In this multi-site Danish quality improvement study, we included patients with CDI treated with capsule-based FMT from 24 June 2019 to 30 September 2024. The primary outcome was cure of C. difficile-associated diarrhoea (CDAD) 8 weeks after FMT. We assessed this using statistical process control charts monitored separately for the primary FMT centre and the external FMT sites. We used multivariable, mixed-effect logistic regression analysis to evaluate the impact of FMT dosing while adjusting for patient, donor and CDI-related factors.

RESULTS: We included 1176 patients (1707 FMT treatments). At external FMT sites, the cure rate from one FMT treatment changed from 50% (95% confidence interval (CI): 45%-56%) to 59% (55%-63%) following the exclusion of three low-performing donors in November 2022. After implementing a two-dose capsule FMT dosing regimen in February 2024, the cure rate increased to 72% (65%-77%). The impact of the two-dose capsule FMT dosing regimen remained statistically significant after adjustment (odds ratio 1.22; 95% CI 1.16-1.28; p < 0.001).

CONCLUSION: Empirical donor selection and a two-dose capsule FMT regimen improved clinical outcomes in a large-scale system treating patients with CDI.},
}

@article {pmid41047724,
year = {2025},
author = {de Groen, P and Fuhri Snethlage, CM and Wortelboer, K and Tokgöz, S and Davids, M and Verdoes, X and Westerbeke, FHM and Meijer, RI and Gotthardt, M and de Vos, WM and Herrema, H and Nieuwdorp, M and Hanssen, NMJ},
title = {Autologous fecal microbiota capsules are safe and potentially preserve beta-cell function in individuals with type 1 diabetes.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2563155},
doi = {10.1080/19490976.2025.2563155},
pmid = {41047724},
issn = {1949-0984},
mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy ; *Insulin-Secreting Cells/physiology/metabolism ; Male ; Female ; Adult ; *Feces/microbiology ; Pilot Projects ; Capsules/administration & dosage ; *Fecal Microbiota Transplantation/adverse effects/methods ; Young Adult ; Middle Aged ; C-Peptide/blood/metabolism ; Adolescent ; Gastrointestinal Microbiome ; },
abstract = {This study investigated the safety and feasibility of daily ingestion of autologous lyophilized fecal microbiota capsules (a-LFMCs) for preserving beta-cell function in individuals with type 1 diabetes (T1D). We evaluated a-LFMC in an open-label, single-arm pilot study (NCT05323162) with 10 individuals with T1D. The study included a 3-month run-in period, 3 months of daily a-LFMC treatment, and a 3-month follow-up. Beta-cell function was assessed using mixed-meal stimulated C-peptide area under the curve (AUC). During the run-in period, beta-cell function significantly declined (mean ΔAUC -12.02 ± 5.09 nmol/L*min, p = 0.025). There was no decrease in beta-cell function during the a-LFMC treatment period (mean ΔAUC 0.76 ± 5.09 nmol/L*min, p = 0.88) and the follow-up period (mean ΔAUC 0.96 ± 5.09 nmol/L*min, p = 0.85). No serious adverse events occurred, though constipation increased during the treatment period (0% vs. 30%, p = 0.021). a-LFMC treatment was found to be safe and potentially contributes to preserving beta-cell function in T1D patients. A larger randomized placebo-controlled trial is needed to confirm these promising findings.},
}

Humans
*Diabetes Mellitus, Type 1/therapy
*Insulin-Secreting Cells/physiology/metabolism
Male
Female
Adult
*Feces/microbiology
Pilot Projects
Capsules/administration & dosage
*Fecal Microbiota Transplantation/adverse effects/methods
Young Adult
Middle Aged
C-Peptide/blood/metabolism
Adolescent
Gastrointestinal Microbiome

@article {pmid41046337,
year = {2025},
author = {Vogel, GF and Kathemann, S and Pietrobattista, A and Maggiore, G and Aldrian, D and Sciveres, M and Verkade, HJ and Sokal, E and Jannone, G and Salcedo, M and Rauschkolb, P and Maucksch, C and Valcheva, V and Lainka, E},
title = {Odevixibat after liver transplant in patients with progressive familial intrahepatic cholestasis type 1: A case series.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpn3.70227},
pmid = {41046337},
issn = {1536-4801},
support = {//Ipsen/ ; },
abstract = {OBJECTIVES: Patients with progressive familial intrahepatic cholestasis type 1 (PFIC1) who have undergone liver transplantation (LT) may have unmet needs and impacts on daily life due to post-LT complications, including diarrhea and hepatic steatosis. Here, we describe the effects of the ileal bile acid transporter inhibitor odevixibat on diarrhea and hepatic steatosis in a cohort of patients with PFIC1 post-LT.

METHODS: Treating physicians from six centers retrospectively collected data through July 2023 on patients with PFIC1 who received odevixibat post-LT. Data collected included demographics, medical history, and symptom presentation, characteristics of diarrhea, and liver imaging and/or histopathology.

RESULTS: Overall, nine male patients with PFIC1 (seven aged <18 years at initial completion of the case report form) were included. In most patients, the primary indication for odevixibat treatment was diarrhea and/or steatosis post-LT. Odevixibat was initiated at a daily dose of 30-120 µg/kg (median exposure: 13 months). All patients had post-LT diarrhea, which was generally associated with negative impacts on daily life (e.g., ability to attend school, needing to wear diapers due to fecal urgency). After odevixibat initiation, most patients had improved diarrhea and positive impacts on daily life. Among five patients with post-LT steatosis and data available before and after odevixibat initiation, steatosis appeared to improve in three and did not change in two.

CONCLUSIONS: Overall, the majority of patients with PFIC1 post-LT complications in this case series experienced improvements in diarrhea and daily activities with odevixibat. Treatment with odevixibat following LT also appeared to reduce steatosis in some patients. Further studies, particularly those with a prospective design, are needed to confirm these findings.},
}

@article {pmid41046274,
year = {2025},
author = {Sadeghloo, Z and Ebrahimi, S and Hakemi-Vala, M and Totonchi, M and Sadeghi, A and Fatemi, N},
title = {Fusobacterium nucleatum and non-coding RNAs: orchestrating oncogenic pathways in colorectal cancer.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {78},
pmid = {41046274},
issn = {1757-4749},
abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with mounting evidence implicating the gut microbiome in its pathogenesis. Among the microbial agents, Fusobacterium nucleatum has emerged as a prominent contributor, frequently detected in CRC tissues and associated with advanced disease stages and poor prognosis. This review highlights the complex interplay between F. nucleatum and host non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in modulating CRC biology. F. nucleatum influences the expression of several ncRNAs, which in turn regulate key signaling pathways such as Wnt/β-catenin (e.g., miR-1246, miR-135b), PI3K/AKT (e.g., miR-22, miR-135b), and TLR4/NF-κB (e.g., miR-31, lnc-NEAT1). Through these mechanisms, F. nucleatum contributes to tumor cell proliferation, immune evasion, metastasis, and chemoresistance. Additionally, its impact on ncRNA expression is implicated in reduced efficacy of standard chemotherapy. Emerging microbiota-based therapies, including probiotics and fecal microbiota transplantation, show promise in modulating gut flora and potentially reversing ncRNA dysregulation; however, their mechanistic effects on the F. nucleatum-ncRNA axis require further investigation. This review underscores the critical role of F. nucleatum-regulated ncRNAs in CRC and presents new opportunities for biomarker discovery and targeted therapeutics.},
}

@article {pmid41045390,
year = {2025},
author = {Senthilkumar, H and Chauhan, SC and Arumugam, M},
title = {Unraveling the multifactorial pathophysiology of polycystic ovary syndrome: exploring lifestyle, prenatal influences, neuroendocrine dysfunction, and post-translational modifications.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {980},
pmid = {41045390},
issn = {1573-4978},
mesh = {Humans ; *Polycystic Ovary Syndrome/physiopathology/metabolism/genetics/etiology ; Female ; *Protein Processing, Post-Translational ; Life Style ; Pregnancy ; Neurosecretory Systems/metabolism/physiopathology ; Insulin Resistance/physiology ; Animals ; Oxidative Stress ; },
abstract = {Polycystic ovary syndrome (PCOS) is a complex, multifactorial metabolic and endocrine disorder in reproductive-age women. This review discusses the interlinked roles of lifestyle, metabolic dysregulation, insulin resistance, neuroendocrine impairment, genetic predisposition, and post-translational modifications (PTMs) in PCOS pathogenesis. Lifestyle components, especially those leading to obesity and insulin resistance, worsen the hyperandrogenism, ovulatory dysfunction, and inflammation. Dietary treatments such as, DASH diet and caloric restriction, particularly along with metformin, have been proven to improve metabolic and reproductive parameters. Environmental toxins, such as endocrine-disrupting chemicals (EDCs) and advanced glycation end-products (AGEs), further compromise ovarian function and hormone regulation. Oxidative stress and insulin resistance, driven by mitochondrial malfunction and chronic inflammation, create a self-perpetuating vicious cycle that compromises oocyte quality and worsens metabolic imbalance. Neuroendocrine disruption, characterized by increased GnRH and LH pulsatility, is initiated by dysregulated kisspeptin, dynorphin, and neurokinin B signaling in KNDy neurons, modified GABAergic input, and increased AMH and androgens. PTMs such as phosphorylation, methylation, acetylation, and ubiquitination also play essential roles in granulosa cell function, AR signaling, insulin sensitivity, and oocyte maturation. Current and novel treatment options vary from lifestyle modifications and pharmacological interventions (e.g., metformin, GLP-1 receptor agonists, myoinositol, vitamin D, and statins) to regenerative measures like mesenchymal stem cells and fecal microbiota transplantation. Newer therapies focusing on PTMs and neuroendocrine regulators remain the future hope. Multidisciplinary individualized management is critical for successful PCOS therapy and averting long-term complications.},
}

Humans
*Polycystic Ovary Syndrome/physiopathology/metabolism/genetics/etiology
Female
*Protein Processing, Post-Translational
Life Style
Pregnancy
Neurosecretory Systems/metabolism/physiopathology
Insulin Resistance/physiology
Animals
Oxidative Stress

@article {pmid41039216,
year = {2025},
author = {Ma, Y and Wang, D and Yu, X and Fan, Y and Yang, Z and Gao, X and Huang, X and Meng, J and Cheng, P and Liu, X and Liu, Z and Li, X},
title = {Moderate altitude exposure induced gut microbiota enterotype shifts impacting host serum metabolome and phenome.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {591},
pmid = {41039216},
issn = {1471-2180},
support = {2023YFE0114300//National key research and development program intergovernmental key projects/ ; No.2024A1515012697//Guangdong Provincial Basic and Applied Basic Research Fund Project/ ; No. 202206010044//Science and Technology Program of Guangzhou, China/ ; No. U24A20652//The Joint Funds of the Natural Science Foundation of China/ ; No. 82272246//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Consistent patterns of gut microbiota variations, particularly in relative abundance, have been identified in the adult human gut. Enterotype, another general measure of the gut microbiota, is a valuable approach for categorizing the human gut microbiota into distinct clusters. The impact of different enterotypes on human health varies, and the changes induced by moderate altitude exposure remain unclear. This study aimed to conduct a comprehensive investigation of the cascade effects triggered by enterotype shifts following moderate altitude exposure.

RESULTS: Using shotgun metagenome sequencing, participants before and after moderate-altitude exposure were classified into cluster BL (dominated by Blautia) and cluster BA (dominated by Bacteroides). Relative to cluster BL, cluster BA consisted predominantly of individuals exposed to moderate altitude. Compared to cluster BL, Cluster BA exhibited rewired metabolism of serum metabolites (i.e., amino acids, fatty acids and bile acids) and gut microbiota, lower inflammatory factor levels (i.e., tumor necrosis factor-α (TNF-α)), and sparser correlations among these parameters. Individuals with baseline BL enterotype who transitioned to the BA enterotype following moderate-altitude exposure showed prominent improvement in fasting blood glucose (FBG) levels, with higher abundance of Bacteroidetes species (e.g., Bacteroides thetaiotaomicron, and Bacteroides uniformis), but lower Proteobacteria species abundance (e.g., Escherichia coli) and decreased L-Glutamic acid levels. Furthermore, fecal microbiota transplantation (FMT) from moderate-altitude exposed individuals to high-fat diet (HFD) fed mice confirmed increased Bacteroides abundance shifts associated with improvements in glucose homeostasis regulation and rewired amino acid metabolism. In addition, significant increases in alanine aminotransferase (ALT) levels but decreased serum creatinine (Scr), arterial oxygen saturation (SaO2), 4-Hydroxyproline, L-Glutamic acid, L-Asparagine, L-Threonine, L-Citrulline, L-Lysine and Isovaleric acid levels were identified as potentially important signals for individuals upon moderate altitude exposure, regardless of the gut microbiota enterotype.

CONCLUSIONS: Moderate altitude exposure could induce enterotype switching, and a Bacteroides-dominant enterotype may be a beneficial pattern of the gut microbiome related to host metabolism. Moderate-altitude exposure has potential implications for glycemic control, suggesting new avenues for managing FBG levels in future.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04245-4.},
}

@article {pmid41043596,
year = {2025},
author = {Nasare, D and Bagade, S},
title = {The Gut-Lung Axis in Tuberculosis: A New Frontier in Immunomodulation and Microbiota-Directed Therapeutic Strategies.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108087},
doi = {10.1016/j.micpath.2025.108087},
pmid = {41043596},
issn = {1096-1208},
abstract = {Tuberculosis (TB) is a transmissible disease that contributes to the global health burden due to drug resistance. The gut-lung axis is an emerging and promising frontier for understanding Mycobacterium tuberculosis (MTB) pathogenesis and disease progression via gut and lung bidirectional communication. Increasing evidence highlights that regulation in gut and lung microbial communities, termed dysbiosis, influences homeostatic conditions, innate and adaptive responses, and susceptibility to TB. Growing research has witnessed a paradigm shift toward the immunological interplay between gut microbiota and lung microbiota, and modulation in TB. This review deals with the interplay of immune cells and gut microbiota in TB, highlighting the importance of innate and adaptive responses in stabilizing the dysbiosis and inflammation. Host-directed therapies such as probiotics, prebiotics, synbiotics, short-chain fatty acids (SCFAs), and fecal microbiota transplantation support the stabilization of gut microbiota and maintain the disease severity. Moreover, personalized microbiota therapies, such as bacteriophage therapy, diagnostic agents, and biomarkers, are explored for their several roles in maintaining the eubiosis condition. We also highlight the future perspective of addressing the knowledge gap to develop a personalized and combined approach to novel drug delivery systems and host-directed therapies. This review provides an in-depth outline of the gut-lung axis as a potential therapeutic intervention, offering a conceptual framework for developing next-generation, microbiota-directed therapies to suppress and combat MTB infection.},
}

@article {pmid41043575,
year = {2025},
author = {Ahmed, LA and Al-Massri, KF},
title = {Insights into the Role of Gut Microbiota Modulation in the Management of Various Cardiovascular Diseases: A New Approach for Improving the Efficacy of Current Cardiovascular Medications.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178210},
doi = {10.1016/j.ejphar.2025.178210},
pmid = {41043575},
issn = {1879-0712},
abstract = {Gut microbiome is an emerging contributor to various cardiovascular diseases (CVDs) where gut dysbiosis increases the risk of development and progression of atherosclerosis, coronary artery diseases, hypertension, and heart failure. Microbiota can also affect the metabolism of medications including cardiovascular drugs, resulting in alteration of their pharmacokinetics and pharmacodynamics or producing metabolites which can interfere with response of these drugs. Importantly, CVDs require prolonged pharmacological interventions with medications which may have impacts on the diversity and composition of gut microbiota. Gut microbiota modulation using diets, prebiotics, probiotics, fecal microbiota transplantation, and microbial trimethylamine-lyase inhibitors, has also shown benefits in the management of CVDs where gut microbiota and their metabolites have recently been studied as potential targets for the management of these diseases. Specifically, using innovative microbiota therapies in combination with traditional pharmacological agents have been evaluated for additional benefits in various CVDs. However, assessing the interactions among host factors, gut microbiome, and drug response will be essential for the development of new therapeutic targets for cardiovascular disorders, ultimately hoping better prognosis and patient's quality of life for those affected with CVDs.},
}

@article {pmid41043062,
year = {2025},
author = {Malogan, J and Hallowell, HA and Francis, B and Suez, J},
title = {Supplementation and Elimination of Microbiome-Produced Metabolites in the Treatment of Human Disease.},
journal = {Annals of the New York Academy of Sciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/nyas.70103},
pmid = {41043062},
issn = {1749-6632},
abstract = {The human gut microbiome has a complex and influential relationship with host physiology that is governed through commensal-derived metabolites, small molecules, and endogenous microbial patterns. Indeed, microbial metabolites from the gut microbiome have been implicated in promoting health as well as contributing to the pathogenesis of microbiome-associated diseases. Live microbial therapeutics, such as probiotics and fecal microbiota transplantations, have been extensively utilized to establish health-promoting assemblages of bacteria and their associated beneficial metabolites. However, broad clinical use of live microbial therapeutics is limited by efficacy, specificity, and safety concerns. To circumvent this, a postbiotic approach can be taken, in which a beneficial effect may be achieved by direct administration of bacterially derived bioactive molecules. Alternatively, in cases where microbiome-derived metabolites drive disease, specific oral inhibitors can be used to restrict compound production. In this review, we examine the use of postbiotics to alleviate disease and highlight recent translational successes. Additionally, we discuss emerging approaches for precision elimination of disease-causing metabolites, as well as the exciting possibility of utilizing bacteriophages to modulate the production of metabolites in the microbiome.},
}

@article {pmid41041846,
year = {2025},
author = {Zhao, Y and Yu, C and Zhang, J and Yao, Q and Zhu, X and Zhou, X},
title = {The gut‑skin axis: Emerging insights in understanding and treating skin diseases through gut microbiome modulation (Review).},
journal = {International journal of molecular medicine},
volume = {56},
number = {6},
pages = {},
doi = {10.3892/ijmm.2025.5651},
pmid = {41041846},
issn = {1791-244X},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Skin Diseases/therapy/microbiology ; *Skin/microbiology/pathology ; Probiotics/therapeutic use ; Animals ; Prebiotics ; },
abstract = {Emerging evidence indicates a significant association between the composition and functionality of the gut microbiome and various skin disorders, including psoriasis, atopic dermatitis, acne and several dermatological conditions. The gut‑skin axis theory describes a complex bidirectional communication network between the gut and the skin, providing mechanistic insights into the pathogenesis of certain cutaneous diseases. Specifically, the gut microbiome influences skin health through the regulation of systemic immunity, inflammatory responses and metabolic pathways. Advances in high‑throughput sequencing and bioinformatics technologies have substantially enhanced the understanding of the role of the gut microbiome in skin pathology. Clinical and preclinical studies have demonstrated that restoring gut microbial homeostasis via interventions such as faecal microbiota transplantation, probiotics and prebiotics can ameliorate symptoms of skin diseases. Furthermore, personalized microbiome‑based therapies, next‑generation probiotics and dietary modifications hold promise for refining gut‑skin interactions and advancing precision medicine in dermatology. Therapeutic strategies targeting the gut‑skin axis offer novel avenues for innovative dermatological treatments, with future breakthroughs potentially involving microbial community engineering, postbiotics and artificial intelligence in microbiome‑related diagnostics. This narrative review summarizes recent advances in gut‑skin axis research, explores its potential in the prevention and management of selected dermatoses and discusses future trends and scientific developments in the field.},
}

Humans
*Gastrointestinal Microbiome
*Skin Diseases/therapy/microbiology
*Skin/microbiology/pathology
Probiotics/therapeutic use
Animals
Prebiotics

@article {pmid41041667,
year = {2025},
author = {Tariq, H and Ramakrishnan, M and Portocarrero, P and Gupta, M and Herrera, N and Klein, J and Gupta, A and Cibrik, D},
title = {Fecal Impaction: An Unusual Cause of Acute Kidney Injury in a Kidney Transplant Recipient.},
journal = {Case reports in transplantation},
volume = {2025},
number = {},
pages = {5726025},
pmid = {41041667},
issn = {2090-6943},
abstract = {Acute kidney injury (AKI) is common in kidney transplant recipients, and the etiology varies depending on the time since transplantation. We present an uncommon case of AKI from obstructive uropathy 7 years posttransplant in a 47-year-old Caucasian male with moderate intellectual disability and end-stage kidney disease secondary to glomerulonephritis who received a deceased donor kidney transplant. He presented with abdominal pain, lethargy, hypercalcemia, and AKI. However, though his serum calcium level improved with intravenous fluid resuscitation, the AKI did not improve. Kidney transplant ultrasound showed hydronephrosis of the transplant ureter, and a noncontrast abdominal and pelvic computed tomography scan showed fecal impaction as the cause of obstruction of the transplanted ureter. The patient underwent fecal disimpaction resulting in the resolution of his hydronephrosis and return of his kidney function to baseline. Although a few case reports have been published of fecal impaction causing AKI due to obstruction of native ureters, to our knowledge, this is the first case describing AKI from fecal impaction in an adult kidney transplant recipient.},
}

@article {pmid41041075,
year = {2025},
author = {Zhu, S and Li, X and Yu, Y and Han, X and Yang, F and Lu, M and Dai, G and Guo, L and Xu, D},
title = {EZH2-mediated H3K27me3 links microbial inosine loss to depression: a gut-brain epigenetic switch.},
journal = {Theranostics},
volume = {15},
number = {18},
pages = {9969-9986},
pmid = {41041075},
issn = {1838-7640},
mesh = {Animals ; *Gastrointestinal Microbiome/genetics/physiology ; Mice ; *Enhancer of Zeste Homolog 2 Protein/metabolism/genetics ; *Epigenesis, Genetic ; *Depression/microbiology/metabolism/genetics ; *Histones/metabolism ; *Inosine/metabolism ; *Brain/metabolism ; Male ; Mice, Knockout ; Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Apoptosis ; },
abstract = {Background: Depression, the second most prevalent neurological disorder globally, affects over 300 million people and presents an urgent public health challenge. While gut microbiota dysbiosis is increasingly recognized as a key contributor to depression, the molecular mechanisms linking microbial imbalance to brain dysfunction remain poorly defined. Methods: We investigated the role of EZH2 in gut microbiota-induced depressive behaviors in mice using the chronic unpredictable mild stress (CUMS), fecal microbiota transplantation, and conditional knockout of EZH2. CUT&Tag sequencing was employed to analyze EZH2-mediated H3K27me3 epigenetic reprogramming. Untargeted metabolomics and luciferase reporter assays were used to identify metabolites that upregulate EZH2 expression. 16S rRNA sequencing combined with metabolic tracing was conducted to trace the microbial origin of inosine. Additionally, natural compound screening identified coumaric acid (CA) as a novel EZH2-targeting degrader. Results: Conditional knockout of neuronal Ezh2 abolishes microbiota-induced depressive behaviors and neuronal apoptosis. Mechanistically, reduced abundance of specific microbiota (f_Lachnospiraceae, f_Oscillospiraceae, and f_Erysipelotricaceae) leads to inosine depletion. This depletion subsequently elevates EZH2 transcriptional activity by increasing H3K9ac modification at its locus, mediated through attenuation of the A2aR-cAMP-PKA-CREB-HDAC3 signaling axis. Subsequently, EZH2 silences serotonergic synapse-related genes (e.g., Tph2, Htr2a, Htr6) via H3K27me3 reprogramming, ultimately driving depressive behaviors and neuronal apoptosis in mice. Importantly, CA is identified as a first-in-class EZH2 degrader that binds lysine residues K623/K646 and recruits UBE3A for proteasomal degradation. CA treatment restores synaptic integrity and reverses depressive behaviors with minimal toxicity. Conclusions: Collectively, these findings define a novel "microbiota-inosine-EZH2" axis in depression pathogenesis and highlight EZH2 degradation as a promising therapeutic strategy for microbiota-associated neuropsychiatric disorders.},
}

Animals
*Gastrointestinal Microbiome/genetics/physiology
Mice
*Enhancer of Zeste Homolog 2 Protein/metabolism/genetics
*Epigenesis, Genetic
*Depression/microbiology/metabolism/genetics
*Histones/metabolism
*Inosine/metabolism
*Brain/metabolism
Male
Mice, Knockout
Mice, Inbred C57BL
Disease Models, Animal
Dysbiosis/microbiology
Fecal Microbiota Transplantation
Apoptosis

@article {pmid41040884,
year = {2025},
author = {Zhang, S and Zhang, T and Zhang, Y and Ye, C and Mu, L and He, Q and Huang, T and Wang, G and Li, Y and Xie, S and Tang, X},
title = {Akkermansia muciniphila regulates the gut microenvironment and alleviate periodontal inflammmation in mice with periodontitis.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1643691},
pmid = {41040884},
issn = {1664-302X},
abstract = {OBJECTIVE: Akkermansia muciniphila (A. muciniphila) is an emerging gut commensal known for its roles in host metabolism and immune modulation. While its involvement in metabolic and inflammatory disorders is well characterized, its potential association with oral diseases such as periodontitis remains poorly understood. This study aimed to explore whether modulation of the gut microbiota via fecal microbiota transplantation (FMT) from periodontally healthy donors could influence the abundance of A. muciniphila and contribute to the alleviation of periodontitis.

METHODS: Fecal samples were collected from human donors, including periodontally healthy individuals (H group, n = 16), untreated patients with severe periodontitis (P group, n = 12), and the same patients at two weeks (P2W) and three months (P3M) after periodontal therapy. Quantitative PCR was used to assess A. muciniphila abundance in these human samples. A germ-free mouse model of periodontitis was then established, and the mice received FMT using samples from human donor groups (P-PBS, P-H, and P-P). Gut microbiota composition, periodontal inflammation, gut barrier proteins (MUC2, ZO-1), and inflammatory cytokines (IL-6, TNF-α) were evaluated in the mice.

RESULTS: Compared to groups H, P2W, and P3M, the abundance of A. muciniphila in the gut was significantly lower in patients with severe periodontitis, but it was increased after periodontal therapy. In mice, FMT from healthy donors (P-H group) significantly enriched A. muciniphila, improved expression of gut barrier proteins, reduced inflammatory cytokine levels, and alleviated periodontal inflammation compared to other groups.

CONCLUSION: These findings suggest a previously underrecognized link between gut microbial composition particularly A. muciniphila and periodontal health. Targeting the gut microbiota via FMT may represent a novel strategy for modulating systemic and oral inflammation and supporting the prevention or adjunctive treatment of periodontitis.},
}

@article {pmid41039491,
year = {2025},
author = {Song, J and Yang, X and Liu, X and Li, J},
title = {Gut bacteria: protective mediators, pathogenic contributors and novel therapeutic targets in Candida albicans infections.},
journal = {Gut pathogens},
volume = {17},
number = {1},
pages = {77},
pmid = {41039491},
issn = {1757-4749},
support = {24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; },
abstract = {Candida albicans is an opportunistic pathogen that resides in the human gut alongside a diverse array of microorganisms, including enteric bacteria, archaea, and viruses, which collectively form the gut microbiota. Recent studies have shown that the development of Candida albicans infections involves both weakened host immunity and enhanced invasiveness of Candida albicans, with intestinal microecology serving as a critical mediator of these processes. It has been demonstrated that disturbances in the gut microbiome can potentiate the invasive capacity of Candida albicans. Moreover, a compromised immune system, along with the use of antibiotics and immunosuppressive drugs, can lead to gut microbiome imbalances. Consequently, modulators of the intestinal microecology represent promising therapeutic interventions for managing Candida albicans infections. In this review, we examine the mechanisms underlying the increased invasiveness of Candida albicans following significant disruption of intestinal bacteria and highlighting the interplay among immune dysfunction, antibiotic use, and their effects on gut microbiome imbalance and Candida albicans infection. Additionally, we summarize the roles of microbiome-based therapies, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), in addressing Candida albicans infections. This review provides a theoretical foundation and practical guidance for the development of more effective microecological therapeutic strategies in the future.},
}

@article {pmid41039079,
year = {2025},
author = {Barkai, T and Yakubovsky, O and Korem Kohanim, Y and Bahar Halpern, K and Shir, S and Oren, N and Fine, M and Kelmer, P and Talmon, A and Israeli, A and Pencovich, N and Pery, R and Nachmany, I and Itzkovitz, S},
title = {Transcriptomic profiling of shed cells enables spatial mapping of cellular turnover in human organs.},
journal = {Molecular systems biology},
volume = {},
number = {},
pages = {},
pmid = {41039079},
issn = {1744-4292},
support = {768956//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; 908/21//Israeli Science Foundation/ ; 3663/21//Israeli Science Foundation/ ; },
abstract = {Single-cell atlases provide valuable insights into gene expression states but lack information on cellular dynamics. Understanding cell turnover rates-the time between a cell's birth and death-can shed light on stemness potential and susceptibility to damage. However, measuring turnover rates in human organs has been a significant challenge. In this study, we integrate transcriptomic data from both tissue and shed cells to assign turnover scores to individual cells, leveraging their expression profiles in spatially resolved expression atlases. By performing RNA sequencing on shed cells from the upper gastrointestinal tract, collected via nasogastric tubes, we infer turnover rates in the human esophagus, stomach, and small intestine. In addition, we analyze colonic fecal washes to map turnover patterns in the human large intestine. Our findings reveal a subset of short-lived, interferon-stimulated colonocytes within a distinct pro-inflammatory microenvironment. Our approach introduces a dynamic dimension to single-cell atlases, offering broad applicability across different organs and diseases.},
}

@article {pmid41038971,
year = {2025},
author = {Bahar Halpern, K and Kent, I and Yakubovsky, O and Ben-Moshe, S and Barkai, T and Fine, M and Novoselsky, R and Israeli, A and Nachmany, I and Itzkovitz, S},
title = {Stool shed cell transcriptomics mirrors tumor biology and enables colorectal cancer diagnosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34413},
pmid = {41038971},
issn = {2045-2322},
support = {768956/ERC_/European Research Council/International ; },
mesh = {Humans ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; *Feces/cytology ; Female ; *Transcriptome ; Male ; *Gene Expression Profiling/methods ; Aged ; Middle Aged ; Biomarkers, Tumor/genetics ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Early Detection of Cancer/methods ; },
abstract = {Screening and molecular characterization of human intestinal pathologies such as colorectal cancer (CRC) currently depends on colonoscopy, an invasive procedure associated with risks and poor adherence. A non-invasive method that captures host molecular changes could improve early detection and monitoring of intestinal diseases. Transcriptomic profiling of shed intestinal cells in stool has shown potential in neonates but is limited in adults by the dominance of bacterial RNA. To address this, we combined microbial ribosomal RNA (rRNA) depletion with unique molecular identifier (UMI)-based RNA sequencing to enrich and quantify human transcripts in stool. Applying this method to samples from 54 CRC patients and 24 healthy controls, we profiled thousands of human genes per sample. Stool-derived gene expression distinguished CRC from control samples with high accuracy (AUC = 0.86) and strongly correlated with matched tumor tissue signatures. Notably, stool transcriptomes reverted to control-like patterns after tumor resection. Our approach offers a powerful, non-invasive alternative to current CRC diagnostics and enables molecular insights into tumor biology. This method could complement or replace existing screening tools and may be applicable to other gastrointestinal diseases.},
}

Humans
*Colorectal Neoplasms/diagnosis/genetics/pathology
*Feces/cytology
Female
*Transcriptome
Male
*Gene Expression Profiling/methods
Aged
Middle Aged
Biomarkers, Tumor/genetics
Case-Control Studies
Gene Expression Regulation, Neoplastic
Adult
Early Detection of Cancer/methods

@article {pmid41038411,
year = {2025},
author = {Taoum, C and Devaux, A and Rouanet, P and Colombo, PE and Boucher, D and Bonnet, M},
title = {Gut microbiota and chemoradiotherapy response in rectal cancer: biomarker opportunities.},
journal = {Critical reviews in oncology/hematology},
volume = {},
number = {},
pages = {104974},
doi = {10.1016/j.critrevonc.2025.104974},
pmid = {41038411},
issn = {1879-0461},
abstract = {The gut microbiota is increasingly recognized as a key factor in rectal carcinogenesis. This review synthesizes current clinical and preclinical evidence linking specific microbial signatures, such as Fusobacterium nucleatum, Duodenibacillus massiliensis and colibactin-producing Escherichia coli (CoPEC) to chemoradiotherapy (CRT) treatment efficacy and resistance. Microbiota-driven mechanisms include immune modulation, inflammation, and drug metabolism. We highlight emerging microbial biomarkers and therapeutic strategies such as antibiotics, probiotics, and fecal microbiota transplantation. Integrating microbiome profiling into clinical workflows could refine patient stratification and enhance CRT efficacy in rectal cancer. Ongoing clinical trials aim to validate these associations and establish robust microbial biomarkers for CRT response prediction in rectal cancer.},
}

@article {pmid41038146,
year = {2025},
author = {Du, Y and Xu, J and Jia, J and Nong, Y and Lin, Y and Ye, Y and Zhong, Y and Tan, Q and Wei, Y and Huang, G and Mao, D and Huang, G and Lu, L and Peng, Y and Huang, H and Huang, J},
title = {Yuzhuo Zhixiao pill can treat non-alcoholic steatohepatitis through modulation of gut microbiota, bile acid and short-chain fatty acid metabolism.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157348},
doi = {10.1016/j.phymed.2025.157348},
pmid = {41038146},
issn = {1618-095X},
abstract = {BACKGROUND: Yuzhuo Zhixiao Pill (YZZXP), a formulation in traditional Chinese medicine (TCM), exhibits therapeutic potential in non-alcoholic steatohepatitis (NASH). However, the mechanisms underlying its effects, particularly those involving gut microbiota-bile acid-short-chain fatty acid (GM-BA-SCFA) interactions, remain unclear. Current therapies present notable side effects and inadequately address the multifactorial etiology of NASH.

PURPOSE: To evaluate the anti-NASH efficacy of YZZXP and elucidate its mechanism, focusing on GM remodeling and BA/SCFA regulation.

STUDY DESIGN: This study established a NASH model in rats using a high-fat diet (HFD) and performed fecal microbiota transplantation (FMT) experiments.

METHODS: The therapeutic impacts of YZZXP on gut microbial structure (16S rDNA sequencing), SCFA concentrations, and BA profiles (analyzed by LC-MS and GC-MS) were assessed.

RESULTS: YZZXP administration alleviated HFD-induced obesity, hepatic steatosis, inflammatory responses, and disturbances in glycolipid metabolism. Microbial profiling via 16S rDNA sequencing revealed restored gut microbial diversity, marked by increased Akkermansia, Bacteroides, and Roseburia abundance. PROB and FMT interventions validated GM modulation as central to YZZXP 's effects. Targeted metabolomic analyses demonstrated elevated levels of SCFAs (notably butyrate and acetate) and substantial shifts in BA composition, accompanied by downregulation of intestinal FXR-FGF19 signaling and enhanced cholesterol excretion.

CONCLUSIONS: YZZXP exerts anti-NASH activity through a synergistic mechanism comprising GM restoration, BA metabolic reprogramming via FXR pathway inhibition, and SCFA-driven metabolic modulation. In contrast to monotherapy approaches, the multi-target strategy of YZZXP prevents compensatory dysbiosis and yields more durable metabolic benefits than PROB or FMT alone. By integrating microbiota-metabolite interplay into therapeutic design, YZZXP introduces a novel paradigm in traditional medicine for NASH management, addressing the limitations of synthetic agents while promoting metabolic homeostasis.},
}

@article {pmid41038145,
year = {2025},
author = {Guo, L and Yi, J and Zhang, A and Zheng, X and Wang, M and Yang, F and Kong, X and Meng, J},
title = {Zhenqi Fuzheng Granule targets the SCFAs-GPR109A axis to enhance PD-1 antibody efficacy via immunometabolic remodeling in colorectal cancer.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157312},
doi = {10.1016/j.phymed.2025.157312},
pmid = {41038145},
issn = {1618-095X},
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs), particularly PD-1 antibodies, represent a breakthrough in colorectal cancer (CRC) treatment. However, their clinical efficacy remains limited by tumour-induced immunosuppression. Traditional Chinese medicine (TCM) has attracted growing interest as a potential adjuvant to immunotherapy. Zhenqi Fuzheng Granule (ZQFZ) is a clinically approved herbal prescription widely used as an adjuvant therapy for CRC, yet its mechanistic underpinnings remain elusive.

OBJECTIVE: To investigate how ZQFZ improves the efficacy in CRC, with emphasis on gut microbiota modulation, SCFAs production, and downstream immunometabolic pathways involving GPR109A, and confirms that butyrate plays an important role in colorectal cancer inhibition.

METHODS: Phytochemical analysis of ZQFZ was conducted using LC-MS/MS and UPLC-MS/MS, identifying and quantifying seven major compounds. In vivo experiments, AOM/DSS-induced CRC mouse models were treated with ZQFZ, PD-1 antibody, or their combination. Tumour progression, body weight, and survival were monitored. Gut microbial composition and colonic SCFAs levels were assessed via 16S rRNA sequencing and gas chromatography. RT-qPCR was employed to validate the expression of key genes associated with the GPR109A/AKT/mTOR/HIF-1α signaling pathway. Molecular changes in the GPR109A/AKT/mTOR/HIF-1α pathway were evaluated through Western blotting, transcriptomic, and proteomic analyses. Immune cell infiltration and phenotypes were analyzed by flow cytometry. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and structural stability between GPR109A and AKT1. The interactions between GPR109A and AKT1, as well as between butyrate and GPR109A, were further validated in vitro using microscale thermophoresis (MST) assays. To evaluate the microbial basis of ZQFZ activity, antibiotic-pretreated mice received ZQFZ-derived fecal microbiota transplantation (FMT). In vitro experiments, to investigate the mechanism by which sodium butyrate (NaB), the major gut microbial metabolite of ZQFZ, inhibits glycolysis in colorectal cancer under hypoxic conditions, CCK-8 assays, flow cytometry, lactate measurements, and Western blotting were performed to assess cell viability, apoptosis, lactate production, and the expression of AKT/mTOR/HIF-1α and glycolysis-related proteins.

RESULTS: LC-MS/MS profiling identified multiple bioactive constituents in ZQFZ. Targeted UPLC-MS/MS quantification revealed that the formulation contained Adenosine (0.87mg/g), Salidroside (0.11 mg/g), Astragaloside IV (0.07 mg/g), Calycosin (0.03 mg/g), Formononetin (6.7 μg /g), Chlorogenic acid (1.4 μg/g), Apigenin (0.5 μg/g). In vivo studies, both ZQFZ and PD-1 antibody inhibited tumour growth, with the combination treatment exerting the most pronounced antitumour effects. ZQFZ reshaped the gut microbiota, increased the levels of short-chain fatty acids (SCFAs), particularly butyrate, and activated the GPR109A pathway, leading to downregulation of the AKT/mTOR/HIF-1α signaling axis, suppression of HK2 expression and lactate production, and consequent inhibition of glycolysis. Immune remodeling was also observed, including reduced infiltration of myeloid-derived suppressor cells (MDSCs), polarization of macrophages toward the M1 phenotype, restoration of the CD4⁺/CD8⁺ T cell ratio, and modulation of serum cytokines including upregulation of IL-2, IL-12, and IFN-γ, along with downregulation of IL-4 and IL-10. ZQFZ-derived FMT significantly inhibited tumour growth, suppressed glycolysis-related markers (PKM2, GLUT1, HIF-1α, LDHA), and remodeled the immune microenvironment by reducing MDSCs and enhancing M1 macrophages and CD8⁺ T cell infiltration. In hypoxia-mimicking in vitro experiments, sodium butyrate (NaB), the principal gut microbial metabolite of ZQFZ, suppressed colorectal cancer cell viability and induced apoptosis. Through activation of GPR109A, NaB inhibited the AKT/mTOR/HIF-1α pathway and glycolysis-related enzymes, reduced lactate production, and further suppressed glycolysis. Molecular docking and dynamics simulations suggested a stable interaction between GPR109A and AKT1, which was confirmed in vitro by MST showing high-affinity binding (Kd=74.5 ± 20.8 nM); MST also verified moderate-affinity binding between GPR109A and sodium butyrate (Kd=43.3 ± 6.5 μM), supporting a dual interaction model wherein butyrate activates GPR109A, which in turn directly binds AKT1 to inhibit downstream glycolytic signaling.

CONCLUSION: This study uncovers a novel integrated mechanism whereby ZQFZ enhances PD-1 antibody efficacy via the gut microbiota-SCFAs-GPR109A axis, and NaB-mediated glycolysis inhibition under hypoxia further confirms its immunometabolic mechanism against CRC.},
}

@article {pmid41037658,
year = {2025},
author = {Sun, W and Ma, L and Feng, X and Fan, Y and Cai, Y and Li, X},
title = {Efficacy of gut microbiota-based therapy for autism Spectrum Disorder and attention Deficit Hyperactivity Disorder: a systematic review and meta-analysis.},
journal = {Psychology, health & medicine},
volume = {},
number = {},
pages = {1-25},
doi = {10.1080/13548506.2025.2565181},
pmid = {41037658},
issn = {1465-3966},
abstract = {The gut-brain axis is an emerging therapeutic target for neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). However, the overall efficacy of gut microbiome-based interventions remains unclear. This systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, aimed to synthesize the evidence on these interventions. Fifteen randomized controlled trials (RCTs) were identified from 1,080 records across PubMed, Embase, Web of Science, Cochrane, PsycInfo, MEDLINE, and ClinicalTrials.gov through August 2024. Interventions included probiotics, prebiotics, dietary changes, and fecal transplants. Using random-effects models, pooled analysis showed a small but significant overall benefit of gut microbiota-based interventions (Standardized Mean Difference, SMD = -0.12; 95% Confidence Interval, CI: -0.19 to -0.04), with low heterogeneity (I[2] = 5.9%). Effects differed by disorder: ADHD demonstrated greater improvement (SMD = -0.24; 95% CI: -0.42 to -0.06; I[2] = 50.4%) compared to ASD (SMD = -0.05; 95% CI: -0.15 to 0.04; I[2] = 0%). Duration-specific effects emerged: 8-week interventions showed significant outcomes (SMD = -0.32; 95% CI: -0.58 to -0.06), while shorter or longer durations lacked significance. Acceptability analysis from eight studies revealed comparable dropout rates between intervention and control groups (ASD: Risk Ratio, RR = 1.002; ADHD: RR = 0.943), with no serious adverse events reported. Subgroup analyses identified participant age, diagnosis type, and geographic location as heterogeneity sources. Despite methodological limitations and small sample sizes, findings suggest gut microbiome modulation may offer a safe adjunctive therapy, particularly for ADHD, with optimal effects emerging at 8 weeks. The gut-brain axis appears promising for neurodevelopmental disorders, but current evidence remains preliminary. Future research should prioritize large-scale RCTs with standardized protocols, mechanistic investigations, and long-term follow-up to establish clinical guidelines and clarify biological pathways. Findings underscore the need to tailor interventions to specific disorders and optimize treatment duration.},
}

@article {pmid41036798,
year = {2025},
author = {Nobel, YR and Park, H and Tillman, AM and Seeram, D and Moallem, DH and Intara, A and Nandakumar, R and Annavajhala, MK and Gomez-Simmonds, A and Verna, EC and Uhlemann, AC},
title = {Fecal Microbiota and Bile Acid Profiles in Early-Stage Hepatocellular Carcinoma: A Matched Case-Control Study.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000000928},
pmid = {41036798},
issn = {2155-384X},
abstract = {INTRODUCTION: Early identification of hepatocellular carcinoma (HCC) is critical to reduce mortality. Diagnostic tools are limited for early disease. Intestinal microbiota may contribute to HCC risk directly and via metabolites, particularly bile acids (BA), offering potential noninvasive biomarkers.

METHODS: This was a case-control study of patients with cirrhosis with or without early-stage HCC, matched based on liver disease severity. Comprehensive analyses of fecal microbiota composition and function were performed.

RESULTS: There were 98 patients in the study (49 patients per group). Subjects with HCC were older (median 64 vs. 60 years, p<0.01) and more likely to have Hepatitis C (78% vs. 43%, p<0.01). Alpha diversity, beta diversity, and genes and pathways related to BA metabolism did not differ between groups overall, but alpha diversity did differ within the subset of patients with metabolic-associated steatotic liver disease (MASLD). There was differential abundance of multiple taxa between groups, including higher abundance of Klebsiella pneumoniae in cases. Increased concentration of secondary BA, which are microbiota-dependent, was associated with higher odds of HCC (adjusted OR 2.4, p=0.02); however, addition of microbial or BA features to a model with clinical data alone did not improve HCC prediction.

DISCUSSION: When accounting for liver disease severity, there were limited differences in intestinal microbiota composition and BA metabolism between subjects with or without early-stage HCC. Promising areas for future study of microbiota-based HCC biomarkers were identified, including a focus on the subpopulation of patients with MASLD.},
}

@article {pmid41036738,
year = {2025},
author = {Li, Y and Dong, J and Wang, S and Xiong, R and Kang, X},
title = {High flavonoid diet alleviates chronic stress in cancer patients by optimization of the gut microbiota.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo02560e},
pmid = {41036738},
issn = {2042-650X},
abstract = {Scope: Cancer patients face long-term psychological stress due to the fear of death, economic burden, and pain caused by the disease. The aim of this study is to explore the effects of flavonoid diets on chronic stress in cancer patients. Methods and results: In this study, cancer patients were subjected to a high flavonoid diet (n = 15) or normal diet (n = 15). Their chronic stress status, quality of life and immune function were evaluated at the beginning and end of a 12-week diet intervention. The high flavonoid diet significantly alleviated anxiety, depression, and perceived stress in cancer patients (p < 0.05). The stress indicators in their plasma and saliva also decreased after the flavonoid diet (p < 0.05). The anxiety and depression behaviors of mice improved after receiving fecal microbiota transplantation from cancer patients receiving a high flavonoid diet (p < 0.05). The distribution of the gut microbiota changed, and butyric acid levels increased significantly in the FMT mice from the high flavonoid group (p < 0.05). The selected components of flavonoid (quercetin) caused similar changes in the behavioral experiments and gut microbiota of chronic stress mice. Conclusion: High levels of flavonoid intake can significantly improve the chronic stress status and quality of life of cancer patients, and the effects may be mediated by the optimization of the gut microbiota and their metabolites.},
}

@article {pmid41036224,
year = {2025},
author = {Liu, T and Ou, G and Wu, J and Wang, S and Wang, H and Wu, Z and Jiang, Y and Chen, Y and Xu, H and Deng, L and Chen, X and Xu, L},
title = {Pingwei Powder alleviates high-fat diet-induced colonic inflammation by modulating microbial metabolites SCFAs.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1628488},
pmid = {41036224},
issn = {2235-2988},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Fatty Acids, Volatile/metabolism ; Colon/pathology/drug effects/microbiology ; *Colitis, Ulcerative/drug therapy ; Male ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; Cytokines/metabolism ; Disease Models, Animal ; Signal Transduction/drug effects ; Powders ; Mice, Inbred C57BL ; Bacteria/metabolism/classification/genetics ; Inflammation/drug therapy ; RNA, Ribosomal, 16S/genetics ; TOR Serine-Threonine Kinases/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; },
abstract = {BACKGROUND: Pingwei Powder (PWP), a renowned traditional Chinese medicine (TCM) formula, it has demonstrated excellent therapeutic effects in ulcerative colitis (UC), yet its underlying pharmacological mechanisms remain unclear. This study aims to investigate the therapeutic effect of PWP on the aggravation of colonic inflammation induced by a high-fat diet and particularly focuses on its regulatory mechanisms on gut microbiota, which are closely related to UC.

METHODS: Network pharmacology analysis was employed to screen potential pharmacological targets of PWP for UC. Histological changes in colonic tissue were observed using hematoxylin and eosin (H&E) staining, and immunofluorescence staining was performed to evaluate the expression of tight junction proteins (ZO1 and Occludin). Western blotting was used to detect the expression levels of proteins related to the PI3K/AKT/mTOR pathway, ZO1, and Occludin. qRT-PCR was conducted to measure the relative expression of inflammatory cytokines (IL-1β, IL-17, IL-6, and TNF-α) in colonic tissue. Additionally, 16S rDNA sequencing was performed to analyze gut microbiota alterations, and GC/MS was used to quantify short-chain fatty acids (SCFAs) in gut contents. The gutMgene database was utilized to validate the mediating roles of gut microbiota metabolites in the pharmacological effects of PWP. And their mediating role in PWP efficacy was verified by fecal microbiota transplantation (FMT) and butyrate supplementation.

RESULTS: Network pharmacology analysis predicted that PWP may regulate the PI3K/AKT pathway to exert therapeutic effects in UC. Experimental validation showed that PWP significantly downregulated the levels of PI3K, pAKT/AKT, and pmTOR/mTOR in colonic tissue, thereby enhancing autophagy in colonic epithelial cells, as evidenced by decreased levels of P62 and increased LC3B-II/LC3B-I ratios. Furthermore, 16S rDNA sequencing combined with targeted SCFAs analysis of gut contents revealed that the pharmacological effects of PWP may be mediated by increasing the abundance of SCFAs-producing gut microbiota (Alistipes and Parabacteroides) and elevating the levels of SCFAs in the gut.

CONCLUSION: PWP enhances the abundance of SCFAs-producing bacteria (Alistipes and Parabacteroides) in the gut, increases the levels of butyrate, and inhibits the PI3K/AKT/mTOR pathway in the colon. These effects promote colonic autophagy and contribute to the resolution of colonic inflammation.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Diet, High-Fat/adverse effects
*Fatty Acids, Volatile/metabolism
Colon/pathology/drug effects/microbiology
*Colitis, Ulcerative/drug therapy
Male
*Drugs, Chinese Herbal/pharmacology/therapeutic use
Mice
Cytokines/metabolism
Disease Models, Animal
Signal Transduction/drug effects
Powders
Mice, Inbred C57BL
Bacteria/metabolism/classification/genetics
Inflammation/drug therapy
RNA, Ribosomal, 16S/genetics
TOR Serine-Threonine Kinases/metabolism
Phosphatidylinositol 3-Kinases/metabolism

@article {pmid41035886,
year = {2025},
author = {Tayyab, M and Zhao, Y and Zhang, Y},
title = {Microbiome engineering to enhance disease resistance in aquaculture: current strategies and future directions.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1625265},
pmid = {41035886},
issn = {1664-302X},
abstract = {Aquaculture, a cornerstone of global food security, faces critical threats from disease outbreaks, antimicrobial resistance, and ecological disruption. Through a narrative analysis of over 160 studies, this review synthesizes advances in microbiome engineering-a sustainable approach to enhancing disease resistance in aquatic animals-addressing key gaps: the inconsistent efficacy of conventional probiotics and prebiotics under field conditions, and the need for climate-resilient solutions. Critically, we highlight the emergence of precision microbiome engineering as a transformative paradigm. We integrate findings from genomics, metabolomics, clustered regularly interspaced short palindromic repeats, and artificial intelligence to identify microbial strategies that enhance host resilience. Genomic and multi-omics methods reveal health-associated microbes and metabolites, such as Vibrio-dominated dysbiosis markers in shrimp and butyrate-mediated immunity. Guided by these biomarkers, we describe precision-tailored probiotics-host-derived or genome-edited Bacillus subtilis strains whose adhesion factors, metabolic outputs (e.g., butyrate, bacteriocins), and heat stress tolerance are matched to the target species' gut niche. These are combined with complementary prebiotics (e.g., chitosan oligosaccharides) and synbiotics (e.g., Lactiplantibacillus plantarum plus king oyster mushroom extracts) that suppress pathogens through competitive exclusion and immune modulation. Ecologically rational innovations-interventions explicitly grounded in ecological theory (niche complementarity, K-selection) to stabilize resource-efficient microbiomes-such as fecal microbiota transplantation and synthetic consortia, demonstrate further disease control potential. Our synthesis reveals that translating microbiome engineering from laboratory to farm requires overcoming host-microbiome compatibility challenges and ecological risks. Policy alignment with the United Nations Sustainable Development Goals-Zero Hunger (Sustainable Development Goal 2), Climate Action (Sustainable Development Goal 13), and Life Below Water (Sustainable Development Goal 14)-is critical for sustainable adoption.},
}

@article {pmid41035652,
year = {2025},
author = {Kalopedis, EA and Zorgani, A and Zinovkin, DA and Barri, M and Wood, CD and Pranjol, MZI},
title = {Leveraging the role of the microbiome in endometriosis: novel non-invasive and therapeutic approaches.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1631522},
pmid = {41035652},
issn = {1664-3224},
mesh = {Humans ; *Endometriosis/therapy/microbiology/immunology/diagnosis/metabolism/etiology ; Female ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/therapy/immunology/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Lactobacillus ; Biomarkers ; },
abstract = {Endometriosis (EMS) is an oestrogen-dependent condition characterised by ectopic endometrial-like tissue growth with a chronic and inflammatory nature leading to severe symptoms and reduced quality of life. Emerging evidence implicates gut microbiome dysbiosis in EMS pathogenesis, driving chronic inflammation, immune dysfunction, and altered bacterial taxa within patient gut microbiome. This review examines the intricate relationship between gut dysbiosis and EMS, with a focus on immunomodulatory mechanisms and the downstream consequences of the bacterial contamination theory. It evaluates recent findings regarding microbial imbalances and microbial diversity, pinpointing gaps in current research that mandate further understanding. For example, while microbial markers like Lactobacillus depletion and elevated Escherichia coli have been observed in patients, their diagnostic potential remains poorly defined. Additionally, it addresses the broader implications of EMS, including its physical, mental and healthcare burdens. Simultaneously, critiquing current drawbacks in diagnostic and therapeutic strategies such as their invasiveness and limited efficacy. The review further evaluates novel microbiome-based strategies namely Lactobacillus-based probiotics and faecal microbiota transplantation (FMT), assessing their potential in modulating immune responses and alleviating EMS symptoms while considering associated challenges. Lastly, it highlights the emerging role of metabolomics in identifying non-invasive and diagnostic biomarkers like short-chain fatty acids (SCFAs), implicated in the interplay between microbial metabolites and immune signalling pathways in EMS.},
}

Humans
*Endometriosis/therapy/microbiology/immunology/diagnosis/metabolism/etiology
Female
*Gastrointestinal Microbiome/immunology
Dysbiosis/therapy/immunology/microbiology
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Animals
Lactobacillus
Biomarkers

@article {pmid41035378,
year = {2025},
author = {Zhang, Q and Cui, J and Hou, Y and Guo, L and Li, H and Zhou, G and Wang, X and Zhu, B and Shi, K and Zhang, Y and Bi, Y and Li, Y and Sun, L and Feng, Y and Yuan, J and Wang, X},
title = {Alterations in Gut Microbiota and Metabolism in Cirrhotic Portal Hypertension: Implications for Disease Progression.},
journal = {Alimentary pharmacology & therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1111/apt.70392},
pmid = {41035378},
issn = {1365-2036},
support = {7232272//the Beijing Municipal Natural Science Foundation/ ; BJZYYB-2023-06//the Beijing Traditional Chinese Medicine Technology Development Fund Project/ ; 81774234//the National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Although gut microbiota has been implicated in various liver disorders, its relationship with cirrhotic portal hypertension (CPH) remains unclear.

AIMS: To investigate the structural and functional alterations of gut microbiota in patients with CPH and the potential role of these alterations in the progression of CPH.

METHODS: We collected faecal samples from 35 patients with CPH and 71 patients without CPH (controls) to conduct microbiome and metabolomic analyses. Gut microbes, faecal metabolites and their functional pathways associated with CPH were identified using multiple bioinformatics approaches. To understand the role of gut microbiota in the pathogenesis of CPH, we carried out faecal microbiota transplantation, CPH-characteristic bacterial transplantation and antibacterial experiments in mice.

RESULTS: Microbial diversity was diminished, and gut microbial structures were altered in patients with CPH compared to the controls, primarily manifested as increased abundance of lipopolysaccharide-producing bacteria and decreased abundance of anti-inflammatory bacteria. This dysbiosis of gut microbiota was accompanied by changes in the faecal metabolome, particularly in arginine biosynthesis and nitric oxide production. Transplantation of gut microbiota from CPH patients, as well as the transplantation of CPH-associated bacteria Veillonella nakazawae, was found to exacerbate CPH progression in mice. Antibiotic treatment significantly alleviated the CPH progression induced by N-dimethylnitrosamine in mice.

CONCLUSIONS: Our study reveals that gut microbiota dysbiosis is implicated in CPH progression, potentially providing new avenues for microbiome-based treatment for CPH.},
}

@article {pmid41035224,
year = {2025},
author = {Farini, A and Strati, F and Molinaro, M and Mostosi, D and Saccone, S and Tripodi, L and Troisi, J and Landolfi, A and Amoroso, C and Cassani, B and Blanco-Míguez, A and Leonetti, E and Bazzani, D and Bolzan, M and Fortunato, F and Caprioli, F and Facciotti, F and Torrente, Y},
title = {Immunoproteasome Inhibition Positively Impacts the Gut-Muscle Axis in Duchenne Muscular Dystrophy.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {16},
number = {5},
pages = {e70054},
doi = {10.1002/jcsm.70054},
pmid = {41035224},
issn = {2190-6009},
support = {M6/C2_CALL 2022//PNRR/ ; FRRB-2022//Unmet Medical Needs, Fondazione Regionale per la Ricerca Biomedica/ ; GJC21084//Cariplo Telethon Alliance GJC2021-2022/ ; //NextGenerationEU/ ; //MUR/ ; PR-0394//Gruppo familiari beta-sarcoglicanopatie/ ; PNC-E3-2022-23683266-CUP: C43C22001630001//Hub Life Science-Diagnostica Avanzata/ ; //Associazione Centro Dino Ferrari/ ; },
mesh = {Animals ; *Muscular Dystrophy, Duchenne/drug therapy/metabolism/pathology ; Mice ; Gastrointestinal Microbiome/drug effects ; *Proteasome Inhibitors/pharmacology/therapeutic use ; *Muscle, Skeletal/drug effects/metabolism ; Disease Models, Animal ; Mice, Inbred mdx ; Male ; *Proteasome Endopeptidase Complex/metabolism ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Duchenne Muscular Dystrophy (DMD) features immune-muscle crosstalk, where muscle fibre degeneration enhances pro-inflammatory macrophage infiltration, worsening inflammation and impairing regeneration.

METHODS: We investigated the impact of immunoproteasome (IP) inhibition on the gut-muscle axis in mdx mice, a well-established model of DMD. We employed microbiota perturbation models, including broad-spectrum antibiotic treatment (ABX) and faecal microbiota transplantation (FMT) from IP-inhibited mdx mice. IP inhibition effects were assessed by analysing gut microbiota composition, intestinal inflammation, muscle integrity and associated metabolic and inflammatory pathways.

RESULTS: IP inhibitor ONX-0914 significantly impacted the intestinal inflammatory microenvironment and gut microbiota of mdx mice. ONX-0914 treatment increased gastrointestinal transit (increased wet/dry faecal weights, p = 0.0486 and p = 0.0112, respectively) and partially restored intestinal barrier integrity (reduced FITC-dextran leakage, p = 0.0449). JAM-A was significantly upregulated (p < 0.0001). Colonic CD206+ M2 macrophages increased, while CD68 + M1 cells partially decreased. ONX-0914 downregulated IP isoforms in macrophages (PSMB8: p = 0.0022; PSMB9: p = 0.0186) as well as FOXO-1 (p = 0.0380) and TNF-α (p = 0.0487). Antibiotic-induced microbiota depletion abrogated these effects. Metagenomic analysis revealed significant differences in microbiota composition between C57Bl controls and mdx mice (PERMANOVA p < 0.001), with ONX-0914 inducing enrichment of stachyose degradation pathways. Metabolomic analysis showed enrichment of bacterial metabolites, fatty acid and sugar metabolism pathways, with increased glutathione, galactose, glycerol, glyceraldehyde and TCA cycle intermediates. ONX-0914 improved mitochondrial activity in skeletal muscle, as increased expression of ETC complexes (mdx vs. mdx+ONX: Complex II, p = 0.0338; Complex IV, p = 0.0023) and TCA enzymes (mdx vs. FTMmdx+ONX: IDH p = 0.0258; FH p = 0.0366). This led to a shift towards oxidative muscle fibres and improved muscle morphology (increased fibre size, p < 0.0001 mdx vs. mdx+ONX and mdx vs. FTMmdx+ONX). Muscle performance was enhanced with reduced CPK levels (p = 0.0015 mdx vs. mdx+ONX) and fibrosis (decreased TGFβ: mdx vs. mdx+ONX, p = 0.0248; mdx vs. FTMmdx+ONX, p = 0.0279). ONX-0914 reduced CD68+ (mdx vs. mdx+ONX, p = 0.0024; mdx vs. FTMmdx+ONX, p < 0.0001) and increased CD206+ (mdx vs. FTMmdx+ONX: p = 0.0083) macrophages in muscle, downregulated inflammatory genes (mdx vs. mdx+ONX: ccl2 p = 0.0327, vcam-1p = 0.0378) and reduced pro-inflammatory proteins (MCP1, mdx vs. mdx+ONX, p = 0.0442). Inflammatory cytokines and endothelial vessel density in ONX-0914 treated mdx were restored to wild type mice. These data demonstrate that ONX-0914 enhances muscle function through microbiota-dependent mechanisms.

CONCLUSIONS: Our study advances the understanding of the role of dysbiosis in DMD disease and identifies IP inhibition as a potential therapeutic strategy to modulate the dystrophic gut-muscle axis, offering new perspectives for microbiota-targeted therapies.},
}

Animals
*Muscular Dystrophy, Duchenne/drug therapy/metabolism/pathology
Mice
Gastrointestinal Microbiome/drug effects
*Proteasome Inhibitors/pharmacology/therapeutic use
*Muscle, Skeletal/drug effects/metabolism
Disease Models, Animal
Mice, Inbred mdx
Male
*Proteasome Endopeptidase Complex/metabolism
Mice, Inbred C57BL

@article {pmid41033875,
year = {2025},
author = {Kopple, JD and Bross, R and Ekramzadeh, M and Markovic, D and Lyzlov, A and Lodebo, BT and Mehrotra, R and Shah, AP},
title = {Lanthanum carbonate lowers serum phosphorus without altering body phosphorus burden in maintenance peritoneal dialysis patients: a randomized crossover trial.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.08.015},
pmid = {41033875},
issn = {1938-3207},
abstract = {BACKGROUND: Many studies show that intestinal phosphate binders reduce serum phosphorus concentrations in hyperphosphatemic patients with chronic kidney failure. To our knowledge, there are virtually no studies of the effect of these binders on fecal phosphate or body phosphate.

OBJECTIVES: This study examined the hypothesis that phosphate binders increase fecal phosphate and reduce body phosphorus burden.

METHODS: Seven adult patients undergoing maintenance peritoneal dialysis underwent full metabolic balance studies for phosphorus in a research ward while they ate a constant phosphorus diet. Patients were studied during a baseline period without phosphate binders and while they received, in random order, 3 doses of lanthanum carbonate (La2(CO3)3), 1.5, 3.0, and 4.5 g/d, in 3 divided daily doses for ∼12-14 d each. The total duration of study was 47-49 d in each patient. Dialysate, urine, and feces were collected continuously and serum intermittently for phosphorus measurements.

RESULTS: Serum phosphorus concentrations fell progressively and significantly as the La2(CO3)3 dose was increased (r = -0.47, P < 0.001). Fecal phosphorus concentrations rose progressively as La2(CO3)3 increased (r = 46.4, P < 0.001). However, there was a negative correlation between both dialysate (r = -17.2, P = 0.002) and urine (r = -18.5, P < 0.001) phosphorus and La2(CO3)3 dose. This decline in dialysate and urine phosphorus correlated with the fall in serum phosphorus concentration as the La2(CO3)3 dose increased. As the La2(CO3)3 dose rose, the increase in fecal phosphorus concentration was essentially counterbalanced by the fall in dialysate and urine phosphorus. Hence, body phosphorus balance did not change with increasing La2(CO3)3 doses.

CONCLUSIONS: La2(CO3)3 treatment lowered serum phosphorus concentration but did not change body phosphorus content. This trial was registered at clinicaltrials.gov as NCT01581996.},
}

@article {pmid41033511,
year = {2025},
author = {Bian, S and Zhu, S and Lu, J and Iqbal, M and Jamil, T and Kiani, FA and Dong, H and Dai, H and Zhang, X and Liu, F and Li, A},
title = {Targeting gut microbiota in non-alcoholic fatty liver disease (NAFLD): Pathogenesis and therapeutic insights: A review.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {147995},
doi = {10.1016/j.ijbiomac.2025.147995},
pmid = {41033511},
issn = {1879-0003},
abstract = {Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by hepatic steatosis associated with insulin resistance, oxidative stress, inflammatory responses, and other factors. The precise pathogenesis of NAFLD remains unclear. Although it has emerged as a global health burden, current therapeutic options for example, probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT) have shown promising but varied efficacy. Moreover, use of traditional Chinese medicine (TCM) in NAFLD patients, has gained growing attention for its multi-targeted regulatory properties and several natural product formulations and their beneficial impacts on gut microbiota, lipid metabolism and hepatic health. The article highlights the role of gut microbiota dysbiosis in the pathogenesis of NAFLD and explores the therapeutic strategies emphasizing the need of personalized multimodal approaches and robust clinical trials to validate these interventions.},
}

@article {pmid41032750,
year = {2025},
author = {Gurer Kluge, EE and Meedt, E and Feicht, J and Cao, K and Hiergeist, A and Mamilos, A and Hirsch, D and Hoepting, M and Kattner, AS and Matos, C and Bülow, S and Thiele Orberg, E and Beckhove, P and Kandulski, A and Evert, M and Hildner, K and Kreutz, M and Edinger, M and Wolff, D and Herr, W and Poeck, H and Gessner, A and Weber, DA and Kehr, B and Holler, E and Ghimire, S},
title = {Mucosal calprotectin is associated with severity of aGI-GVHD and poor outcomes after allogeneic stem cell transplantation.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025029402},
pmid = {41032750},
issn = {1528-0020},
abstract = {Calprotectin, a calcium- and zinc-binding protein composed of the subunits S100A8 and S100A9, has been extensively studied as a biomarker of gastrointestinal (GI) inflammation through fecal and serum analyses. However, its role in intestinal tissue remains poorly understood due to limited availability of biopsies. In this study, we analyzed S100A8 and S100A9 mRNA expression in 579 intestinal biopsies from allogeneic stem cell transplant (ASCT) patients and observed a strong association with acute GI graft-versus-host disease (aGI-GvHD) (p<0.001). Neutrophil infiltration correlated with the severity of aGI-GvHD (p<0.001), and calprotectin expression was strongly linked to Toll-like receptor 4 (TLR4) (p<0.001) and TLR2 (p<0.001) expression. TLR4 and aGI-GvHD were associated with elevated calprotectin mRNA levels (p<0.001). When patients received broad-spectrum antibiotics at disease onset, expression of calprotectin was suppressed (S100A8, p=0.001; S100A9, p=0.01). Gastrointestinal site-specific differences in calprotectin expression were identified: during severe aGI-GvHD, levels increased up to 30-fold in the small intestine and up to 5-fold in the large intestine with respect to mild/no aGI-GVHD, while under homeostasis, the large intestine exhibited higher baseline calprotectin (p=0.001). The high clinical relevance is evident from the observation that calprotectin expression was prognostic for transplant-related mortality (TRM). Our study suggests that (a) calprotectin is a potential biopsy biomarker in aGI-GvHD, (b) calprotectin expression and neutrophil infiltration possibly indicate translocation of microbiota, which (c) may be modulated by antibiotics.},
}

@article {pmid41031618,
year = {2025},
author = {Xu, F and Yue, Y and Sun, D},
title = {Mechanism of the AMPK/SIRT1 pathway in gut dysbiosis-mediated postoperative cognitive dysfunction in aged mice.},
journal = {The international journal of neuropsychopharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1093/ijnp/pyaf066},
pmid = {41031618},
issn = {1469-5111},
abstract = {OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a prevalent complication in older patients who undergo surgery that requires anesthesia. This study explored the role of the AMPK/SIRT1 pathway in gut dysbiosis-mediated POCD in aged mice.

METHODS: POCD was induced in aged male mice via open tibial fracture surgery under isoflurane anesthesia. Mice then received the probiotic VSL#3, the SIRT1 inhibitor EX527, and the AMPK/SIRT1 activator resveratrol. Fecal microbiota transplantation was conducted in aged POCD mice. Mouse cognitive function was assessed using the Morris water maze and novel object recognition tests. Mouse histopathological changes were observed via HE staining. Iba1+/GFAP+ activation was assessed via immunofluorescence, and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 [IL]-1β, IL-6) in the hippocampus were determined via ELISA. Gut microbiota compositions were detected via 16S rRNA sequencing. Hippocampal pAMPK/AMPK and SIRT1 levels were assessed by western blot.

RESULTS: Aged POCD mice exhibited prolonged escape latency, reduced platform crossings, and an impaired object discrimination rate on postoperative day 7. Severe hippocampal CA1 damage, increased Iba1+/GFAP+ cell numbers, elevated pro-inflammatory cytokines, and gut dysbiosis were also observed. The probiotic VSL#3 ameliorated gut dysbiosis, alleviated POCD, and reduced neuroinflammation. Gut microbiota from POCD mice exacerbated cognitive deficits and neuroinflammation in aged mice, while clearance of gut microbiota improved outcomes. VSL#3 improved POCD in aged mice by balancing gut microbiota through the AMPK/SIRT1 pathway. The AMPK/SIRT1 pathway activation mitigated POCD.

CONCLUSION: VSL#3 balanced gut microbiota and suppressed neuroinflammation in hippocampal CA1 region by activating the AMPK/SIRT1 pathway, thereby alleviating POCD in aged mice.},
}

@article {pmid41030553,
year = {2025},
author = {Xie, H and Zhu, S and Xue, P and Xie, F and Zhao, L and Chu, X},
title = {Yanggan Yizhong decoction prevents liver metastasis from colorectal cancer by targeting myeloid-derived suppressor cells through the regulation of bile acid metabolism in the gut microbiota.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1639442},
pmid = {41030553},
issn = {1664-302X},
abstract = {INTRODUCTION: Liver metastasis (LM) exhibits a high incidence in colorectal cancer (CRC), yet effective preventive therapies are still lacking. Based on the prophylactic principle of harmonizing the liver and spleen, Yanggan Yizhong (YGYZ) decoction has shown clinical effectiveness in preventing LM. This study aims to explore the active components and underlying mechanisms of YGYZ in the prevention and treatment of LM.

METHODS: The components of YGYZ were analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Tandem Mass Spectrometry (UPLC-HR-MS/MS). The LM mouse model was established through intrasplenic injection of ct26-luc cells to evaluate the effect and safety of YGYZ on LM. Fecal microbiota transplantation (FMT) was performed to create microbiota-altered mice, and liver tissue morphology along with HE staining was utilized to dynamically monitor LM progression. Flow cytometry and inflammatory factor assays were conducted to assess the immune microenvironment (IME) of the liver pre-metastatic niche (PMN). Additionally, 16S rRNA sequencing and bile acid (BA) metabolomics were employed to investigate the role of YGYZ in modulating gut microbiota (GM) and BA. Western blot analysis was performed to identify key targets of YGYZ in the GM-BA-immunity pathway.

RESULTS: UPLC-HR-MS/MS analysis identified 95 compounds in YGYZ, Glycyrrhizic acid, Bergapten, and Icariin as the main compounds. YGYZ and its FMT inhibited LM of CRC with safety, inhibited CD11b+Ly6G+ and CD11b+Ly6C+ cells in the pre-metastatic stage, decreased CD11b+Ly6G+ cells in the metastatic stage, reduced immunosuppressive factors such as Arg-1, TGF-β, and IL-10, and improved the CD4+/CD8+ T-cell ratio, regulating liver PMN. YGYZ also improved the GM structure, particularly decreasing the abundance of Clostridium in the LM mice. For the hepatic BAs profile, YGYZ increased the content of primary BAs-Nor cholic acid (NorCA), Taurocholic acid, Taurochenodeoxycholic Acid, and Tauro β-Muricholic Acid, and secondary BAs-ursodeoxycholic acid (UDCA), with similar trends in FMT, while YGYZ decreased NorCA, α-Muricholic acid, Tauro α-Muricholic acid, and UDCA in the fecal BA profile. YGYZ and its FMT dampened the protein expression of IL-6, STAT3, and pSTAT3, but only YGYZ downregulated kruppel-like factor 15 (KLF15).

CONCLUSION: YGYZ may prevent LM by remodeling the GM and synergistically inhibiting KLF15 to regulate the enterohepatic BA cycle, and suppressing the proliferation and activation of myeloid-derived suppressor cells through the IL-6/STAT3 pathway, thereby improving IME of liver PMN.},
}

@article {pmid41030253,
year = {2025},
author = {Bautista, J and Villegas-Chávez, JA and Bunces-Larco, D and Martín-Aguilera, R and López-Cortés, A},
title = {The microbiome as a therapeutic co-driver in melanoma immuno-oncology.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1673880},
pmid = {41030253},
issn = {2296-858X},
abstract = {Melanoma, one of the most aggressive skin cancers, remains a major clinical challenge due to its high metastatic potential, therapy resistance, and rising global incidence. Although immune checkpoint inhibitors have transformed management, variable responses and acquired resistance limit durable benefit. Emerging evidence positions the microbiome as a pivotal determinant of melanoma biology and therapeutic outcomes. Dysbiosis in the skin, gut, and oral compartments fosters tumor-promoting inflammation, immune evasion, and oncogenic signaling, whereas enrichment of specific commensals, such as Akkermansia muciniphila and Faecalibacterium prausnitzii, enhances antigen presentation and effector T cell activity, improving ICI efficacy. Mechanistically, microbial metabolites, including short-chain fatty acids, tryptophan derivatives, and bile acids, modulate epigenetic programs, G-protein-coupled receptor signaling, and oncogenic cascades such as PI3K-AKT and RAS-RAF-MEK-ERK. Beyond the gut, cutaneous microbiota such as Staphylococcus epidermidis exert direct antitumor effects, while pathogenic oral taxa propagate systemic inflammation that shapes the melanoma tumor microenvironment. These insights are driving the development of microbiome-targeted interventions, including fecal microbiota transplantation, defined consortia, probiotics, and dietary modulation, with early clinical studies showing the potential to overcome resistance to immunotherapy. Integration of circadian biology further suggests that host-microbiome-immune interactions are temporally regulated, opening new dimensions for therapeutic optimization. By synthesizing mechanistic, clinical, and translational advances, this review highlights the microbiome as both a biomarker and a therapeutic axis in melanoma, underscoring its promise to transform precision immuno-oncology.},
}