@article {pmid42902422,
year = {2026},
author = {Gao, H and Gu, J and Wang, Y and Zou, Y and Wang, Z and Fang, R and Jiang, S},
title = {Heat stress triggers bone performance degeneration via impairing intestinal barrier function and altering gut microbiota in chickens.},
journal = {Animal microbiome},
volume = {8},
number = {1},
pages = {},
pmid = {42902422},
issn = {2524-4671},
support = {32402955//National Natural Science Foundation of China/ ; SWU-KQ24004//Fundamental Research Funds for the Central Universities/ ; 202405AF140106//the Yunnan Province Science and Technology Talents and Platform Program/ ; },
abstract = {Heat stress (HS) is a pervasive environmental hazard in intensive poultry production that severely impairs skeletal health and causes substantial economic losses. While emerging evidence links gut microbiota dysbiosis to bone metabolism, its causal role in mediating HS-induced bone loss remains poorly defined. Here, we established a chicken model of HS and employed fecal microbiota transplantation (FMT) to investigate the mechanistic link between gut microbiota and skeletal deterioration. Our results demonstrated that HS reduced growth performance, disrupted gut microbial community structure, and impaired bone microarchitecture and biomechanical strength. Critically, FMT from HS-exposed donors recapitulated the key features of HS-induced bone loss in recipient chickens, characterized by impaired trabecular bone microarchitecture, reduced biomechanical strength, and enhanced bone resorption-related gene expression. Mechanistically, the HS-microbiota induces functional dysbiosis, characterized by a relative increase in the abundance of the genus Turicibacter, while compromising intestinal barrier integrity, triggering an inflammatory response, and inhibiting intestinal mineral absorption. Collectively, these factors contribute to reduced bone performance. These findings establish the gut microbiota as a key mediator of HS-induced bone loss, providing a novel mechanistic framework for understanding host-microbiota-environment interactions in the context of environmental hazards, which has broader implications for animal health and environmental toxicology.},
}

@article {pmid42903521,
year = {2026},
author = {Chen, K and Li, Q and Xing, Y and Liu, C and Yang, F},
title = {Gut microbiota dysbiosis in pediatric acute lymphoblastic leukemia: clinical consequences, mechanistic insights, and microbiota-targeted interventions.},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1928304},
pmid = {42903521},
issn = {2296-2360},
abstract = {Gut microbiota dysbiosis has emerged as a key feature in pediatric acute lymphoblastic leukemia (ALL), driven by chemotherapy, antibiotic exposure, and treatment-related nutritional impairment. Increasing evidence indicates that disruption of microbial diversity and depletion of short-chain fatty acid-producing bacteria are closely associated with infectious complications, gastrointestinal toxicity, and potentially reduced treatment efficacy. This review synthesizes current evidence on the interplay between gut microbiota and pediatric ALL across four dimensions: clinical outcomes, treatment-related toxicity, pharmacological interactions, and prognosis. We further summarize how leukemia therapy reshapes microbial ecosystems through cytotoxic agents, antimicrobial exposure, and dietary alterations. In addition, we discuss microbiota-centered therapeutic strategies, including probiotics, prebiotics, synbiotics, postbiotics, dietary interventions, and fecal microbiota transplantation. While promising, these approaches require careful validation in pediatric oncology due to safety considerations and limited clinical trial data. Finally, we highlight methodological advances such as multi-omics integration and machine learning approaches, which may enable microbiome-based risk stratification and precision supportive care in the future. Overall, gut microbiota represents a potential modifiable factor influencing clinical outcomes in pediatric ALL.},
}

@article {pmid42903564,
year = {2023},
author = {Yan, H and Ren, J and Liu, GH},
title = {Fecal microbiota transplantation: A new strategy to delay aging.},
journal = {hLife},
volume = {1},
number = {1},
pages = {8-11},
pmid = {42903564},
issn = {2949-9283},
abstract = {The gut microbiota, the community of gut microorganisms that inhabit the gastrointestinal tract, plays a crucial role in modulating host immunity, metabolism, and neurological health, thereby influencing the entire organism. Aging is associated with changes in gut microbiota composition and functionality, often resulting in dysbiosis, an imbalance of gut microbiota and an aging hallmark. Recent studies have suggested that fecal microbiota transplantation (FMT), the transfer of fecal material containing beneficial microbes from a healthy donor to a recipient with a disturbed microbiota, may restore the balance of host gut microbiota and ameliorate some aging-associated impairments in diverse organs. In particular, FMT from young donors has shown more beneficial effects than FMT from aged donors. In this paper, we review recent advances in FMT for its effects on aging and discuss the potential mechanisms and challenges of this novel intervention, highlighting its potential to improve health outcomes in the aging population.},
}

@article {pmid42903936,
year = {2026},
author = {Wang, S and Huai, S and Yuan, Z and Ji, T and Xu, Y and Ren, Y and Qian, N and Sun, S and Li, J},
title = {Berberine alleviates radiation-induced lung injury by promoting microbiota-derived inosine via the gut-lung axis.},
journal = {hLife},
volume = {4},
number = {3},
pages = {165-185},
pmid = {42903936},
issn = {2949-9283},
abstract = {Radiation-induced lung injury (RILI) is a common complication of radiotherapy. Although berberine (BBR) has been suggested to be associated with reduced RILI incidence, the underlying mechanisms remain unknown. Here, we investigated whether the gut microbiota mediates the radioprotective effects of BBR using a C57BL/6 RILI mouse model with 20 Gy thoracic irradiation (n = 6 per group). BBR (100 mg/kg) and inosine (INO, 300 mg/kg) were administered orally in vivo. Antibiotic depletion and fecal microbiota transplantation were performed to assess microbiota dependence. Lung injury was assessed by histology, pulmonary function, and cytokine levels. Gut microbiota was analyzed by 16S rRNA sequencing, and metabolites were profiled using LC-MS/MS. Transcriptomic and epigenomic alterations were assessed by RNA sequencing, ATAC sequencing, and CUT&Tag analysis. Molecular docking and surface plasmon resonance were used to assess metabolite-protein interactions. We demonstrated that BBR alleviated RILI in a microbiota-dependent manner. BBR increased Akkermansia muciniphila abundance and metabolite INO levels. Mechanistically, INO was associated with reduced neuron navigator 3 (NAV3) expression, accompanied by decreased chromatin accessibility and increased histone H3 lysine 27 trimethylation (H3K27me3) at the NAV3 locus. Together, these findings reveal a gut microbiota-mediated mechanism underlying BBR-mediated protection against RILI, and suggest microbiota-informed biomarkers for risk stratification.},
}

@article {pmid42903958,
year = {2024},
author = {Tian, H and Wang, X and Fang, Z and Li, L and Wu, C and Bi, D and Li, N and Chen, Q and Qin, H},
title = {Fecal microbiota transplantation in clinical practice: Present controversies and future prospects.},
journal = {hLife},
volume = {2},
number = {6},
pages = {269-283},
pmid = {42903958},
issn = {2949-9283},
abstract = {The gut microbiota, serving as the only "organ" that humans can share, has been extensively applied in the treatment of various intestinal and extraintestinal diseases through fecal microbiota transplantation (FMT) technology. By optimizing the donor selection strategy, FMT exhibited the highest effectiveness (more than 90%) in treating acute intestinal inflammations, such as recurrent Clostridium difficile infection. However, the efficacy diminishes when addressing intestinal functional diseases (more than 60%), chronic intestinal inflammations or organic diseases (less than 60%), and extraintestinal diseases, particularly those lacking any gastrointestinal symptoms (less than 50%). Ongoing efforts to enhance the therapeutic response of FMT across diverse diseases represent a central focus of current clinical research. This review concentrates on donor selection, recipient management, precise donor-recipient matching, antagonistic mechanism of native bacteria to transplanted bacteria, and targeted treatment strategies for different diseases, with the aim of providing practical strategies to improve the clinical efficacy of FMT.},
}

@article {pmid42903976,
year = {2025},
author = {Wang, Y and Yan, H and Zheng, Q and Sun, X},
title = {Crucial functions of gut microbiota on gut-liver repair.},
journal = {hLife},
volume = {3},
number = {8},
pages = {364-385},
pmid = {42903976},
issn = {2949-9283},
abstract = {The gut microbiota exert a critical influence on the gut-liver axis by facilitating intestinal and hepatic repair via intricate bidirectional mechanisms. Inflammatory bowel disease (IBD), metabolic-associated steatohepatitis (MASH), and the gut-liver axis exemplify the complex interplay between the gut microbiota and hepatic function. This review explores the interplay between microbial metabolites and their roles in maintaining intestinal integrity and promoting liver regeneration. Emerging evidence shows that gut microbiota support intestinal and liver health by modulating immune responses via microbial metabolites and interactions with host immune cells. Moreover, advances in personalized therapies, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), could potentially restore microbial balance and enhance tissue repair. Understanding these relationships presents opportunities for innovative interventions to improve gut and liver health, particularly in individuals with metabolic disorders.},
}

@article {pmid42905002,
year = {2026},
author = {Chu, Z and Zhang, X and Zhu, B and Liu, Q and Zeng, Y and Zhou, Y and Hu, Z and Luo, F},
title = {Protective Effects of Narirutin Against Exercise-Induced Fatigue in Mice: Insights from Integrated Microbiome, Metabolome, and Transcriptome Analysis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {41},
pages = {32426-32447},
doi = {10.1021/acs.jafc.6c11203},
pmid = {42905002},
issn = {1520-5118},
support = {25B0319//Education Department of Hunan Province/ ; 32603353//National Natural Science Foundation of China/ ; 2022YFF1100200//National Key Research and Development Program of China/ ; 2024YJ006//Central South University of Forestry and Technology/ ; 2025QT-40//Hunan Province 2025 Furong Plan Youth Talent Project/ ; },
mesh = {Animals ; Mice ; *Fatigue/microbiology/metabolism/drug therapy/genetics/etiology/prevention & control ; Male ; *Gastrointestinal Microbiome/drug effects ; Metabolome/drug effects ; Physical Conditioning, Animal/adverse effects ; Humans ; Multiomics ; Bacteria/genetics/isolation & purification/classification/drug effects/metabolism ; Mice, Inbred C57BL ; Transcriptome/drug effects ; *Protective Agents/administration & dosage ; Gene Expression Profiling ; },
abstract = {Exercise-induced fatigue is linked to oxidative stress, inflammation and intestinal dysbiosis. Narirutin (NAR), a natural flavonoid, lacks systematic evidence and mechanistic clarification against exercise fatigue. Herein, a forced exercise fatigue mouse model was constructed, and behavioral, biochemical, histological and multiomics analyses including 16S rRNA sequencing, untargeted metabolomics, transcriptomics and RT-qPCR were performed. Fecal microbiota transplantation (FMT) and antibiotic-mediated microbiota depletion further verified the causal role of gut microbiota. NAR dose-dependently improved exercise endurance, muscle strength, glycogen storage, oxidative status and inflammatory profiles. It restored gut microbial diversity, remodelled microbial composition and altered metabolic signatures. Multiomics integration indicated NAR regulated immune genes via the gut microbiota-metabolite-gene axis. FMT reproduced antifatigue effects, whereas antibiotic treatment eliminated NAR protection. This study demonstrates that NAR alleviates exercise-induced fatigue largely relying on intact gut microbiota, although microbiota-independent peripheral effects cannot be fully excluded. These findings support its exploitation as a natural antifatigue functional component.},
}

Animals
Mice
*Fatigue/microbiology/metabolism/drug therapy/genetics/etiology/prevention & control
Male
*Gastrointestinal Microbiome/drug effects
Metabolome/drug effects
Physical Conditioning, Animal/adverse effects
Humans
Multiomics
Bacteria/genetics/isolation & purification/classification/drug effects/metabolism
Mice, Inbred C57BL
Transcriptome/drug effects
*Protective Agents/administration & dosage
Gene Expression Profiling

@article {pmid42905003,
year = {2026},
author = {Wang, Z and Lu, Y and Zhao, Y and Li, H and Liao, X and Li, J and Huang, J and Wang, K and Liu, Z and Zhu, M},
title = {Dihydromyricetin Alleviates Reserpine-Induced Depression by Modulating the Microbiota-Gut-Brain Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {41},
pages = {32288-32308},
doi = {10.1021/acs.jafc.6c05330},
pmid = {42905003},
issn = {1520-5118},
support = {20B282//Education Department of Hunan Province/ ; 32172217//National Natural Science Foundation of China/ ; 32472797//National Natural Science Foundation of China/ ; 2022RC1142//Department of Science and Technology of Hunan Province/ ; 2023JJ50004//Natural Science Foundation of Hunan Province/ ; 2025JJ20022//Natural Science Foundation of Hunan Province/ ; 25KJ025//Hunan Agricultural University/ ; 2022YFD2101103//National Key Research and Development Program of China/ ; 2024JK2150//Key Research and Development Program of Hunan Province of China/ ; },
mesh = {Animals ; *Depression/drug therapy/microbiology/metabolism/chemically induced/psychology ; *Flavonols/administration & dosage ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Brain/drug effects/metabolism ; Male ; Reserpine/adverse effects ; Humans ; Rats, Sprague-Dawley ; *Antidepressive Agents/administration & dosage ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Bacteria/isolation & purification/classification/genetics/drug effects/metabolism ; },
abstract = {Dihydromyricetin (DMY) is a natural flavonoid with neuroprotective and antidepressant potential, but its role in the microbiota-gut-brain axis remains unclear. Using a reserpine-induced depression rat model, we integrated behavioral, inflammatory, histological, microbiota, metabolomic, and fecal microbiota transplantation (FMT) analyses. DMY alleviated anhedonia, behavioral despair, and cognitive dysfunction, reduced circulating pro-inflammatory cytokines and hippocampal neuronal damage, and increased brain-derived neurotrophic factor expression. DMY also restored gut microbial diversity and composition and partially normalized bile acid and short-chain fatty acid profiles. Notably, FMT from DMY-treated donors reproduced antidepressant-like behavioral effects and restored key microbial metabolites. These findings suggest that DMY may alleviate depression-like phenotypes through coordinated regulation of gut microbiota, microbial metabolites, and neuroinflammatory responses, supporting its potential as a dietary strategy for depression management.},
}

Animals
*Depression/drug therapy/microbiology/metabolism/chemically induced/psychology
*Flavonols/administration & dosage
Rats
*Gastrointestinal Microbiome/drug effects
*Brain/drug effects/metabolism
Male
Reserpine/adverse effects
Humans
Rats, Sprague-Dawley
*Antidepressive Agents/administration & dosage
Brain-Derived Neurotrophic Factor/genetics/metabolism
Bacteria/isolation & purification/classification/genetics/drug effects/metabolism

@article {pmid42906799,
year = {2026},
author = {Huo, W and Hou, X and Huang, Y and Li, Z and Chen, X and Feng, J and Kong, Y and Pan, S and Wang, Q and Xu, J and Chen, J and Li, J and Yang, R and Lu, Y and Liu, Y},
title = {Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122520},
doi = {10.1016/j.jep.2026.122520},
pmid = {42906799},
issn = {1872-7573},
abstract = {Sepsis-associated acute lung injury (SA-ALI) has high mortality and limited therapies.Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.

AIM OF THE STUDY: To evaluate the protective effects of THCQ pretreatment against LPS-induced SA-ALI and examine associated changes in gut microbiota, succinate levels, SUCNR1-PKA-CREB signaling and macrophage polarization.

MATERIALS AND METHODS: A murine SA-ALI model was induced by intraperitoneal LPS. Lung injury, inflammatory cytokines (IL-1β, TNF-α), and M1/M2 polarization were assessed. Gut microbiota was analyzed by 16S rRNA sequencing. Succinate levels, SUCNR1, and PKA-CREB signaling were measured. Microbiota dependence was tested using antibiotic depletion, fecal microbiota transplantation (FMT) from THCQ-treated donors, exogenous succinate, and macrophage depletion with clodronate liposomes.

RESULTS: THCQ pretreatment attenuated lung injury, reduced IL-1β and TNF-α levels, and shifted pulmonary macrophage polarization toward an M2-like phenotype. These effects were accompanied by altered gut microbiota composition, a lower abundance ratio of bacterial families grouped in the exploratory succinate-metabolism analysis, reduced serum and pulmonary succinate levels, lower SUCNR1 expression, and increased PKA/CREB phosphorylation. Antibiotic treatment attenuated the protective responses to THCQ, while FMT from THCQ-treated donors reproduced improvements in lung injury. Exogenous succinate attenuated THCQ-mediated protection. Clo-Lipo treatment reduced the proportions of alveolar and interstitial macrophages and markedly attenuated the protective effects of THCQ.

CONCLUSION: THCQ treatment protects against SA-ALI and suppresses M1-like macrophage polarization. These effects are accompanied by changes in gut microbiota composition, reduced succinate levels, and altered SUCNR1-PKA-CREB signaling. Together, the findings support a role for gut microbiota-metabolism-immune interactions in the protective effects of THCQ.},
}

@article {pmid42901457,
year = {2026},
author = {Zuo, Y and Li, Y and Huang, Z and Zeng, H and Liu, Q and Zhou, Y and Chen, X and Chen, W and Wang, K and Chen, Q},
title = {Yupingfeng alleviates allergic rhinitis by modulating gut microbiota and succinate to inhibit mTOR/S6K signaling.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122558},
doi = {10.1016/j.jep.2026.122558},
pmid = {42901457},
issn = {1872-7573},
abstract = {Yupingfeng granules (YPF), derived from the classic traditional Chinese medicine prescription Yupingfeng powder, have been recommended in clinical practice guidelines for the management of allergic rhinitis (AR), and their clinical efficacy is widely recognized. However, the underlying pharmacological mechanisms have not been thoroughly investigated.

AIM OF THE STUDY: This study aimed to investigate whether YPF protects the nasal epithelial barrier and alleviates AR by modulating the gut microbiota and pathways related to its metabolites.

MATERIALS AND METHODS: An OVA-induced AR mouse model was established and phenotypically evaluated. The dependence of YPF efficacy on gut microbiota was assessed by 16S rRNA sequencing, antibiotic depletion, and fecal microbiota transplantation. [1]H-NMR metabolomics was used to identify key metabolites, followed by exogenous supplementation for validation. Nasal mucosal transcriptome sequencing was performed to explore downstream pathways, and functional validation was conducted in OVA-induced HNEpCs through metabolite intervention, YPF co-treatment, mTOR knockdown, and MHY1485 treatment.

RESULTS: YPF dose-dependently reduced nasal rubbing and sneezing, attenuated IgE-mediated type 2 inflammation, and ameliorated nasal epithelial barrier injury in OVA-induced AR mice. YPF remodeled the gut microbiota and increased microbial diversity. Gut microbiota depletion attenuated the protective effects of YPF, whereas FMT from YPF donors reproduced them. Metabolomic analysis identified succinate as a key YPF-responsive metabolite, and exogenous succinate aggravated nasal epithelial barrier injury. Transcriptomic analysis suggested that succinate-induced nasal mucosal injury may involve mTOR signaling activation. In vitro, succinate aggravated OVA-induced barrier injury in HNEpCs, with disrupted Occludin distribution and enhanced mTOR/S6K phosphorylation, whereas YPF co-treatment reversed these changes. mTOR knockdown mimicked the protective effects of YPF, whereas MHY1485 attenuated them.

CONCLUSION: YPF alleviates OVA-induced AR by remodeling the gut microbiota, reducing succinate accumulation, and suppressing mTOR/S6K signaling to preserve nasal epithelial barrier integrity.},
}

@article {pmid42902271,
year = {2026},
author = {Asna Ashari, K and MacRae, R and Hoytema van Konijnenburg, DP and Platt, CD and Ashoor, M and See, AP and Kielian, A and Danehy, A and Kumar, R and James, E and Houghton, K and Harder, S and Gorman, MP and Kahn, SA and Daga, A and Hussain, SH and Johnston, AM and Casey, A and Ouahed, JD and Wong, W and Jenkins, K and Prockop, S and Eloseily, E and Risma, K and Ombrello, MJ and Dedeoglu, F and Andzelm, MM},
title = {Neurological manifestations and vasculopathy in PLCG2-associated antibody deficiency and immune dysregulation (APLAID): a case series.},
journal = {Pediatric rheumatology online journal},
volume = {24},
number = {1},
pages = {},
pmid = {42902271},
issn = {1546-0096},
mesh = {Humans ; Female ; *Phospholipase C gamma/genetics ; Infant ; Male ; Magnetic Resonance Imaging ; *Immunologic Deficiency Syndromes/genetics/complications ; Magnetic Resonance Angiography ; },
abstract = {BACKGROUND: Autosomal dominant pathogenic variants in PLCG2 are associated with autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID), characterized by immunological abnormalities and multi-system inflammation. Descriptions of associated neurological manifestations and vascular anomalies are limited. We describe three patients with APLAID, vasculopathies, neuroinflammation, and cerebral vascular tortuosity. These cases highlight underrecognized and clinically important manifestations of APLAID.

CASE PRESENTATIONS: All three patients had de novo variants in PLCG2 and early systemic inflammatory and immunodeficiency findings within the spectrum of APLAID (e.g. immune laboratory abnormalities, skin and gastrointestinal inflammation, and frequent infections). Additionally, they had notable neurological and vascular findings. Patient #1 (PLCG2 c.3420T > A; p.Asp1140Glu) is a female who had focal seizures at 16 months old. Magnetic resonance imaging (MRI) revealed right parietal leptomeningeal enhancement with white matter changes. MR angiography (MRA) showed cerebrovascular tortuosity and stenoses without evidence of vasculitis. She had extensive veno-lymphatic malformation in the thorax, abnormal renal vasculature, inferior vena cava (IVC) atresia, and bilateral pulmonary vein stenosis (PVS). Patient #2 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at four years old had an episode of status epilepticus. MRI revealed a right parietal infarct with surrounding leptomeningeal enhancement and MRA demonstrated abnormal caliber of the right middle cerebral artery (MCA), arterial tortuosity, and carotid aneurysms. His course was complicated by aortic root dilation and bilateral PVS. Patient #3 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at 16 months had a right sided focal motor seizure. MRI demonstrated infarct with associated sulcal enhancement predominantly in the left cerebral hemisphere. MRA found excessive vascular tortuosity and fenestrations. He has a dilated aortic root and ventricular septal defect (VSD).

CONCLUSION: We present three cases of APLAID complicated by significant cerebrovascular tortuosity and seizure and two with cerebral ischemia. The etiology of stroke and/or seizures in these patients is unclear, but vasculopathy leading to perfusion deficits, neuroinflammation, or thrombosis due to underlying thrombotic diathesis or abnormal vascular anatomy may have contributed. We recommend all patients with APLAID undergo monitoring for neurologic manifestations. Additionally, we highlight important vasculopathic findings such as PVS, where early recognition for directed treatment is critical.},
}

Humans
Female
*Phospholipase C gamma/genetics
Infant
Male
Magnetic Resonance Imaging
*Immunologic Deficiency Syndromes/genetics/complications
Magnetic Resonance Angiography

@article {pmid42895822,
year = {2026},
author = {Jiang, H and Zhao, T and Zhang, X and Moriyama, H},
title = {Abdominal ultrasound mitigates neurodegenerative pathology and alters specific gut microbial taxa in senescence-accelerated mice.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glag250},
pmid = {42895822},
issn = {1758-535X},
abstract = {Age-related changes in gut microbiota composition have been implicated in brain aging and cognitive decline, acting through the gut-brain axis on amyloid accumulation, tau pathology, synapse damage, and glial activation. Live microbial approaches such as probiotics, prebiotics, and fecal microbiota transplantation address this mechanism, but they still suffer from low efficacy and unknown safety issues. We tested whether abdominal ultrasound, an approach that does not involve microbes, can alleviate age-related neurodegeneration in the senescence-accelerated mouse strain SAMP8. We treated 6-month-old male SAMP8 mice for 1 month. We then assessed behavior, neuropathology, and synaptic proteins, and quantified four pre-specified fecal bacterial taxa. Ultrasound preserved neuronal survival in the hippocampal CA3, decreased amyloid-β load in the cortex and CA3, decreased tau hyperphosphorylation in all three regions, reduced Iba-1 and GFAP immunoreactive areas, and increased synaptophysin and cortical PSD-95. Neuronal survival in the cortex and CA1 did not differ significantly from sham-treated SAMP8 mice. In the gut microbiota, ultrasound significantly reduced the enriched taxon Tyzzerella, whereas the changes in Lactobacillus, Akkermansia and Atopobiaceae were large in magnitude but not statistically significant. In an exploratory analysis, four of 64 microbiota-neuropathology associations survived correction for multiple testing. Neither object recognition memory nor spatial memory differed significantly between treated and sham-treated SAMP8 mice. Abdominal ultrasound applied to the periphery therefore reduced age-associated neuropathology in the brain, accompanied by changes in specific gut microbial taxa whose causal contribution remains untested.},
}

@article {pmid42898166,
year = {2026},
author = {Zhu, J and Zeng, B and Zhu, W and Liu, Y and Li, X and Zhang, Y and Xu, Z and Xu, Q and Wu, W and Li, J and Shang, X and Lin, Y and Zhou, T and Lu, F and Qian, Y},
title = {Gut microbiota-driven imbalance of the gut-brain-immune homeostatic network in constipation: Pathogenic mechanisms and evolving therapeutic prospects.},
journal = {iScience},
volume = {29},
number = {11},
pages = {117850},
pmid = {42898166},
issn = {2589-0042},
abstract = {Chronic constipation (CC) is increasingly recognized as a systems-level disorder that cannot be explained by impaired intestinal motility alone. Here, we integrate evidence from clinical cohorts, animal models, and mechanistic studies to examine how gut microbial dysbiosis and altered microbial metabolites perturb epithelial barrier integrity, immune homeostasis, enteric neural activity, and gut-brain signaling. We propose a "gut-brain-immune homeostatic network" in which short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and other microbial signals may sustain self-reinforcing interactions linking dysmotility, inflammation, and neurobehavioral disturbances. We further evaluate microbiota-directed interventions, including prebiotics, probiotics, postbiotics, fecal microbiota transplantation, engineered bacteria, and multi-omics-guided personalized strategies. This framework reframes CC as a multisystem homeostatic disorder and provides a mechanistic basis for patient stratification, therapeutic target discovery, and precision interventions for constipation and related gut-brain-immune disorders.},
}

@article {pmid42898827,
year = {2026},
author = {Li, Y and Zhou, L and Huang, R and Wang, Y and Zhao, H and Sun, M and Zhang, Y and Wu, Z and Li, J},
title = {Gut microbiota in esophageal cancer: mechanisms, clinical implications, and therapeutic potential.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1955627},
pmid = {42898827},
issn = {1664-302X},
abstract = {Esophageal cancer (EC) is a highly prevalent and aggressive gastrointestinal malignancy. Late diagnosis and heterogeneous responses to chemoradiotherapy and immune checkpoint inhibitor (ICI) therapies severely challenge clinical management. Accumulating evidence suggests that gut microbiota dysbiosis influences esophageal mucosal malignant transformation, tumor progression, and therapeutic outcomes through the gut-esophageal axis. However, most existing research remains correlational. To bridge this gap, this review critically synthesizes the dysbiosis signatures of EC and establishes a five-tier evidence grading framework to rigorously distinguish causal mechanisms from preclinical inferences. This microbial regulation is predominantly driven by metabolite-mediated signaling, remodeling of the tumor immune microenvironment (TME), intestinal barrier disruption, and oncogenic pathway activation. We functionally classify EC-associated dysbiosis into pro-tumorigenic, anti-tumorigenic, and context-dependent taxa, emphasizing a multidimensional ecosystem perspective. Furthermore, we evaluate the utility of gut microbial signatures as predictive biomarkers for neoadjuvant therapy and prognosis. Microbiota-targeted intervention strategies, including fecal microbiota transplantation (FMT), microecological preparations, and Traditional Chinese Medicine (TCM), have entered clinical exploration as adjunctive approaches to optimize treatment efficacy. Finally, we address current translational barriers and propose future directions, emphasizing multi-omics integration, spatial transcriptomics, and artificial intelligence (AI). This provides an objective, mechanistically grounded framework for advancing microbiota-guided personalized oncology in EC.},
}

@article {pmid42898941,
year = {2026},
author = {Bai, X and Zhu, L and Sun, Y and Shi, Y and Zhou, P and Wang, C and Cui, L and Shi, L},
title = {Gut microbiota and innate immune barrier dysfunction in hepatic portal venous gas: a hypothesis-generating review.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1974872},
pmid = {42898941},
issn = {1664-3224},
mesh = {Humans ; *Immunity, Innate ; *Gastrointestinal Microbiome/immunology ; Intestinal Barrier Function ; *Portal Vein/immunology ; Animals ; Dysbiosis/immunology ; *Embolism, Air/immunology/microbiology ; },
abstract = {Hepatic portal venous gas (HPVG) is an uncommon radiographic sign whose prognosis is driven by bowel necrosis and shock rather than by intraportal gas. Immunological events along the gut-liver axis have not been synthesized for adult HPVG, and dedicated microbiome, metabolomic, gut-vascular barrier (GVB), and immune-profiling data are lacking. This hypothesis-generating review proposes gut dysbiosis as a putative contributor to mucosal and hepatic innate immune failure, inferred from cirrhosis, porto-sinusoidal vascular disease (PSVD), and intestinal ischemia/reperfusion. In those proxy states, loss of acetyl-CoA butyrate-production capacity, context-dependent bile-acid shifts, lipopolysaccharide-Toll-like receptor 4 priming, facultative-anaerobe expansion, and fermentative H2/CO2 pathways documented in cultured HPVG isolates-Clostridium perfringens (pyruvate-ferredoxin oxidoreductase-hydrogenase) and Escherichia coli (pyruvate-formate lyase-formate hydrogen lyase)-compromise epithelial and GVB integrity. These links are not assembled as a demonstrated sequence in adult HPVG. We propose a physical-core model in which a route of entry and a local driving pressure gradient are necessary, whereas pathway-defined fermentative isolates, dysbiosis, mucosal inflammation, ischemia, and impaired portal clearance are optional amplifiers. Iatrogenic or purely pressure-related HPVG can occur without dysbiosis or a substantial pathogen-associated molecular pattern load; in necrosis-driven HPVG, dysbiosis is proposed only as a concurrent immune amplifier; when HPVG occurs in cirrhosis or PSVD, portal hypertension is treated as a host modifier of barrier geometry and washout, not as an independent generator of intraportal gas. Portal vein thrombosis, portal hypertension, pneumatosis intestinalis, pyogenic liver abscess, and HPVG may share the portal vein as a conduit but are not interchangeable. No microbiota-directed intervention has been tested against an HPVG endpoint and none should delay source control; probiotics, rifaximin, fecal microbiota transplantation, diet, and phage remain research questions.},
}

Humans
*Immunity, Innate
*Gastrointestinal Microbiome/immunology
Intestinal Barrier Function
*Portal Vein/immunology
Animals
Dysbiosis/immunology
*Embolism, Air/immunology/microbiology

@article {pmid42899031,
year = {2026},
author = {O'Flaherty, EAA and van Sinderen, D},
title = {Faecal microbiota transplant revisited - potential metabolic outcomes of regional microbiome mismatches.},
journal = {Microbiome research reports},
volume = {5},
number = {3},
pages = {24},
pmid = {42899031},
issn = {2771-5965},
}

@article {pmid42899795,
year = {2026},
author = {Dai, Y and Song, P and Cheng, C and Cheng, L and Dai, C and Lu, W},
title = {Schaftoside, a functional flavonoid from fenugreek (Trigonella foenum-graecum L.), alleviates depression and cognitive deficits via the microbiome-gut-brain axis in stressed mice.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo04156f},
pmid = {42899795},
issn = {2042-650X},
abstract = {Depression involves dysregulation of central and peripheral networks, with gut microbiota alterations increasingly implicated in pathogenesis. Trigonella foenum-graecum L. (fenugreek), a functional food and medicinal herb, has been used traditionally for neurological disorders, yet its specific neuroprotective constituents remain poorly characterized. This study evaluated the antidepressant potential of schaftoside, the predominant flavonoid of fenugreek seed flavonoids, and explored its mechanisms involving the microbiome-gut-brain axis in a chronic restraint stress (CRS) mouse model. Male Kunming mice were subjected to CRS and orally administered schaftoside (20, 50, and 125 mg kg[-1]) or fluoxetine (10 mg kg[-1]) for 28 days. Behavioral assessments (tail suspension, forced swim, novel object recognition, and Y-maze) demonstrated that schaftoside dose-dependently ameliorated depressive-like behaviors and cognitive impairments. It attenuated hippocampal neuronal damage and neuroinflammation, restoring hippocampal 5-HT, NE, and ACh levels. Intestinal barrier integrity was improved, evidenced by enhanced tight junction proteins (ZO-1, occludin) and mucin (MUC2) expression, alongside reduced colonic pro-inflammatory cytokines and elevated IL-10. 16S rRNA profiling revealed that schaftoside reshaped gut microbiota composition, notably suppressing stress-enriched Bacteroides and promoting butyrate-producing Butyricicoccus. Untargeted metabolomics identified restoration of tryptophan and α-linolenic acid metabolism pathways. Spearman correlation analysis revealed significant associations between specific gut genera, fecal metabolites, and host inflammatory/neurochemical markers. Hippocampal transcriptomics indicated enrichment of cAMP signaling, dopaminergic, and serotonergic synapse pathways. Fecal microbiota transplantation (FMT) from schaftoside-treated donors partially recapitulated the behavioral, anti-inflammatory, and intestinal barrier-protective effects in antibiotic-pretreated recipient mice, accompanied by restoration of the gut microbiota and metabolite profiles. These findings demonstrate that schaftoside, the major flavonoid of fenugreek seeds, exhibits promising antidepressant-like potential through modulation of the microbiome-gut-brain axis, supporting the functional food application of fenugreek-derived flavonoids for stress-related mood disorders.},
}

@article {pmid42892458,
year = {2026},
author = {Ren, X and Yan, X and Tang, P and Jin, J and Qin, Z and Zhang, Y and Zhang, T and Yao, G and Yin, X and Zhao, Z and Wang, Z and Zhang, Q},
title = {Nifedipine-modulated gut microbiota attenuates hypertensive vascular injury through Bifidobacterium-associated inosine-Adora2b signaling.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {109684},
doi = {10.1016/j.phrs.2026.109684},
pmid = {42892458},
issn = {1096-1186},
abstract = {Although antihypertensive drugs mitigate hypertensive vascular injury, their vascular benefits are not fully explained by blood pressure reduction alone. Many cardiovascular drugs reshape the gut microbiota, which in turn influences their vascular pharmacology. We therefore investigated whether gut microbiota remodeling contributes to nifedipine-mediated vascular protection in high-salt hypertensive rats and a pilot patient cohort. Combining 16S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation, microbiota depletion, supplementation, and selective receptor antagonism, we found that nifedipine ameliorated gut dysbiosis. Transplantation of nifedipine-modulated microbiota improved intestinal barrier integrity and reduced vascular inflammation, oxidative stress, collagen deposition, and vascular smooth muscle cell (VSMC) phenotypic switching, while only marginally lowering blood pressure. Conversely, microbiota depletion markedly attenuated these vascular benefits despite preserving nifedipine-induced blood pressure lowering. These vascular benefits were associated with nifedipine-restored Bifidobacterium animalis subsp. lactis 420 (B420) and increased inosine availability. Supplementation with either recapitulated major vascular protective effects of nifedipine without statistically significant changes in blood pressure. In hypertensive patients, nifedipine treatment was associated with higher intestinal B420 abundance and inosine levels. In vitro, inosine modulated macrophages in an Adora2b- and Rap1-dependent manner, with accompanying changes in cAMP and KLF4, ameliorating VSMC dysfunction via paracrine signaling. In vivo, systemic Adora2b antagonism attenuated the vascular protective effects of both inosine and B420. Together, our findings support a gut microbiota-dependent component of nifedipine-mediated vascular protection that extends beyond blood pressure lowering, involving B420, increased inosine availability, and Adora2b signaling. We also nominate B420 and inosine as candidate adjuncts to calcium channel blocker therapy.},
}

@article {pmid42894314,
year = {2026},
author = {Zhao, M and Li, S and Fu, G and Deng, T and Jin, Y and Ye, Y and Li, Z},
title = {Evaluation of Clinical Practice Guidelines on Fecal Microbiota Transplantation in Adults: A Cross-Sectional Study.},
journal = {Journal of evidence-based medicine},
volume = {},
number = {},
pages = {e70202},
doi = {10.1111/jebm.70202},
pmid = {42894314},
issn = {1756-5391},
support = {2025‑AISJK‑02015//Ministry of Industry and Information Technology/ ; 2412055210//University-Industry Collaborative Education Program/ ; },
abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is an emerging multi-disease therapy, yet the quality and consistency of its available clinical practice guidelines (CPGs) remain unknown. This study aimed to systematically evaluate the quality, content coverage and recommendation consistency of FMT-related guidelines and develop an optimization framework for evidence-informed future guideline revision and standardized FMT clinical practice.

METHODS: We searched PubMed, Embase, Web of Science Core Collection, The Cochrane Library, CNKI, WanFang Data, and official websites of guideline development organizations and professional societies from inception to March 11, 2026. Two reviewers independently screened and selected CPGs with actionable recommendations and conducted quality evaluation via the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Intraclass correlation coefficient (ICC) with 95% confidence intervals (CIs) was computed for each AGREE II domain and interpreted according to Fleiss' criteria. Inter-guideline agreement was reported as the percentage of CPGs endorsing each recommendation.

RESULTS: Eighteen CPGs (3 general, 15 FMT-specific) with 191 recommendations were included. Applicability obtained the lowest AGREE II score (37.8%), followed by rigor of development (47.4%) and stakeholder involvement (49.7%). General guidelines scored higher than FMT-specific guidelines in applicability (62.5% vs. 32.9%) and stakeholder involvement (59.3% vs. 47.8%), but lower in rigor of development (38.9% vs. 49.1%). The coverage of recommendations showed marked inter‑guideline heterogeneity. Recurrent Clostridioides difficile infection (rCDI) was the most consistently recommended indication with the highest level of evidence (10/16). Over 75% of guidelines ignored transplant-center management, and non-CDI indications and key operational steps lacked sufficient high-certainty evidence. ICCs (0.86-0.97) showed excellent evaluator consistency.

CONCLUSIONS: Current FMT guidelines exhibit significant methodological deficiencies, heterogeneous recommendation coverage, and limited consensus beyond rCDI. FMT-specific guidelines show better developmental rigor but poorer applicability than general guidelines. Future FMT guideline development should establish core topic sets, adopt multidisciplinary collaborative mechanisms, and develop implementation toolkits with regular update protocols.},
}

@article {pmid42894858,
year = {2026},
author = {Geng, Z and Li, Q and Wang, D and Yang, H and Wang, H and Bao, J and Wang, Y and Wei, L},
title = {L-Histidine alleviates tacrolimus-induced islet dysfunction via the gut-pancreas axis.},
journal = {iScience},
volume = {29},
number = {11},
pages = {117802},
pmid = {42894858},
issn = {2589-0042},
abstract = {Tacrolimus is widely used after organ transplantation but can impair pancreatic β-cell function and glucose homeostasis. Using rodent models, antibiotic-mediated microbiota depletion, fecal microbiota transplantation, 16S rRNA sequencing, metabolomic profiling, and MIN-6 cells, we examined whether microbiota-associated L-histidine contributes to β-cell protection. Tacrolimus altered gut microbial composition and increased histidine-associated microbial and metabolic signals. L-histidine supplementation improved glucose tolerance and insulin secretion, reduced β-cell apoptosis, and increased PI3K/Akt/mTOR/p70S6K signaling and PDX-1, NeuroD1, and MafA expression. Microbiota depletion attenuated several protective effects of L-histidine, supporting a contribution of the gut microbiota to this response. These findings connect a microbiota-associated amino acid with tacrolimus-related β-cell dysfunction and provide a framework for investigating microbiota-metabolite contributions to metabolic complications of immunosuppression.},
}

@article {pmid42895099,
year = {2026},
author = {Liu, Y and Qiu, Y and Li, D and Zhai, S and Xia, T and Wang, M},
title = {Vinegar polyphenol extract alleviates alcohol-induced liver injury through suppressing the hepatic MAPK signaling pathway and restoring gut microbiota homeostasis and short-chain fatty acid generation in male mice.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo02941h},
pmid = {42895099},
issn = {2042-650X},
abstract = {Traditional brewed vinegar is rich in polyphenolic compounds that exhibit antioxidant, anti-inflammatory, and hepatoprotective activities. However, the protective mechanisms of vinegar polyphenol extract (VE) against alcohol-associated liver disease (ALD) involving gut homeostasis remain unclear. The phenolic composition of VE was characterized using UPLC-QTrap-MS/MS. Its hepatoprotective mechanisms in alcohol-treated mice were investigated through hepatic transcriptomic profiling and identification of key signaling pathways. Additionally, whether the hepatoprotective effects of VE were dependent on the gut microbiota were explored via antibiotic-mediated microbiota depletion and fecal microbiota transplantation. Twenty phenolic compounds were identified in VE, and 4-hydroxybenzoic acid was the predominant component accounting for 46.67%. VE administration at 750 mg kg[-1] significantly reduced serum ALT and AST levels, attenuated hepatic oxidative stress and inflammation, and suppressed alcohol-induced phosphorylation of p38, JNK, and ERK1/2. Meanwhile, VE restored the integrity of the intestinal barrier and reduced the LPS burden. Moreover, VE remodeled the gut microbiota by upregulating Akkermansia and Bacteroides and reducing Escherichia, which was accompanied by restoration of SCFA generation, notably acetic acid and propionic acid. Microbiota depletion weakened the protective effects of VE, whereas fecal microbiota transplantation restored its hepatoprotective activity. These findings suggest that VE alleviates alcohol-associated liver disease by suppressing the hepatic MAPK signaling pathway and restoring intestinal homeostasis. VE is a promising food-derived functional ingredient for the prevention of ALD.},
}

@article {pmid42895196,
year = {2026},
author = {Halder, U and Hamida, H and Kakar, K and Yang, X and Zhong, Y and Nagarkatti, M and Nagarkatti, P},
title = {Acute liver injury is triggered by dysbiosis and microbial translocation involving gut-liver axis.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2749977},
doi = {10.1080/19490976.2026.2749977},
pmid = {42895196},
issn = {1949-0984},
mesh = {Animals ; *Dysbiosis/microbiology/complications ; *Liver/microbiology/immunology/pathology ; *Bacterial Translocation ; Mice ; *Gastrointestinal Microbiome ; Intestinal Barrier Function ; Disease Models, Animal ; Humans ; Mice, Inbred C57BL ; Bacteria/classification/isolation & purification/genetics ; Male ; *Chemical and Drug Induced Liver Injury/microbiology ; },
abstract = {Acute liver injury (ALI) is a severe clinical condition that can progress to chronic liver failure, cirrhosis, or hepatocellular carcinoma, yet therapeutic options remain limited. Here, we investigated how hepatotoxin-induced gut-liver dysbiosis drives hepatic inflammation through microbial crosstalk. Using three murine ALI models, we assessed liver injury, intestinal barrier integrity, microbial composition along the gut-liver axis, and immune activation. Each hepatotoxin recapitulated distinct features of human ALI and induced unique patterns of hepatic and intestinal injury, enabling the progressive translocation of live bacteria from the gut to the liver and bloodstream. ALI was consistently associated with depletion of commensal taxa (Lactobacillaceae, Ruminococcaceae, and Bifidobacteriaceae) and enrichment of opportunistic pathogens (Enterococcaceae, Clostridiaceae, Enterobacteriaceae, and Burkholderiaceae). Dysbiosis also involved reduced gut bacteriophages and the expansion of viral families, including Retroviridae and Herpesviridae, in the liver and blood. Transplantation of the fecal or liver microbiota from ALI mice into microbiota-depleted recipients reproduced liver injury, immune activation, and intestinal barrier disruption, demonstrating that dysbiotic microbial communities alone are sufficient to trigger hepatic inflammation. These communities activated Th1/Th17 associated pathways (NF-κB, IL-17, TGF-β, and antigen presentation networks) and expanded pro-inflammatory immune populations. A key advance of this study is the direct comparison of fecal- versus liver-derived microbiota, revealing distinct mechanistic roles for each in driving liver pathology. Across all models, hepatotoxin-induced intestinal barrier breakdown drives gut-liver dysbiosis, microbial translocation, and immune-mediated liver injury. These findings uncover a unifying mechanism by which microbial imbalance reprograms hepatic immunity and accelerates ALI progression.},
}

Animals
*Dysbiosis/microbiology/complications
*Liver/microbiology/immunology/pathology
*Bacterial Translocation
Mice
*Gastrointestinal Microbiome
Intestinal Barrier Function
Disease Models, Animal
Humans
Mice, Inbred C57BL
Bacteria/classification/isolation & purification/genetics
Male
*Chemical and Drug Induced Liver Injury/microbiology

@article {pmid42891334,
year = {2026},
author = {Yu, Y and Wen, Q and Wang, X and Song, M and Yuan, T and Deng, F and Chai, J and Li, Y and Zhang, YP},
title = {Pioneering the canine model in microbiota-gut-brain research for social and affective disorders.},
journal = {iMetaOmics},
volume = {3},
number = {3},
pages = {e70113},
pmid = {42891334},
issn = {2996-9514},
abstract = {This commentary highlights the translational potential of canine models in investigating the microbiota-gut-brain (MGB) axis, focusing on their relevance to human social cognition and affective disorders, including major depressive disorder and autism spectrum disorder. While traditional rodent models provide foundational knowledge, the unique socio-behavioral complexity of dogs offers a potential bridge to study the shared neuroendocrine and microbial substrates underlying human psychopathology. This commentary outlines the promising avenues for canine-based research while critically addressing the practical limitations inherent in generalizing these findings to human populations, including genetic heterogeneity, standardization challenges, and ethical considerations. We propose a phased research pathway incorporating fecal microbiota transplantation and neurobehavioral phenotyping to define a clear trajectory for future translational research. Leveraging this canine platform creates a One Health paradigm, delivering mutual diagnostic and therapeutic advancements for both human and veterinary medicine, with applications for conditions such as anxiety and gastrointestinal disorders.},
}

@article {pmid42887877,
year = {2026},
author = {Carson, M and Meadows, V and Nejak-Bowen, K},
title = {Microbiome Targeted Therapies for Primary Sclerosing Cholangitis.},
journal = {Seminars in liver disease},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2983-7443},
pmid = {42887877},
issn = {1098-8971},
abstract = {Primary sclerosing cholangitis is a rare, progressive cholestatic liver disease of the intrahepatic and extrahepatic bile ducts with poor prognosis. The only life-extending treatment for PSC is liver transplantation, with up to 25% of post-transplant patients developing recurrent disease, highlighting an extrahepatic influence on disease. The gut-liver axis has been widely studied in the development and pathogenesis of PSC, with preclinical and clinical work demonstrating that targeting gut microbiota and its metabolites can elicit therapeutic effects against PSC. This review describes various microbiome-based therapeutics and their effectiveness in treating PSC, including antibiotics, probiotics, fecal microbiota transplantation, and bacteriophages. In conclusion, the use of microbiota-derived metabolites as potential therapeutics is also addressed.},
}

@article {pmid42888516,
year = {2026},
author = {Kelly, CR and Kelly, BJ and Wu, Q and Laine, L and Wu, GD and Kim, A and Fredell, L and Serra, S and Lewis, JD},
title = {Incidence and Risk Factors for C. difficile Reinfection After Faecal Microbiota Transplantation or Antibiotic Therapy.},
journal = {Alimentary pharmacology & therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1111/apt.71035},
pmid = {42888516},
issn = {1365-2036},
abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is an effective treatment for multiply recurrent C. difficile infection (mrCDI). Less is known about rates of reinfection after successful FMT. We aimed to estimate the incidence of CDI reinfection, 6 or more months after FMT, to determine whether rates differ between mrCDI treated with and without FMT and whether proton pump inhibitor (PPI) therapy increases the risk of reinfection.

METHODS: Among patients with mrCDI (defined as ≥ 2 recurrences after the initial CDI episode) we compared reinfection with CDI (defined as a first recurrence > 183 days after treatment completion) in patients who underwent antibiotics followed by FMT with those treated with antibiotics alone in Optum's de-identified Clinformatics Data Mart Database (OPTUM CDM). We also compared reinfection between those with and without PPI use in OPTUM CDM and the American Gastroenterological Association FMT Registry.

RESULTS: In OPTUM CDM, 6384 patients treated with antibiotics alone and 1786 with antibiotics + FMT met inclusion criteria (median follow-up 704 days). One-year and 3-year CDI reinfection incidences were 5% and 10% in the FMT group and 6% and 12% in the antibiotics group: Cox regression HR 0.89, 95% CI 0.73-1.08. PPI use was associated with an increased risk of reinfection following FMT (HR 1.57, 1.03-2.41) in OPTUM CDM and in the FMT Registry (HR 1.62, 95% CI 0.84-3.12).

CONCLUSIONS: CDI reinfection rates are low after successful FMT and similar to rates in patients treated with antibiotics alone. PPI use was associated with reinfection, supporting reassessment of the ongoing indication for PPI therapy in patients with mrCDI.},
}

@article {pmid42889310,
year = {2026},
author = {Wang, H and Ou, G and Xu, H and Liu, T and Jiang, Y and Wang, S and Wu, J and Wu, S and Deng, L and Xu, L},
title = {Gegen Qinlian decoction alleviates ulcerative colitis by remodeling the gut microbiota-bile acid axis and inhibiting NLRP3-mediated pyroptosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1895206},
doi = {10.3389/fimmu.2026.1895206},
pmid = {42889310},
issn = {1664-3224},
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Drugs, Chinese Herbal/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology ; Humans ; *Pyroptosis/drug effects ; *Bile Acids and Salts/metabolism ; Mice ; Caco-2 Cells ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Inflammasomes/metabolism ; },
abstract = {BACKGROUND: Gegen Qinlian Decoction (GQD) is used to treat intestinal disorders, but its mechanism in ulcerative colitis (UC) induced by combined high-fat diet (HFD) and dextran sulfate sodium (DSS) exposure remains unclear.

METHODS: A UC mouse model was induced by HFD plus DSS. GQD constituents were identified by UPLC-MS/MS. Colonic pathology and barrier integrity were assessed by H&E and immunofluorescence. Gut microbiota and bile acids were analyzed by 16S rRNA gene sequencing and targeted metabolomics. Transcriptomics, ELISA, Western blotting, fecal microbiota transplantation (FMT), and molecular docking were used to investigate mechanisms. LPS-stimulated Caco-2 cells were treated with 20 or 50 μM DCA; cell viability, NLRP3 inflammasome-related gene expression, and ZO-1/Occludin immunofluorescence were evaluated.

RESULTS: GQD ameliorated gut dysbiosis, decreasing the Firmicutes/Bacteroidetes ratio, increasing Akkermansia muciniphila, and reducing Clostridium perfringens. It remodeled bile acid metabolism, decreasing primary bile acids (CA, TCA, and CDCA, etc.) and increasing secondary bile acids (DCA, 6,7-DKLCA and 3β-DCA, etc.). Transcriptomics indicated inhibition of NOD-like receptor signaling. GQD suppressed NLRP3 inflammasome activation and reduced ASC, pro-caspase-1, cleaved caspase-1, GSDMD-N, and IL-18. Docking prioritized DCA as a candidate NLRP3-interacting metabolite. In Caco-2 cells, DCA dose-dependently reduced LPS-induced NLRP3, ASC, GSDMD, IL1B, and IL18 mRNA expression and partially restored ZO-1 and Occludin signals without appreciable cytotoxicity. FMT supported the involvement of gut microbiota in GQD-mediated anti-inflammatory effects.

CONCLUSION: GQD alleviates UC induced by combined HFD and DSS exposure by reshaping the gut microbiota and correcting bile acid dysregulation, thereby inhibiting NLRP3 inflammasome activation. This study highlights the gut microbiota-bile acid axis in GQD's therapeutic effects.},
}

Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Drugs, Chinese Herbal/pharmacology
*Gastrointestinal Microbiome/drug effects
*Colitis, Ulcerative/drug therapy/metabolism/microbiology
Humans
*Pyroptosis/drug effects
*Bile Acids and Salts/metabolism
Mice
Caco-2 Cells
Male
Disease Models, Animal
Mice, Inbred C57BL
Inflammasomes/metabolism

@article {pmid42890138,
year = {2026},
author = {Chen, Z and Gao, Z and Zhu, Z},
title = {Targeting the gut microbiota to promote motor rehabilitation after spinal cord injury: mechanisms, evidence, and translational challenges.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1946470},
doi = {10.3389/fneur.2026.1946470},
pmid = {42890138},
issn = {1664-2295},
mesh = {*Spinal Cord Injuries/rehabilitation/physiopathology/microbiology ; Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; Translational Research, Biomedical ; Recovery of Function/physiology ; Fecal Microbiota Transplantation ; *Dysbiosis ; },
abstract = {Spinal cord injury (SCI) is a devastating central nervous system trauma that frequently results in permanent motor dysfunction. Over the past decade the gut microbiota has emerged as a potentially modifiable contributor to secondary injury and neural repair, giving rise to the concept of the gut-spinal cord axis. In this narrative review we synthesize current understanding of how SCI-associated gut dysbiosis may relate to the recovery of motor function, focusing on immune modulation, microbial metabolites such as short-chain fatty acids and bile acids, and gut-central nervous system signaling. Throughout, we deliberately separate evidence obtained in SCI models or in people with SCI from mechanistic evidence generated in other diseases or experimental systems, because conflating these sources is a recurring source of over-interpretation in this field. We then summarize microbiota-targeted interventions studied in animal models-probiotics and prebiotics, fecal microbiota transplantation (FMT), antibiotics and bacteriophages, and direct supplementation with microbial metabolites-and appraise the small, predominantly observational human literature. Several of these interventions improve locomotor outcomes in rodent SCI models, but, with rare exceptions, the causal chain from a microbial change to a functional improvement has not been demonstrated within a single SCI study, and no randomized controlled trial in people with SCI has used motor function as its primary endpoint. We conclude by dissecting the principal translational barriers-inter-individual variability in microbiota composition, uncertain intervention timing and duration, unresolved safety questions, and the absence of standardized pre-clinical-to-clinical pipelines-and by outlining the study designs and reporting standards required to move this field from association toward causation.},
}

*Spinal Cord Injuries/rehabilitation/physiopathology/microbiology
Humans
Animals
*Gastrointestinal Microbiome/physiology
Translational Research, Biomedical
Recovery of Function/physiology
Fecal Microbiota Transplantation
*Dysbiosis

@article {pmid42890816,
year = {2026},
author = {Peng, O and Liu, Y and Wang, X and Huang, Y and Yang, Y and Kang, Q and Geng, R and Hu, G and Lv, A and Hu, F and Xia, Y and Luo, X and Liao, J and He, Y and Kuang, Z and Du, Y and Zhang, Y and Xue, C and Han, Z and Li, WJ and Dong, L and Zhang, H and Cao, Y},
title = {Akkermansia muciniphila enhances chicken resistance to infectious bronchitis virus by boosting GABA synthesis and suppressing the NF-κB inflammatory pathway.},
journal = {iMetaOmics},
volume = {3},
number = {1},
pages = {e70086},
doi = {10.1002/imo2.70086},
pmid = {42890816},
issn = {2996-9514},
abstract = {Infectious bronchitis virus (IBV) is a major viral pathogen causing substantial economic losses in the global poultry industry. However, the limited efficacy of commercial vaccines and the absence of approved antiviral drugs underscore the urgent need for novel strategies to combat IBV, particularly in the context of antibiotic-free poultry production. Emerging evidence suggests that gut microbiota plays a crucial role in shaping host immunity and antiviral resilience. In this study, we demonstrated that gut microbiota composition is a key determinant of IBV resistance in chickens, as revealed through a fecal microbiota transplantation (FMT) model. Utilizing multi-omics approaches, we conducted a comprehensive characterization of microbiomic, viromic, and metabolic differences among adult chickens, young chickens, and FMT-treated young chickens for the first time, establishing a mechanistic link between gut microbiota and IBV resistance. Building on these insights, longitudinal microbiome profiling in a newly developed persistent IBV infection model identified Akkermansia muciniphila as the key bacterium conferring IBV resistance, with its administration improving survival rates from 30-35% to 90-95%. Additionally, two novel candidate probiotics, Cloacibacillus porcorum and Neglecta timonensis, exhibited moderate yet measurable protective effects. Mechanistic investigations revealed that Akkermansia muciniphila enhances γ-aminobutyric acid (GABA) production, which suppresses NF-κB-driven inflammatory responses, reduces pro-inflammatory cytokine levels, alleviates nephritis, and upregulates antiviral interferon expression, thereby fortifying host defenses against IBV infection. These findings provide a scientific foundation for deploying live biotherapeutic products as an intervention strategy against IBV and highlight the broader potential of gut microbiota modulation in mitigating infectious diseases and optimizing poultry health management.},
}

@article {pmid42891232,
year = {2026},
author = {Xu, T and Tao, X and Fang, D and Zhang, H and Wang, Z and Liu, Y},
title = {Lactobacillus derived small RNAs protect against Klebsiella pneumoniae infection.},
journal = {iMeta},
volume = {},
number = {},
pages = {e70184},
doi = {10.1002/imt2.70184},
pmid = {42891232},
issn = {2770-596X},
abstract = {Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major multidrug-resistant pathogen with limited treatment options. Plant-derived natural products have broad biological activities, but their protective effects against extraintestinal multidrug-resistant bacterial infections remain poorly understood. Herein, we show that selected plant-derived natural products protect mice against CRKP pulmonary infection by remodeling the gut microbiota. Fecal microbiota transplantation and microbiota-depletion experiments demonstrated that this protection was microbiota dependent, with Lactobacillus emerging as a key genus associated with reduced pulmonary bacterial burden. Among four isolated Lactobacillus species, Lactobacillus murinus (L. murinus) conferred the strongest protection against CRKP infection. Mechanistically, L. murinus-derived membrane vesicles (MVs) delivered the small RNA mim-miR-21a-5p to pulmonary macrophages, where it targeted PDCD4 and activated the Nrf2/SOD2 antioxidant pathway. This signaling cascade preserved mitochondrial oxidative phosphorylation, promoted an M2-like macrophage phenotype, and ultimately restricted CRKP infection. Consistent with these findings, intestinal Lactobacillus, particularly L. murinus, was reduced in patients with CRKP infection compared with healthy controls. Collectively, our findings reveal a mechanism by which plant-derived natural products enhance host resistance to CRKP through microbiota remodeling and identify L. murinus-derived small RNAs and membrane vesicles as key mediator of this gut-lung protective axis.},
}

@article {pmid42880811,
year = {2026},
author = {Juanola, A and Moreta, MJ and Solé, C and Sánchez, J and Albillos, A and Martínez González, J and Poca Sans, M and Alvarado, E and Campos-Varela, I and Cespedes, C and Alonso, S and Bañares, R and Fortea, JI and Puente, Á and Llop, E and Fernández-Carrillo, C and Moya, A and Ruiz-Ruiz, S and Fernandez-Real, JM and Mayneris-Perxachs, J and Bonfill, E and Rivera, C and Pich, J and Piano, S and Solà, E and Torres, F and Iavarone, S and Pérez-Guasch, M and Casanova, NC and González-Suárez, B and Fabrellas, N and Graupera, I and Pose, E and Ginès, P},
title = {Randomised, double-blind, placebo-controlled trial of faecal microbiota transplantation in patients with decompensated cirrhosis: the Livergut protocol.},
journal = {BMJ open},
volume = {16},
number = {10},
pages = {e118486},
doi = {10.1136/bmjopen-2026-118486},
pmid = {42880811},
issn = {2044-6055},
}

@article {pmid42881491,
year = {2026},
author = {Zehra, H and Kuchma, N and Lin, AW and Morris, G and Solano, O and Lopez, S and Kabage, AJ and Vaughn, BP and Weingarden, A and Fischer, M and Khoruts, A and Teigen, L},
title = {The Trajectory of Gastrointestinal Symptom Experience Following Fecal Microbiota Transplant for Recurrent Clostridioides Difficile Infection.},
journal = {Journal of clinical gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCG.0000000000002424},
pmid = {42881491},
issn = {1539-2031},
abstract = {INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) increases the risk of persistent gastrointestinal symptoms after treatment. Although fecal microbiota transplantation (FMT) effectively prevents CDI recurrence after antibiotics, the trajectory of gastrointestinal symptom severity remains poorly characterized.

METHODS: We tracked gastrointestinal symptom severity in a prospective, multicenter cohort study of adults with rCDI after treatment with standardized FMT products. Patients who experienced a CDI recurrence during the follow-up period were excluded. The IBS Symptom Severity Scale (IBS-SSS) was used as a measure of symptom severity, not as a diagnostic tool. Patients completed the IBS-SSS at the time of FMT, 1-week, 1-month, and 3-months post-FMT. The primary outcome was the change in IBS-SSS score after treatment. Subgroup analyses were conducted among patients with baseline IBS-SSS ≥175 (moderate/severe symptom severity) and <175 (none/mild symptom severity). Linear mixed-effects models were used to evaluate longitudinal changes and identify clinical predictors of IBS-SSS scores.

RESULTS: Among 107 patients included, median IBS-SSS scores decreased from 170 (range: 0 to 440) at baseline to 76 (range: 0 to 390) at week 1 and 54 (0 to 445) at month 3 (P<0.001). In those with baseline IBS-SSS ≥175 (n=51), 64% had none or mild symptom severity at month 3. In those with baseline IBS-SSS <175 (n=53), symptom severity was observed to remain as none or mild at month 3 in all but one patient.

CONCLUSION: FMT administered for prevention of rCDI was followed by a rapid (1 wk) and sustained (3 mo) reduction in gastrointestinal symptom scores in patients who did not develop CDI recurrence. These data help characterize the expected early post-FMT symptom trajectory, providing foundational evidence to better inform patient expectations and future interventions for persistent symptoms.},
}

@article {pmid42881530,
year = {2026},
author = {Springer, R and Claus, P and Hörner, M and Otto, C and Burkard, N and Lauerer, J and Deinlein, H and Fekete, A and Schmitz, W and Seyfried, F and Schlegel, N},
title = {High-fat diet-derived metabolite uridine diphosphate (UDP) impairs epithelial regeneration by P2Y 6 -receptor signaling.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2748160},
doi = {10.1080/19490976.2026.2748160},
pmid = {42881530},
issn = {1949-0984},
mesh = {Animals ; Male ; *Diet, High-Fat/adverse effects ; Rats, Wistar ; *Obesity/metabolism/microbiology ; Rats ; Signal Transduction ; *Uridine Diphosphate/metabolism ; Gastrointestinal Microbiome ; *Intestinal Mucosa/metabolism ; *Receptors, Purinergic P2/metabolism/genetics ; *Regeneration ; Intestinal Barrier Function ; Feces/microbiology ; },
abstract = {Obesity is associated with a chronic low-grade inflammation affecting metabolic changes and organ dysfunction. Impairment of the intestinal epithelial barrier (IEB) and alterations in gut microbiota are considered to contribute to this phenotype by largely undefined mechanisms. Here, we used a diet-induced obesity model in rats to investigate the early interplay between a high-fat diet (HFD), gut microbiota composition, metabolic stool contents and IEB regeneration. Male Wistar rats received either a high-fat diet or a low-fat diet (LFD) ad libitum. HFD feeding resulted in weight gain and impaired oral glucose tolerance. Impairment of IEB function was evident by augmented lipopolysaccharide levels in the blood and reduced expression of junctional proteins Claudin-3, 4, and Desmoglein-2 in colonic samples of HFD rats. 16S-rRNA marker-gene sequencing of colonic microbiota revealed decreased phylogenetic diversity in HFD rats and significant alterations in microbial community composition. Detailed analysis revealed that content from HFD rats impaired intestinal epithelial regeneration in organoid assays. Metabolomic profiling identified uridine monophosphate/uridine diphosphate (UMP/UDP) metabolites as strongly enriched in HFD samples. UDP emerged as a key metabolite mediating impaired epithelial regeneration through P2Y6 receptor signaling, as pharmacological inhibition of P2Y6 with antagonist MRS2578 attenuated both UDP- and HFD-induced loss of epithelial regeneration. In summary, these data demonstrate that the diet-dependent stool metabolite UDP compromises intestinal epithelial repair via P2Y6 receptor signaling in early obesity. These findings link impaired epithelial regeneration to the onset of obesity-associated low-grade inflammation.},
}

Animals
Male
*Diet, High-Fat/adverse effects
Rats, Wistar
*Obesity/metabolism/microbiology
Rats
Signal Transduction
*Uridine Diphosphate/metabolism
Gastrointestinal Microbiome
*Intestinal Mucosa/metabolism
*Receptors, Purinergic P2/metabolism/genetics
*Regeneration
Intestinal Barrier Function
Feces/microbiology

@article {pmid42882498,
year = {2026},
author = {Siemińska, I},
title = {The Gut Microbiota-Immunity Axis in Colorectal Cancer: Implications for Immunotherapy and Clinical Translation.},
journal = {Cells},
volume = {15},
number = {19},
pages = {},
doi = {10.3390/cells15191800},
pmid = {42882498},
issn = {2073-4409},
mesh = {Humans ; *Colorectal Neoplasms/immunology/therapy/microbiology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; *Translational Research, Biomedical ; Animals ; *Immunity ; },
abstract = {Colorectal cancer (CRC) arises within a complex microbial ecosystem that may influence carcinogenesis, tumor immunity, and therapeutic response. This is particularly relevant in metastatic disease, where most tumors are microsatellite-stable/mismatch repair-proficient (MSS/pMMR) and derive little meaningful benefit from immune checkpoint inhibitor (ICI) monotherapy. Specific pathobionts, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, have been implicated in genotoxic, inflammatory, and checkpoint-related mechanisms that may contribute to tumor progression and immune evasion, whereas selected commensals and microbiota-derived metabolites may support antitumor immunity in a context-dependent manner. This review integrates translational evidence linking microbial taxa and functions, metabolites, neutrophil biology, bacterial extracellular vesicles, and T-cell dysfunction with CRC progression and immunotherapy response. This review critically examines emerging microbiome-directed strategies, including fecal microbiota transplantation, next-generation probiotics, defined bacterial consortia, dietary and perioperative interventions, postbiotics, and bacteriophage-based approaches, as potential means of modifying immune resistance in MSS/pMMR CRC. Although early clinical signals from microbiota-modulating combinations are encouraging, the available evidence remains limited by small cohorts, heterogeneous interventions, and the absence of randomized CRC-specific studies. Microbiome-based biomarkers and therapeutics therefore remain investigational, and standardized sampling, prospective validation, and carefully designed trials will be required before microbiome modulation enters routine CRC care.},
}

Humans
*Colorectal Neoplasms/immunology/therapy/microbiology
*Immunotherapy/methods
*Gastrointestinal Microbiome/immunology
*Translational Research, Biomedical
Animals
*Immunity

@article {pmid42883057,
year = {2026},
author = {Zhang, J and Sun, Y and Li, X and You, D and Zhang, Z and Xu, M and Wu, D},
title = {Effects of Colostrum-Period Fecal Microbiota Transplantation on Growth Performance, Immune Function and Gut Microbiota in Pre-Weaned Calves.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {19},
pages = {},
doi = {10.3390/ani16193088},
pmid = {42883057},
issn = {2076-2615},
support = {2023LHMS03048//the Natural Science Foundation of Inner Mongolia Autonomous Region/ ; },
abstract = {Neonatal calf diarrhea caused by intestinal microbial dysbiosis severely restricts rearing efficiency, and fecal microbiota transplantation (FMT) emerges as a promising antibiotic-free strategy for regulating gut homeostasis. Nevertheless, to the best of our knowledge, the effects of colostrum-period FMT and the functional differences between colonic and colostrum delivery routes remain poorly characterized in pre-weaned dairy calves. We hypothesized that colostrum-period FMT would accelerate gut microbiota maturation, improve immune status and reduce diarrhea incidence in pre-weaned calves, with delivery-route-dependent effects. This study aimed to investigate how two colostrum-phase FMT delivery routes shape growth performance, serum immune profiles and gut microbiota in neonatal Holstein calves. Sixty newborn calves were randomly assigned to three groups (n = 20 per group): control (no FMT), colon-FMT (colonic perfusion), and colostrum-FMT (FMT mixed with colostrum). Donor feces were homogenized with sterile saline at a 1:9 ratio for FMT suspension preparation, and the trial lasted 56 days. For growth performance, the colon-FMT calves exhibited significantly higher average daily gain from D29 to D56 (p < 0.05). In terms of intestinal health, the colostrum-FMT group exhibited lower diarrhea incidence during D15-28 (p < 0.05) but markedly higher diarrhea rates during D29-56 (p < 0.01). For serum immunity, colon-FMT calves had elevated serum IgG at D14 (p < 0.05). At D56, the concentrations of IL-2 (p < 0.01) and IL-4 (p = 0.05) were significantly lower in the colostrum-FMT group than the colon-FMT group; no intergroup differences were detected for other serum cytokines and immunoglobulins. 16S rRNA gene sequencing of D28 fecal samples revealed that the colon-FMT group possessed a significantly higher relative abundance of Lactobacillus compared with the other two treatments (p < 0.05). Collectively, colonic FMT is associated with remodeling intestinal microbiota by enriching beneficial Lactobacillus, improved late-stage growth and sustained long-term intestinal health in pre-weaned calves, whereas colostrum-mediated FMT only provides transient protection against early diarrhea.},
}

@article {pmid42884619,
year = {2026},
author = {Ibrahim, I and Lawrence, K and Forte, OA and Huitt, L and Naidu, NC and Ajibola, N and Xu, J and Boakai, RK and Akabanda, F and Owusu-Kwarteng, J and Ajayi, OS and Ayariga, JA},
title = {Diffuse Idiopathic Skeletal Hyperostosis (DISH): Potential Links Between Gut Microbiota and Spinal Degenerative Diseases.},
journal = {Nutrients},
volume = {18},
number = {19},
pages = {},
doi = {10.3390/nu18193168},
pmid = {42884619},
issn = {2072-6643},
support = {Title III- HBGI-RES//United States Department of Education/ ; },
mesh = {Humans ; *Hyperostosis, Diffuse Idiopathic Skeletal/microbiology ; *Gastrointestinal Microbiome/physiology ; *Intervertebral Disc Degeneration/microbiology ; Dysbiosis ; Animals ; },
abstract = {Diffuse Idiopathic Skeletal Hyperostosis (DISH) is a systemic, non-inflammatory skeletal disorder characterized by progressive calcification and ossification of spinal ligaments and entheses. Its strong associations with aging, obesity, type 2 diabetes, and metabolic syndrome raise the possibility that metabolic and inflammatory pathways may contribute to disease development. The gut microbiota participates in nutrient metabolism, short-chain fatty acid production, bile-acid transformation, intestinal-barrier maintenance, and immune regulation; these functions provide a plausible framework for examining whether intestinal dysbiosis may influence spinal and musculoskeletal tissues. This narrative review therefore evaluates the potential relationship between gut microbiota, DISH, and related spinal degenerative diseases. It considers the nutritional, metabolic, immunological, and host-interaction functions of the gut microbiota before examining proposed gut-spine, gut-bone, gut-joint, gut-disc, gut-ligament, and gut-muscle pathways. Particular attention is given to the apparent paradox that most microbiome-bone evidence concerns osteoporosis and bone loss, whereas DISH is characterized by excessive ectopic bone formation. Differences in short-chain fatty acid concentration, receptor expression, local versus systemic signaling, and osteoblast-osteoclast microenvironments may produce divergent skeletal effects, but these mechanisms have not been tested directly in DISH. Recent studies support associations between selected microbial taxa and intervertebral disc degeneration or spinal stenosis; however, direct clinical evidence linking gut microbiota to DISH remains limited. Consequently, dietary modification, probiotics, prebiotics, and fecal microbiota transplantation should be regarded as research considerations rather than established treatments for DISH. Well-characterized case-control and longitudinal studies integrating microbiome profiling, metabolomics, inflammatory markers, and serial imaging are required to determine whether reproducible microbial or metabolite signatures precede DISH onset or progression. The pathways discussed in this review are therefore presented as biologically plausible, testable hypotheses and not as established causal relationships.},
}

Humans
*Hyperostosis, Diffuse Idiopathic Skeletal/microbiology
*Gastrointestinal Microbiome/physiology
*Intervertebral Disc Degeneration/microbiology
Dysbiosis
Animals

@article {pmid42884675,
year = {2026},
author = {Yang, F and Xie, S and Yang, W and Zhu, C and Chen, Y and Yang, H and Yuan, H and Li, Q},
title = {Multi-Omics Analysis Reveals the Potential Role of Inonotus obliquus in Mit-Igating Hemolytic Jaundice.},
journal = {Nutrients},
volume = {18},
number = {19},
pages = {},
doi = {10.3390/nu18193225},
pmid = {42884675},
issn = {2072-6643},
support = {No. CKD/SXMU-2025-07//Shanxi Medical University/ ; No. 202303021221129//Shanxi Science and Technology Department/ ; },
mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; Phenylhydrazines ; Male ; Liver/metabolism/drug effects ; Multiomics ; Bilirubin/blood ; Disease Models, Animal ; Limosilactobacillus reuteri ; *Jaundice/drug therapy/chemically induced ; *Plant Extracts/pharmacology ; },
abstract = {Background: Hemolytic jaundice, characterized by excessive bilirubin production and hepatic dysfunction, currently lacks effective therapeutic strategies targeting its underlying mechanisms. Methods: This study evaluated the therapeutic potential of the aqueous extract of Inonotus obliquus (IO) in ameliorating hemolytic jaundice through modulation of the gut-liver axis. A murine model of hemolytic jaundice was induced by phenylhydrazine (PHZ) administration, and IO was orally administered as the intervention. Antibiotic depletion and FMT verified gut microbiota dependence. Liver injury, serum bilirubin, gut microbiome, and metabolites were assessed. Results: IO treatment significantly alleviated PHZ-induced hemolytic jaundice in mice. Notably, antibiotic-mediated depletion of the gut microbiota abolished the hepatoprotective effects of IO, whereas fecal microbiota transplantation (FMT) from IO-treated donors conferred marked amelioration of hyperbilirubinemia in recipient mice. Integrative multi-omics analysis identified Limosilactobacillus reuteri and Lactobacillus johnsonii as the predominant microbial species altered by IO. Furthermore, IO upregulated the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) in both hepatic and intestinal tissues and also increased the expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2). These alterations were correlated with an increased excretion of bile acids and bilirubin into the intestinal lumen, thereby mitigating hepatic injury. This process may be associated with the modulation of gut microbiota. Conclusions: These findings collectively provide evidence of a significant correlation between IO treatment and the mitigation of hemolytic jaundice, achieved by modulating the enterohepatic circulation of bile acids and bilirubin through the regulation of gut microbiota. Our results highlight the potential of IO as a microbiota-directed nutritional strategy for the management of jaundice.},
}

Animals
Mice
*Gastrointestinal Microbiome/drug effects
Phenylhydrazines
Male
Liver/metabolism/drug effects
Multiomics
Bilirubin/blood
Disease Models, Animal
Limosilactobacillus reuteri
*Jaundice/drug therapy/chemically induced
*Plant Extracts/pharmacology

@article {pmid42884732,
year = {2026},
author = {Samardžić, S and Božić, DD and Drobac, M and Marčetić, M and Arsenijević, J and Medarević, D and Maksimović, Z},
title = {The Gut Microbiota as a Mediator of the Metabolic Benefits of Fungi and Their Polysaccharides: A Review of Evidence Addressing Causality.},
journal = {Nutrients},
volume = {18},
number = {19},
pages = {},
doi = {10.3390/nu18193281},
pmid = {42884732},
issn = {2072-6643},
support = {451-03-33/2026-03/200161; 451-03-34/2026-03/200161//Ministry of Science, Technological Development, and Innovation/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Prebiotics/administration & dosage ; *Fungi/metabolism ; *Polysaccharides ; *Fungal Polysaccharides ; *Metabolic Diseases/microbiology ; },
abstract = {Prebiotic supplementation has emerged as a promising strategy to ameliorate metabolic disorders through beneficial reshaping of the gut microbiota. Accumulating evidence suggests that fungi and their polysaccharides (e.g., those from Auricularia auricula-judae, Boletus edulis, Hirsutella sinensis, Isaria cicadae, Ramaria botrytoides, and Wolfiporia cocos) possess considerable potential in this context. The present review summarizes studies providing data relevant to the potential involvement of the gut microbiota in mediating the metabolic benefits of fungal interventions. Observed outcomes, potentially linked to the gut microbiota, included reductions in body, visceral fat, and liver weights, improved lipid and glycemic profiles, enhanced insulin sensitivity, and decreased circulating lipopolysaccharide, leptin, and proinflammatory cytokines (TNF-α, IL-1β, IL-6). Upregulation of tight junction proteins in the colon implied strengthened gut barrier function. Histological analyses revealed smaller adipocytes and attenuation of hepatic steatosis. Additional effects included stimulation of white adipose tissue browning and enhanced hepatic thermogenesis. Alterations in gut microbiota composition were diverse; however, a reduction in the Firmicutes/Bacteroidetes ratio was commonly reported. Furthermore, oral administration of bacterial species enriched by fungal interventions, such as Papillibacter cinnamivorans, Parabacteroides goldsteinii, Bacteroides intestinalis, Lactobacillus johnsonii, and Enterococcus casseliflavus, reproduced the metabolic improvements, supporting their possible mediating role. Collectively, current evidence indicates that fungi and their polysaccharides may exert metabolic benefits, at least in part, through gut microbiota modulation; however, further investigation is needed to determine the extent to which the gut microbiota contributes causally to these benefits.},
}

Humans
*Gastrointestinal Microbiome/physiology
Animals
*Prebiotics/administration & dosage
*Fungi/metabolism
*Polysaccharides
*Fungal Polysaccharides
*Metabolic Diseases/microbiology

@article {pmid42885915,
year = {2026},
author = {Gries, M and Schäfer, KH and Endres, K},
title = {Targeting the microbiota-gut-brain axis in Alzheimer's and Parkinson´s disease: recent therapeutic approaches.},
journal = {Expert opinion on therapeutic targets},
volume = {},
number = {},
pages = {},
doi = {10.1080/14728222.2026.2748747},
pmid = {42885915},
issn = {1744-7631},
abstract = {INTRODUCTION: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders with limited disease-modifying treatment options. Evidence suggests that the microbiota-gut-brain axis (MGBA) plays a role in these diseases by facilitating communication between the gut and the central nervous system. Associations have been found between altered gut microbiota composition and function, impaired barrier integrity, dysregulated metabolite production, and immune activation to neuroinflammation and progressive neurodegeneration.

AREAS COVERED: This review summarizes and critically assesses recent studies from the past year to provide an updated overview of therapeutic strategies targeting the MGBA in both diseases. We discuss dietary interventions, probiotics, postbiotics, microbial metabolites, and approaches targeting gut barrier function. We also highlight strategies such as fecal transplantation, photobiomodulation, and PD-targeted metabolism therapies using butyrate and resistant starch.

EXPERT OPINION: While these interventions have shown promising results in preclinical and early clinical trials, their clinical application is limited by methodological heterogeneity, interindividual variability and a lack of standardized protocols. Successful implementation requires carefully designed clinical trials, particularly longitudinal studies of presymptomatic cohorts, standardized microbiome analyses, and integrated multi-omics approaches to elucidate causal relations and facilitate personalized treatment strategies.},
}

@article {pmid42886170,
year = {2026},
author = {Park, K and Joo, MK and Lee, IH and Woo, JH and Park, HS and Kong, CH and Jung, SY and Woo, SY and Kim, JY and Park, HJ and Kim, JW and Kim, DH and Ryu, JH and Choi, JH},
title = {Schizophrenia-associated gut microbiota are linked to reduced colonic PRODH expression and behavioral changes in mice.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2748081},
doi = {10.1080/19490976.2026.2748081},
pmid = {42886170},
issn = {1949-0984},
mesh = {Animals ; Male ; *Proline Oxidase/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; *Schizophrenia/microbiology/physiopathology ; *Gastrointestinal Microbiome ; *Colon/microbiology/enzymology ; Humans ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/isolation & purification/enzymology ; Behavior, Animal ; Proline/blood ; },
abstract = {Schizophrenia (SCZ) is a chronic neuropsychiatric disorder whose biological basis remains incompletely understood. Growing evidence implicates the gut-brain axis in SCZ, but the host pathways through which disease-associated microbiota may influence behavior remain unclear. Here, we examined whether the gut microbiota from patients with SCZ is associated with behavioral and metabolic alterations in male C57BL/6N mice. Fecal microbiota transplantation (FMT) from patients with SCZ was associated with impaired short-term recognition memory, reduced social novelty preference, and decreased prepulse inhibition in recipient mice. Transcriptomic profiling of colonic tissue identified reduced expression of Prodh, which encodes proline dehydrogenase (PRODH), together with elevated plasma proline levels. Comparative microbiome analyses identified a five-species candidate consortium associated with the SCZ donor microbiome - Escherichia fergusonii, Shigella sonnei, Morganella morganii, Citrobacter freundii, and Enterococcus faecalis. Oral administration of this five-species mixture (5-SM) was associated with similar behavioral changes, reduced colonic PRODH expression, and hyperprolinemia in mice. Together, these findings support a possible association between schizophrenia-associated changes in the gut microbiota, altered intestinal proline metabolism, and behavioral changes in mice.},
}

Animals
Male
*Proline Oxidase/genetics/metabolism
Mice
Mice, Inbred C57BL
*Schizophrenia/microbiology/physiopathology
*Gastrointestinal Microbiome
*Colon/microbiology/enzymology
Humans
Fecal Microbiota Transplantation
Bacteria/classification/genetics/isolation & purification/enzymology
Behavior, Animal
Proline/blood

@article {pmid42886304,
year = {2026},
author = {Zhu, Y and Ma, J and Wang, D and Cui, M and Peng, J and Lu, X and Pei, X and Wang, Y and Lv, J and Yan, Y and Ma, W and Zhao, M and You, S and Ma, J and Tang, Y and Zhu, Y},
title = {Curcumin alleviates metabolic dysfunction-associated steatotic liver disease via gut microbiota-dependent epigenetic alterations.},
journal = {Molecular biomedicine},
volume = {7},
number = {1},
pages = {},
pmid = {42886304},
issn = {2662-8651},
support = {82300661//National Natural Science Foundation of China/ ; 82203866//National Natural Science Foundation of China/ ; 2024AH030020//Outstanding Youth Science Foundation of the Department of Education of Anhui Province/ ; 2308085QH246//Natural Science Foundation of Anhui province/ ; KJ2021A0205//Natural Science Foundation of the Anhui Higher Education Institutions/ ; 2022xkjT013//Basic and Clinical cooperative research program of Anhui Medical University/ ; 2023xkj002//Scientific Research Foundation of Anhui Medical University/ ; },
mesh = {Animals ; *Epigenesis, Genetic/drug effects ; *Curcumin/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Fatty Liver/drug therapy/metabolism/genetics ; Rats ; Male ; Liver/metabolism/drug effects/pathology ; Diet, High-Fat/adverse effects ; Humans ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; },
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent, yet effective therapies remain limited. Curcumin (Cur), a polyphenol with well-documented metabolic benefits, shows therapeutic promise in MASLD, but its efficacy and underlying mechanisms remain incompletely understood. A meta-analysis of seven clinical studies indicated that Cur supplementation reduced serum aminotransferase levels, supporting its potential clinical benefit. In high-fat diet (HFD)-fed rats, Cur reduced hepatic lipid accumulation and metabolic dysfunction, whereas these effects were markedly weakened in antibiotic-induced pseudo-germ-free rats, indicating microbiota dependence. Fecal microbiota transplantation from Cur-treated donors transferred these metabolic and histological benefits to antibiotic-conditioned recipients. Fecal 16S rRNA sequencing identified Clostridium_sensu_stricto_1 (C. sensu) as a Cur-suppressed, pro-steatotic taxon, and targeted reconstitution of this taxon abolished Cur-mediated protection. Untargeted hepatic metabolomics and liquid chromatography-mass spectrometry identified kynurenine (KYN) as a C. sensu-derived metabolite and showed that Cur reduced hepatic KYN accumulation. Integrated H3K27ac ChIP-seq, bulk RNA-seq, and single-cell analyses pinpointed hepatocyte-enriched CEBPB as a key epigenetically regulated effector. Luciferase reporter assays, ChIP-qPCR, and gain- and loss-of-function experiments showed that KYN activated the aryl hydrocarbon receptor (AHR), increased H3K27ac enrichment at the Cebpb locus, and induced Cebpb transcription. CEBPB knockdown blocked KYN-induced PI3K-AKT activation and lipid accumulation, whereas in vivo KYN supplementation largely reversed Cur-mediated protection. Collectively, this study reveals a novel gut-liver axis in MASLD pathogenesis, demonstrating that Cur alleviates hepatic steatosis by targeting the microbiota-KYN-AHR-H3K27ac-Cebpb epigenetic axis, positioning Cur supplementation and KYN modulation as promising therapeutic strategies for MASLD intervention.},
}

Animals
*Epigenesis, Genetic/drug effects
*Curcumin/pharmacology/therapeutic use
*Gastrointestinal Microbiome/drug effects
*Fatty Liver/drug therapy/metabolism/genetics
Rats
Male
Liver/metabolism/drug effects/pathology
Diet, High-Fat/adverse effects
Humans
*Non-alcoholic Fatty Liver Disease/drug therapy/metabolism

@article {pmid42887564,
year = {2026},
author = {Stallmach, A and Guse, J and Katzer, K and Reuken, PA and Knafla, F and Schauer, A and Thon, S and Kiehntopf, M and Haziri, D and Steube, A},
title = {Fecal Microbiota Transfer for Recurrent Clostridioides difficile Infection: A Retrospective Single-Center Analysis.},
journal = {Zeitschrift fur Gastroenterologie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2954-8029},
pmid = {42887564},
issn = {1439-7803},
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea. Despite high initial response rates to antibiotic therapy, recurrence occurs in approximately 20% of patients. Fecal microbiota transplantation (FMT) has emerged as an effective treatment option for multiple recurrences, demonstrating high efficacy and a favorable safety profile. This study aimed to evaluate the effectiveness and safety of FMT in patients with recurrent CDI (rCDI).

METHODS: In this single-center retrospective study, 75 patients who underwent FMT for rCDI between November 2016 and January 2026 after experiencing at least two recurrences despite standard antibiotic therapy were included. Donor screening was performed according to the requirements of the German Federal Institute for Drugs and Medical Devices (BfArM). Following CDI-directed antibiotic pretreatment, FMT was administered either by colonoscopy, oral capsules, or a combination of both. Patients were followed for three months. The primary endpoint was the absence of diarrhea as a surrogate marker for rCDI, including a predefined subgroup analysis of patients with inflammatory bowel disease (IBD).

RESULTS: Follow-up data were available for 65 patients, of whom 56 (86.1%) achieved sustained clinical remission. Patients with concomitant IBD (n=15) showed a comparable response rate (86.7%). The route of FMT administration had no significant impact on treatment outcome. Overall, FMT was well tolerated, with only four patients (5.3%) reporting predominantly self-limiting adverse events.

CONCLUSION: FMT is a highly effective and safe treatment for recurrent CDI, including in multimorbid patients and those with concomitant IBD.},
}

@article {pmid42875381,
year = {2026},
author = {Zhu, X and Cheng, L and Li, S and Guo, D and Guo, W and Du, X and Yan, R and Wang, X and Yuan, S and Chen, M and Zhang, W and Li, S and Li, F and Zhang, L},
title = {Fecal microbiota transplantation for the treatment of neurogenic rosacea: protocol of a randomized, blinded, placebo-controlled explorer study.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2735091},
doi = {10.1080/07853890.2026.2735091},
pmid = {42875381},
issn = {1365-2060},
mesh = {Humans ; *Rosacea/therapy/microbiology ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; Female ; Treatment Outcome ; Adult ; Quality of Life ; Male ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Dysbiosis/therapy ; Feces/microbiology ; },
abstract = {INTRODUCTION: Neurogenic rosacea is a distinct phenotype of rosacea characterized by persistent facial erythema, flushing, burning, and stinging, and it often responds poorly to conventional therapies. Increasing evidence suggests that gut microbiota dysbiosis may be involved in the pathogenesis of NR. Fecal microbiota transplantation may provide a novel therapeutic strategy by restoring microbial homeostasis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of FMT in patients with NR and to explore its potential mechanisms through modulation of the gut microbiota.

PATIENTS AND METHODS: This is a single-center, randomized, double-blind, placebo-controlled exploratory trial. Sixty patients with NR will be randomly assigned (1:1) to receive either FMT capsules or placebo capsules for 3 consecutive weeks and followed for 12 weeks. The primary outcome is the proportion of participants achieving CEA success at week 12, defined as a CEA score of 0 or 1 or a reduction of ≥2 grades from baseline. Secondary outcomes include flushing severity, symptom scores, quality of life, psychological status, objective erythema index, and safety. Exploratory analyses will assess gut microbiota composition, fecal and serum metabolomics, and neurovascular-related cytokines.

DISCUSSION: This study is the first clinical trial to explore the effects of fecal microbiota transplantation in the treatment of neurogenic rosacea. The trial may provide clinical evidence for the application of fecal microbiota transplantation as a novel therapeutic strategy for refractory neurogenic rosacea.

TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500109957) on September 28, 2025.},
}

Humans
*Rosacea/therapy/microbiology
Double-Blind Method
*Fecal Microbiota Transplantation/methods
Female
Treatment Outcome
Adult
Quality of Life
Male
*Gastrointestinal Microbiome/physiology
Middle Aged
*Dysbiosis/therapy
Feces/microbiology

@article {pmid42875799,
year = {2026},
author = {He, D and Zhang, HC and Shen, BB and Zhao, D and Tang, XY and Xie, J and Zhou, RR and Zeng, HL and Zhang, SH},
title = {Extract from Eucommia ulmoides Oliv. Leaves alleviates APAP-induced acute liver injury via reshaping gut microbiota and attenuating microbial bile acids metabolism disorder.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {42875799},
issn = {1749-8546},
support = {2025M773945//China Postdoctoral Science Foundation/ ; 2024JJ7292//Natural Science Foundation of Hunan Province/ ; No. 2024JK2120//This work was supported by Hunan Provincial Science and Technology Department Project/ ; 2060302-2304-02//the Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources/ ; },
abstract = {BACKGROUND: Increasing studies suggest that supplementing flavonoids from Eucommia ulmoides Oliv. Leaves (EUL) exerts liver protective effects via reshaping gut microbiota and regulating bile acids (BAs) metabolism. However, the relationship between EUL, gut microbiota and BAs metabolism remains unclear and the potential mechanisms of action has not been expounded clearly.

PURPOSE: To demonstrate the important role of gut microbiota and microbial BAs metabolism in alleviation acetaminophen-induced liver injury (AILI) by EUL.

METHODS: AILI mice model was employed to evaluate the therapeutic efficacy of EUL. The hepatic function was assessed, and biological samples were collected for histopathological examination, bacterial 16S rRNA sequencing analysis, BAs-targeted metabolomics, and the evaluation of the intestinal barrier function. Additionally, antibiotic cocktail-triggered gut microbiota deficiency and fecal microbiome transplantation were investigated to the relationship of molecular mechanistic between the protective efficiency of EUL in AILI, gut microbiota, and the metabolism of microbial BAs.

RESULTS: EUL alleviate liver damage, involving reduction of liver function index, down-regulation of inflammatory cytokines and oxidative stress index, and restoration of pathological changes of liver tissue. EUL also improved intestinal barrier dysfunction and reshaped gut microflora dysbiosis in AILI mice. Moreover, antibiotic cocktail-triggered intestinal microbiota deficiency and fecal microbiome transplantation (FMT) evidenced that the liver protection of EUL was tightly related with gut microbiota. BAs-targeted metabolomics assay demonstrated that EUL mitigated the altered metabolism of microbial BAs during the development of AILI. EUL promoted the abundance of Firmicutes phylum, and elevating the beneficial microbes in Ruminococcaceae and Lachnospiraceae family, which were associated with up-regulated proportion of secondary bile acids (including DCA, NorDCA and 7-ketoLCA), leading to the reduction intestinal inflammation and preservation intestinal integrity. In particular, EUL enriched the beneficial microbes in Lachnoclostridium, Lachnospiraceae_UCG-006, [Eubacterium]_xylanophilum_group, Oscillibacter, Ruminiclostridium, and Desulfovibrio genera. Furthermore, EUL administration increased levels of CDCA, which could activate FXR-FGF15, enabling to decreased synthesis of BAs in the liver and promoting excretion.

CONCLUSIONS: EUL supplementation alleviate AILI by reshaping the dysfunctional gut microbiota and attenuating disordered BAs metabolism, resulting to improvements in BAs enterohepatic circulation and gut barrier function. The mechanism may be closely related to the gut microbiome-BAs-FXR signaling in gut-liver axis.},
}

@article {pmid42875867,
year = {2026},
author = {Zhang, J and Han, K},
title = {Metabolic-Epigenetic Reprogramming of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis: Perspectives for Traditional Chinese Medicine.},
journal = {Immunological investigations},
volume = {},
number = {},
pages = {1-47},
doi = {10.1080/08820139.2026.2747770},
pmid = {42875867},
issn = {1532-4311},
abstract = {BACKGROUND: In rheumatoid arthritis (RA), persistent synovial inflammation and clinical relapse cannot be fully explained by immune activation alone, as fibroblast-like synoviocytes (FLS) can acquire stable pathogenic states that sustain synovitis and joint destruction. Metabolic reprogramming and epigenetic remodeling are functionally integrated in RA-FLS, thereby promoting hyperproliferation, invasiveness, apoptosis resistance, and inflammatory memory.

METHODS AND RESULTS: In this review, we summarize the interplay between altered cellular metabolism and epigeneticmechanisms, including DNA methylation, histone modifications, non-coding RNAs, RNA modifications, and chromatin remodeling, and discuss how this interplay contributes tostabilizing pathogenic FLS phenotypes.We further discuss gut microbiota-associated metabolites, including short-chain fatty acids, bile acids, tryptophan derivatives, and one-carbon metabolites, as potential mediators linking systemic metabolic imbalance to FLS epigenetic states. These metabolites may act through histone deacetylase (HDAC) inhibition, modulation of methyl donor availability, and receptor-mediated inflammatory signaling. From the perspective of Traditional Chinese Medicine (TCM), we propose that TCM formulations and bioactive compounds may modulate this network through microbiota-dependent metabolic remodeling and direct suppression of FLS activation. Finally, we identify current evidence gaps and highlight emerging therapeutic strategies, including metabolomics-guided fecal microbiota transplantation and FLS-targeted epigenetic interventions.

CONCLUSION: This review highlights metabolic-epigenetic reprogramming as a key mechanism underlying persistent RA-FLS phenotypes. Interactions among thegut microbiota, microbial metabolites, and epigenetic regulation provide a promising framework for linking systemic metabolic disturbances to local joint damage. Future studies integrating multi-omics profiling, microbiome modulation, and FLS-targeted epigenetic interventions are needed to clarify causality and facilitate more precise therapeutic strategies.},
}

@article {pmid42876317,
year = {2026},
author = {Wang, X and Wang, L and Liu, Y},
title = {The Role of Gut Microbiota in Chronic Constipation and the Therapeutic Potential of Fecal Microbiota Transplantation.},
journal = {Journal of gastroenterology and hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgh.70807},
pmid = {42876317},
issn = {1440-1746},
abstract = {OBJECTIVE: This study investigates the relationship between gut microbiota dysbiosis and chronic constipation (CC) and evaluates the therapeutic efficacy of fecal microbiota transplantation (FMT) in restoring microbial homeostasis and metabolic function.

METHODS: We retrospectively analyzed existing before-after clinical data from 206 patients with CC who received FMT. No placebo or case-control group was included. Gut microbiota profiles were analyzed before and after FMT using 16S rRNA sequencing. Alpha and beta diversity indices were calculated to assess microbial community evolution. Gas chromatography-mass spectrometry (GC-MS) was employed to quantify short-chain fatty acids (SCFAs). Patients were stratified into butyrate-high and butyrate-low metabolic subtypes using a partitioning around medoids (PAM) algorithm based on pre-transplant butyrate levels. Clinical severity was independently defined using Rome IV criteria, CSBM, BSFS, and PAC-SYM.

RESULTS: FMT significantly increased microbial α-diversity and shifted the community structure toward that of healthy donors. Post-transplant, the Bacteroidetes/Firmicutes ratio decreased from 46.8% to 38.9%, with a marked enrichment of beneficial taxa such as Faecalibacterium, Akkermansia, and Bifidobacterium. These shifts correlated with a significant rise in SCFA concentrations, particularly acetic and butyric acids. Butyrate deficiency was characterized by broader SCFA deficiencies and fragmented microbial networks. Multivariable binary logistic regression identified Faecalibacterium, ACE index, and acetic acid as independent predictors of clinically defined constipation severity.

CONCLUSION: FMT was associated with increased microbial diversity, restoration of SCFA-producing taxa, and increased SCFA concentrations in patients with CC. These changes accompanied improvements in CSBM, BSFS, PAC-SYM, and PAC-QOL.},
}

@article {pmid42876954,
year = {2026},
author = {Negi, P and Upreti, A and Budhlakoti, P and Sen, AK and Danu, M and Tewari, S and Joshi, N and Chandra Joshi, D},
title = {Gut microbiota-cancer crosstalk: emerging molecular targets for personalized cancer treatment- a comprehensive review.},
journal = {Frontiers in molecular biosciences},
volume = {13},
number = {},
pages = {1924197},
pmid = {42876954},
issn = {2296-889X},
abstract = {Cancer remains a major global health challenge, and growing evidence indicates that the gut microbiota plays an important role in cancer initiation, progression, metastasis, and response to treatment through complex interactions with host signaling, metabolism, and immunity. This comprehensive narrative review discusses the molecular mechanisms underlying gut microbiota-cancer crosstalk, with particular emphasis on dysbiosis, microbial metabolites, immune modulation, and microbiota-regulated oncogenic pathways, including TLR/NF-κB, Wnt/β-catenin, JAK/STAT, PI3K/Akt/mTOR, and Hippo-YAP signaling. The review also examines emerging molecular targets, including microbial extracellular vesicles, bacterial small RNAs, ferroptosis-related mechanisms, and microbiota-mitochondria interactions. In addition, current microbiota-targeted therapeutic strategies, such as fecal microbiota transplantation, engineered bacterial therapeutics, CRISPR-based microbiome engineering, and microbiome-informed approaches to precision oncology are discussed. Relevant peer-reviewed literature published primarily within the recent 5-year period was considered from major scientific databases and publisher platforms, including PubMed, Scopus, Web of Science, Springer, Elsevier, and MDPI. Overall, the available evidence suggests that gut microbiota represents an important component of the tumor ecosystem and may provide promising biomarkers and therapeutic targets. Integration of microbiome research with multi-omics and artificial intelligence may further support the development of personalized cancer treatment.},
}

@article {pmid42877054,
year = {2026},
author = {Niu, C and Hua, Y and Kang, J and Li, F and Chen, B and Guo, R and Wei, Y},
title = {Gut Microbiota-Dependent Tryptophan Metabolism Drives the Therapeutic Effects of Baitouweng Tang in Colitis via the AhR Pathway.},
journal = {Food science & nutrition},
volume = {14},
number = {10},
pages = {e72434},
pmid = {42877054},
issn = {2048-7177},
abstract = {With dysregulation of the gut microbiota and its metabolic byproducts playing a pivotal role in inflammatory bowel disease (IBD) pathogenesis. Baitouweng Tang (BTWT), a traditional herbal formulation, has long been employed to treat gastrointestinal disorders and shows promising potential in the management of IBD. However, its precise pharmacological mechanisms remain elusive. In this study, we employed targeted metabolomics, high-throughput sequencing, and molecular biology techniques to elucidate the therapeutic mechanisms of BTWT in the treatment of ulcerative colitis (UC). BTWT significantly enhanced the relative abundance of Bifidobacterium, improved the indole metabolic pathway of tryptophan, and restored the levels of indole metabolites, such as indole-3-lactic acid (ILA). These changes activated the aryl hydrocarbon receptor (AhR) and led to marked improvements in the clinical symptoms of UC in mice. Conversely, the therapeutic effects of BTWT were substantially diminished in an antibiotic-induced gut microbiota depletion model. Notably, fecal microbiota transplantation (FMT) partially restored BTWT efficacy, underscoring the critical role of the gut microbiota in mediating its therapeutic effects. Furthermore, in an in vitro lipoteichoic acid (LTA)-induced HT-29 inflammation model, ILA treatment attenuated inflammation and concurrently increased the expression of AhR, CYP1A1, and CYP1B1. These findings suggest a potential link between BTWT-induced changes in tryptophan metabolites, AhR pathway activation, and the amelioration of colitis, though the causal relationship remains to be established. Our study provides a basis for further mechanistic investigation into the AhR pathway as a possible therapeutic target in UC.},
}

@article {pmid42877110,
year = {2026},
author = {Chen, G and Li, J and Huang, T and Zeng, D and Mo, L and Li, J and Zhu, C},
title = {Gut microbiota in genetic diseases: from Mendelian disorders to complex traits.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1908644},
pmid = {42877110},
issn = {1664-3224},
mesh = {Humans ; *Genetic Diseases, Inborn/microbiology/genetics/etiology/immunology ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/microbiology/immunology ; Animals ; Phenotype ; },
abstract = {As a core component of the human microecosystem, the dynamic balance of the composition and function of gut microbiota is essential to host health. In recent years, numerous studies have demonstrated that gut dysbiosis is not only associated with metabolic diseases and immune disorders but also plays a pivotal role in the pathogenesis of hereditary diseases. Ranging from chromosomal diseases (e.g., Down syndrome), monogenic diseases (e.g., cystic fibrosis, phenylketonuria, familial adenomatous polyposis, hereditary hemolytic anemia), mitochondrial diseases (e.g., Leber's hereditary optic neuropathy, mitochondrial encephalomyopathy) to polygenic hereditary diseases (e.g., inflammatory bowel disease, autism spectrum disorder, obesity and diabetes), gut microbiota can markedly alter the manifestation and severity of disease phenotypes by regulating host immune responses, metabolic pathways and gene expression. Nevertheless, the bidirectional interaction network between host genes and gut microbiota has not been fully elucidated. Most existing studies merely focus on correlation analysis, and in-depth exploration of causal mechanisms remains insufficient. This review elaborates on the mechanisms of gut microbiota in monogenic diseases and hereditary diseases with complex phenotypes. By integrating the latest advances in genomics, metabolomics and microbiomics, it discusses how gut dysbiosis affects disease progression via immune modulation, metabolite reprogramming and epigenetic modification. Meanwhile, this paper summarizes the current status and challenges of clinical translation of microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation(FMT), in the treatment of hereditary diseases. This review aims to provide a microecological perspective for understanding the pathogenesis of hereditary diseases and offer theoretical support for personalized and precise intervention.},
}

Humans
*Genetic Diseases, Inborn/microbiology/genetics/etiology/immunology
*Gastrointestinal Microbiome/immunology
*Dysbiosis/microbiology/immunology
Animals
Phenotype

@article {pmid42879046,
year = {2026},
author = {Ahmed, LA and Al-Massri, KF},
title = {Gut Microbiota Modulation in CNS Disorders: Therapeutic Strategies and Implications for Drug Efficacy.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42879046},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Central Nervous System Diseases/microbiology/drug therapy/therapy ; *Gastrointestinal Microbiome/drug effects/physiology ; Probiotics/therapeutic use ; Treatment Outcome ; },
abstract = {Various central nervous system (CNS) disorders, including neurodegenerative diseases, depression, schizophrenia, epilepsy, and anxiety, present significant obstacles to public health because of their intricate causes and the scarcity of effective treatments. Recent studies have shown that gut microbiota (GM) and CNS communicate bidirectionally. Modulation of immune system, neurotransmitters, and neuroactive metabolites are only a few examples of how GM can significantly influence CNS. Dysbiosis or changes in composition and function of gut microbes play a contributing role in various CNS disorders. In these disorders, probiotics, prebiotics, fecal microbiota transplantation, antibiotics use, and interventions based on microbial metabolites have demonstrated beneficial effects in animal models and some clinical studies. By restoring microbial equilibrium, increasing microbial diversity, and promoting the generation of beneficial metabolites, these approaches can improve the efficacy of traditional medications while minimizing their side effects and the disease itself, based on preclinical evidence and emerging clinical studies. Nevertheless, several obstacles should be overcome before the clinical translation of these approaches, such as using of standardized methods for modulating GM, identifying specific microbial signatures linked to various CNS illnesses, and understanding the exact mechanisms of gut-brain communication. This review provides a novel integrated perspective by comprehensively clarifying the bidirectional interactions between CNS pharmacological agents and microbiota-based therapeutic strategies in different neurological and psychiatric disorders, offering a unified framework to improve traditional pharmacological therapies. Importantly, future studies should concentrate on exploring the mechanisms and the exact interconnections between GM and CNS problems to elaborate targeted therapies for these disorders.},
}

Humans
Animals
*Central Nervous System Diseases/microbiology/drug therapy/therapy
*Gastrointestinal Microbiome/drug effects/physiology
Probiotics/therapeutic use
Treatment Outcome

@article {pmid42879156,
year = {2026},
author = {Diefenhardt, M and Fokas, E and Kosmala, R and Polat, B and Germer, CT and Schlenska-Lange, A and Kuhnt, T and Ghadimi, M and Rieken, S and Wiegering, A and Schwarzbach, M and Fleischmann, M and Grützmann, R and Ott, OJ and Martus, P and Königsrainer, A and Zips, D and Hofheinz, RD and Gani, C and Rödel, C},
title = {Organ Preservation and Quality of Life After Total Neoadjuvant Treatment in Rectal Cancer.},
journal = {JAMA network open},
volume = {9},
number = {10},
pages = {e2639063},
doi = {10.1001/jamanetworkopen.2026.39063},
pmid = {42879156},
issn = {2574-3805},
mesh = {Humans ; *Quality of Life ; *Rectal Neoplasms/therapy/psychology/surgery ; Male ; *Neoadjuvant Therapy/methods ; Female ; Middle Aged ; Aged ; *Adenocarcinoma/therapy ; Watchful Waiting ; Germany ; Cohort Studies ; *Organ Preservation ; },
abstract = {IMPORTANCE: Data on quality of life (QOL) after total neoadjuvant therapy (TNT) are important for counseling patients on the benefits of watch-and-wait (WW) vs total mesorectal excision (TME) for rectal cancer. A thorough understanding of both options and their long-term impact on bowel, urinary, sexual function, and other QOL domains remains limited.

OBJECTIVE: To examine the association of organ preservation with QOL and functional outcomes among patients with rectal cancer treated in 2 phase 2 clinical trials.

This unplanned, post hoc, cohort study used data from the CAO/ARO/AIO-12 and CAO/ARO/AIO-16 trials, recruiting participants from June 15, 2015, through October 7, 2020, from 19 centers in Germany. Included patients had cT3 to cT4 or node-positive rectal adenocarcinoma. Total neoadjuvant treatment included chemoradiation therapy combined with induction or consolidation chemotherapy. The statistical analysis was performed from March 6 to December 23, 2025.

MAIN OUTCOMES AND MEASURES: The association of WW with functional outcomes and QOL was assessed using prospectively recorded EORTC QLQ-C30, EORTC QLQ-CR29, and Wexner score questionnaires. Differences in QOL scores were estimated using adjusted longitudinal and cross-sectional analyses with a predefined clinically meaningful difference of at least 5 points.

RESULTS: Baseline questionnaires were available from 346 of 385 eligible patients (89.9%; median [range] age, 60 [19-80] years; 257 male [67%]), while available QOL questionnaires decreased over time to 185 (48.1%) at 5 years. Using the longitudinal analytic approach, statistically significant and clinically meaningful differences in favor of WW were noted for fecal incontinence (-21.2 [95% CI, -30.0 to -12.3]; P < .001); stool frequency (-19.8 [95% CI, -27.6 to -11.9]; P < .001); embarrassment (-17.0 [95% CI, -27.4 to -6.6]; P = .002); flatulence (-15.2 [95% CI, -24.4 to -6.0]; P < .001), buttock pain (-11.9 [95% CI, -20.8 to -3.0]; P = .01); social (9.7 [95% CI, 1.1-18.3]; P = .03), physical (10.2 [95% CI, 4.1-16.3]; P = .002), and role (13.9 [95% CI, 4.9-22.9]; P = .003) functioning; and global health status (9.2 [95% CI, 3.2-15.2]; P = .004). These clinically meaningful differences were detectable in both the intended organ preservation and disease-free groups. Patients with sustained clinical complete response at 3 years (n = 29) vs those with pathologic complete response or matched baseline characteristics favored WW for fecal incontinence (-24.0 and -11.6, respectively), stool frequency (-34.6 and -19.1), sore skin (-18.0 and -18.1), buttock pain (-14.7 and -17.6), embarrassment (-41.1 and -20.5), role functioning (19.1 and 10.9), and social functioning (20.0 and 8.4).

CONCLUSIONS AND RELEVANCE: In the absence of prospective randomized trials, this study provides evidence suggesting long-term clinically meaningful benefits for organ preservation regarding QOL, especially for most gastrointestinal subscales, social functioning, and global health status, over a 5-year period among patients with rectal cancer. As treatment options for patients with rectal cancer now routinely include WW in cases of clinical complete response after TNT, patient-reported QOL measures have become paramount for informed shared decision-making.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02363374 and NCT03561142.},
}

Humans
*Quality of Life
*Rectal Neoplasms/therapy/psychology/surgery
Male
*Neoadjuvant Therapy/methods
Female
Middle Aged
Aged
*Adenocarcinoma/therapy
Watchful Waiting
Germany
Cohort Studies
*Organ Preservation

@article {pmid42879923,
year = {2026},
author = {Chen, X and Zhao, X and Zheng, J and Jiang, J and Wu, F},
title = {Low-dose triclosan induces neurotoxicity in zebrafish via gut microbiota disruption.},
journal = {Journal of hazardous materials},
volume = {518},
number = {},
pages = {143683},
doi = {10.1016/j.jhazmat.2026.143683},
pmid = {42879923},
issn = {1873-3336},
abstract = {Triclosan (TCS), a broad-spectrum antibacterial agent, is widely detected in environmental and human samples, yet its neurotoxic risks and mechanisms following long-term environmental exposure remain unclear-particularly the role of gut microbiota. Using germ-free zebrafish and fecal microbiota transplantation, we established a causal link between TCS-induced gut dysbiosis and neurotoxicity. Integrating transcriptomics, 16S rRNA sequencing, and gut-derived metabolite transplantation, we elucidated the underlying molecular mechanisms. Three-month exposure to environmentally relevant TCS concentrations significantly enriched gut Proteobacteria, increasing lipopolysaccharide (LPS) levels. LPS subsequently crossed the damaged blood-brain barrier via the gut-brain axis, triggering neuroinflammation and behavioral abnormalities in female zebrafish. Notably, TCS exhibited dose-dependent neurotoxicity: low doses (0.4 and 4.0 μg/L) acted primarily through gut microbiota disruption, while high-dose (40 μg/L) effects involved both microbiota-dependent and independent pathways. This study provides new insights into the neurotoxic mechanisms of TCS and highlights the critical role of gut microbiota in mediating its effects. However, this study was conducted exclusively in female zebrafish, and further investigations in males are warranted to assess potential sex differences.},
}

@article {pmid42868115,
year = {2026},
author = {Qian, X and Shen, Y and Luo, X and Zhang, S and Wang, L and He, H and Wang, B},
title = {Adult-sourced fecal microbiota transplantation ameliorates early-life antibiotic-induced intestinal immune stress in juvenile mice associated with the modulation of the TLR4/MyD88 signaling pathway.},
journal = {PloS one},
volume = {21},
number = {10},
pages = {e0359634},
pmid = {42868115},
issn = {1932-6203},
mesh = {Animals ; *Fecal Microbiota Transplantation ; *Toll-Like Receptor 4/metabolism ; *Myeloid Differentiation Factor 88/metabolism ; *Signal Transduction/drug effects ; *Anti-Bacterial Agents/adverse effects/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects/immunology ; *Intestines/immunology/microbiology/drug effects ; Male ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Bacteroides ; Dysbiosis/therapy/chemically induced/immunology ; Intestinal Mucosa/immunology/microbiology ; Interleukin-22 ; },
abstract = {Early-life antibiotic (ABX) exposure profoundly disrupts gut microbiota assembly, triggering long-lasting intestinal immune stress. While fecal microbiota transplantation (FMT) is a promising intervention, its immunological and ecological mechanisms in the juvenile gut remain underexplored. In this study, juvenile mice were subjected to a broad-spectrum ABX cocktail for 8 days followed by 4 days of adult-sourced FMT. 16S rRNA sequencing (n = 6/group) revealed that ABX drastically altered the microbial landscape, causing a severe relative reduction of core commensals and an opportunistic expansion of Bacteroides. Subsequent molecular analyses on day 13 (n = 3/group) demonstrated that this dysbiosis significantly upregulated the mucosal TLR4/MyD88 signaling axis and effector cytokines IL-17 and IL-22. Strikingly, adult FMT administration effectively attenuated the TLR4 cascade and reduced pro-inflammatory cytokine transcript levels while immunoregulatory IL-10 transcripts remained partially elevated. Ecologically, FMT did not merely revert the gut to its naive juvenile baseline. Instead, it suppressed Bacteroides overgrowth and established a distinctly new, highly complex community enriched with putative mature, adult-signature taxa such as Parabacteroides, Tannerellaceae, and Desulfobacterota. Interestingly, the downregulation of TLR4 occurred concurrently with the engraftment of these Gram-negative, LPS-bearing taxa. Collectively, adult-sourced FMT ameliorates ABX-induced immune stress not by restoring the original microbiota, but by driving the juvenile gut towards a putatively mature, structurally distinct, and potentially immunologically tolerant ecological state.},
}

Animals
*Fecal Microbiota Transplantation
*Toll-Like Receptor 4/metabolism
*Myeloid Differentiation Factor 88/metabolism
*Signal Transduction/drug effects
*Anti-Bacterial Agents/adverse effects/pharmacology
Mice
*Gastrointestinal Microbiome/drug effects/immunology
*Intestines/immunology/microbiology/drug effects
Male
RNA, Ribosomal, 16S/genetics
Mice, Inbred C57BL
Bacteroides
Dysbiosis/therapy/chemically induced/immunology
Intestinal Mucosa/immunology/microbiology
Interleukin-22

@article {pmid42871658,
year = {2026},
author = {Liu, W and Lan, Y and Chen, X and Wei, H and Zhang, T and Wang, Y},
title = {Deciphering the gut-liver axis in MASLD: from dysbiosis-driven pathogenesis to precision microbiome therapeutics.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1971785},
pmid = {42871658},
issn = {1664-302X},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disorder worldwide, characterized by a multifactorial pathogenesis involving genetic predisposition, metabolic disturbances, environmental influences, and gut microbiota interactions. In recent years, the gut microbiota has garnered significant attention for its pivotal role in MASLD development and progression through the gut-liver axis. This review comprehensively summarizes current understanding of the molecular mechanisms by which gut microbiota and their metabolites contribute to MASLD pathogenesis, including intestinal barrier dysfunction, bile acid metabolism dysregulation, abnormalities in short-chain fatty acid and tryptophan metabolism, oxidative stress, and mitochondrial impairment. Furthermore, we comprehensively discuss advances in therapeutic strategies targeting gut microbiota modulation, such as probiotics/prebiotics, fecal microbiota transplantation, dietary interventions, bioactive compounds from traditional Chinese medicine, and surgical approaches. By integrating these insights, this review aims to provide novel perspectives for precise prevention and treatment of MASLD, highlighting the gut microbiota as a promising target for future clinical management.},
}

@article {pmid42871751,
year = {2026},
author = {Villafuerte-Gálvez, JA and Noriega, MA and Cakir Colak, S and Crawford, CV},
title = {The Patients' Voice in Clostridioides difficile Infection: Large Language Model-Assisted Thematic Analysis of Patient Testimonials.},
journal = {Open forum infectious diseases},
volume = {13},
number = {10},
pages = {ofag650},
pmid = {42871751},
issn = {2328-8957},
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) imposes a burden that extends well beyond the gastrointestinal tract, yet existing outcome measures only partially capture the patient experience. We used frontier large language models (LLMs) on patient and caregiver narratives at scale to describe how burden shifts with disease course.

METHODS: We analyzed 189 testimonials from the Peggy Lillis Foundation corpus, sorted into 4 cohorts with recurrence (r) and fulminant (f) severity as axes (rfCDI, fCDI, rCDI, non-rfCDI). Two independent LLMs coded 8 thematic domains, 4 fulminant flags, 13 emerging semantic fields, the dominant dimension, and narrative arcs. Two physicians independently coded a subset for inter-rater reliability (PABAK, Gwet's AC1).

RESULTS: Treatment trajectory was the dominant theme in recurrent disease, whereas death and near-death dominated nonrecurrent fulminant narratives. Psychological burden was near-universal in fulminant disease (98.0% in rfCDI, 97.2% in fCDI). Caregiver and bereavement content concentrated in fCDI (66.7%). Diagnostic failure was frequent across recurrent cohorts (47.6-56.1%). Mentions of bacteriotherapy (fecal microbiota transplantation) concentrated in recurrent cohorts (60.2% rfCDI versus 5.6% fCDI). Financial, mental-health, and caregiver burdens were prominent and remain largely unaddressed by guidelines. Human-human reliability was substantial (PABAK 0.79 for semantic fields, 0.76 for domains); arc coding was least reliable.

CONCLUSIONS: Patient narratives reveal a course-dependent, multidimensional burden in CDI. Concrete gaps exist between what patients prioritize, what guidelines recommend, and what therapy access provides. Frontier-LLM coding, validated against clinicians, offers a reproducible route to translate these priorities into research, care, and policy.},
}

@article {pmid42871959,
year = {2026},
author = {Wu, Q and Li, C and Song, S and Wang, H and Zhao, R and Sun, L and Shang, B and Geng, Y},
title = {Maternal Diglyceride Diet Attenuates Selected Metabolic Effects of Maternal High-Fat Feeding in Offspring via Energy Metabolism and Microbiota Modulation.},
journal = {Food science & nutrition},
volume = {14},
number = {10},
pages = {e72427},
pmid = {42871959},
issn = {2048-7177},
abstract = {Diglyceride (DAG) has been shown to improve obesity in animals, but its effects on mothers and offspring were unclear. This study investigated whether maternal DAG intake affects male offspring by mating female C57BL/6J mice on a DAG diet with normal males. Male offspring were weaned at 3 weeks, with some euthanized and others fed normal, high-fat (HFD), or DAG diets for 9 weeks. Results showed that offspring from DAG-fed mothers had lower blood lipids than those from HFD-fed mothers, and maternal DAG intake was associated with restoration of purine/pyrimidine metabolism while altering gut microbiota (lower Firmicutes/Bacteroidetes ratio, higher butyrate). Fecal transplants confirmed DAG partially reversed HFD-induced gut dysbiosis. Although DAG mitigated maternal obesity effects, post-weaning diet had a stronger influence, suggesting DAG oil may help prevent intergenerational obesity transmission.},
}

@article {pmid42873094,
year = {2026},
author = {Pizzi, A and Creta, E and Pallozzi, M and Stella, L and Gasbarrini, A and Ponziani, FR and Cerrito, L},
title = {Gut microbiota-considered pharmacotherapeutic management of hepatocellular carcinoma.},
journal = {Expert opinion on pharmacotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14656566.2026.2749646},
pmid = {42873094},
issn = {1744-7666},
abstract = {INTRODUCTION: Treatment efficacy for hepatocellular carcinoma (HCC) remains limited. Increasing evidence indicates that gut microbiota may influence treatment response, toxicity and clinical outcomes.

AREAS COVERED: Our review synthesizes recent literature from PubMed and Wiley Online Library regarding gut microbiota, microbial metabolites, HCC and immunotherapy by critically analyzing the main research frameworks and identifying current research gaps. Clinical studies suggest that microbial diversity and specific taxa, including Akkermansia, Bifidobacterium, Faecalibacterium, and Ruminococcus may be associated with improved responses to immune checkpoint inhibitors (ICIs). Microbiota-targeted approaches, including fecal microbiota transplantation (FMT), probiotics, engineered bacteria, dietary interventions, selective antimicrobial strategies, and postbiotics, are biologically promising but remain experimental in HCC.

EXPERT OPINION: Despite the encouraging results about the modulation of ICIs response by FMT in other solid tumors (melanoma, colorectal cancer, renal cell carcinoma and mixed solid-tumor), whether this strategy is effective and safe in HCC remains to be established in prospective HCC-specific trials. The availability of a preliminary detailed characterization of gut microbial before undertaking HCC treatment would be tempting, especially if it could lead to a more precision-tailored approach with the possibility to foresee, within certain limits, the therapeutic outcome. Moreover, the eventual discovery of specific bacterial patterns in responders and non-responders to ICIs could open the possibility to administer FMT as a standard of care at least in selected patients with the target of re-stablishing HCC response to ICIs.},
}

@article {pmid42874318,
year = {2026},
author = {Zimmermann, DM and Diamantino, D and Andrade, SO and Julio, PR and Appenzeller, S},
title = {The gastrointestinal pathway leading to autoimmune diseases.},
journal = {Current opinion in immunology},
volume = {103},
number = {},
pages = {102856},
doi = {10.1016/j.coi.2026.102856},
pmid = {42874318},
issn = {1879-0372},
abstract = {The gut microbiota are important in maintaining immune homeostasis through complex interactions with both innate and adaptive immune systems. Disruptions in microbial composition, referred to as dysbiosis, have been increasingly associated with the development and progression of autoimmune diseases. This review explores the key gastrointestinal pathways linking microbiota alterations to immune dysregulation, emphasizing mechanisms that operate from extracellular barrier function to intracellular signaling cascades. Critical processes include impairment of intestinal barrier integrity, modulation of neuroimmune communication via the enteric nervous system and vagus nerve, and the activation of immune responses through molecular mimicry. In addition, pattern recognition receptors, particularly Toll-like receptors, act as essential mediators of host-microbe interactions, integrating microbial signals into pro- or anti-inflammatory immune pathways. These interconnected mechanisms contribute to chronic inflammation, loss of immune tolerance, and systemic autoimmune responses. Emerging evidence highlights the therapeutic potential of targeting the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation, as well as through modulation of microbial metabolites and immune signaling pathways. A deeper understanding of these host-microbiota interactions may enable the development of novel, microbiota-directed strategies for the prevention and treatment of autoimmune diseases.},
}

@article {pmid42874908,
year = {2026},
author = {Tan, Z and Zeng, J and Huang, F and Gao, F and Hu, Y and Guo, L and Guo, P and Chen, L},
title = {Gut Microbiota-Derived Short-Chain Fatty Acids Mediate the Bone-Protective Effects of Metformin Against Postmenopausal Osteoporosis.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {179442},
doi = {10.1016/j.ejphar.2026.179442},
pmid = {42874908},
issn = {1879-0712},
abstract = {BACKGROUND: Dysbiosis-induced inflammation has been implicated in postmenopausal osteoporosis (PMOP). Although metformin has shown benefits for bone health, the exact role of the gut microbiota in the mechanism underlying this relationship remains unclear.

HYPOTHESIS/PURPOSE: We hypothesised that metformin could alleviate systemic inflammation in PMOP by augmenting the synthesis of short-chain fatty acids (SCFAs) by gut microbes.

METHODS: Micro-computed tomography (μCT) was used to analyse the femurs. Faecal samples were collected for 16S rRNA sequencing and SCFAs detection. Quantitative real-time PCR (qRT-PCR) and western blotting were used to detect mRNA and protein expression, respectively. Primary bone marrow mesenchymal stem cells (BMSCs) and bone marrow macrophages (BMMs) were isolated to explore the effects of SCFAs on bone cell activity following inflammatory stimulation.

RESULTS: Metformin improved trabecular bone microarchitecture in OVX mice, as shown by higher BV/TV, Tb.Th, and Tb.N, and reduced serum and tibial IL-1β and TNF-α. Metformin also increased the abundance of SCFA-producing genera, including Butyricimonas, Prevotella, Ruminococcus, Coprococcus, Oscillospira, and Sutterella, and elevated faecal propionate, butyrate, and valerate. Transplantation of metformin-adapted microbiota reproduced the bone-protective and anti-inflammatory effects, whereas GPR41/GPR43 deficiency abolished the benefits of metformin, propionate, and butyrate. In vitro, propionate and butyrate, but not valerate, promoted BMSC osteogenic differentiation and inhibited BMM-derived osteoclast differentiation under IL-1β/TNF-α-induced inflammation.

CONCLUSIONS: Metformin modulates the gut microbiota by increasing propionate and butyrate synthesis, thereby reducing dysbiosis-induced inflammation and regulating BMSC and BMM differentiation to protect against PMOP.},
}

@article {pmid42874932,
year = {2026},
author = {Chen, L and Tayier, N and Wu, H and Liu, G and Wang, S and Zhu, Y and Sun, J and Niu, Y and Feng, C and You, L and Hu, G and Cao, X and Liu, H and Zhu, M},
title = {Scalable cultured gut microbiota-derived nanovesicles for oral augmentation of checkpoint blockade therapy.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115456},
doi = {10.1016/j.jconrel.2026.115456},
pmid = {42874932},
issn = {1873-4995},
abstract = {Microbiota-targeted strategies, such as fecal microbiota transplantation (FMT), hold promise for enhancing immunotherapy but face clinical challenges including safety risks, batch-to-batch variability, and dependence on substantial quantities of donor fecal material. To overcome these limitations, we established a standardized in vitro expansion platform for responder patient-derived gut microbiota. Through optimization of culture conditions, we achieved stable viability and retention of key immunotherapy-enhancing strains over serial passages, enabling a scalable 6.4 × 10[7]-fold expansion. Leveraging this platform, we engineered hybrid nanovesicles derived from bacterial protoplasts, followed by silica surface coating (HNVs@Silica) for oral delivery. The silica shell significantly improved nanovesicle stability under gastrointestinal conditions and conferred superior antitumor efficacy compared with uncoated counterparts. Notably, HNVs@Silica produced from the 2nd, 4th, and 6th passages retained comparable potency in augmenting anti-PD-1 (αPD-1) therapy. Mechanistically, HNVs@Silica remodeled intestinal immunity, particularly within Peyer's patches, by activating and expanding effector CD8[+] T cells. This local response enhanced the priming and systemic dissemination of tumor-specific T cells, thereby improving the efficacy of αPD-1. Collectively, our findings establish a safe, scalable, and orally bioavailable alternative to FMT for enhancing cancer immunotherapy.},
}

@article {pmid42861983,
year = {2026},
author = {Kutyłowski, K and Alster, P and Madetko-Alster, N},
title = {The link between inflammation and autonomic dysfunction in alpha-synucleinopathies - narrative review.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.112453},
pmid = {42861983},
issn = {0028-3843},
abstract = {INTRODUCTION: Alpha-synucleinopathies are a group of disorders characterized by the accumulation of the pathological form of alpha-synuclein. This group comprises Parkinson's disease, Parkinson's disease dementia, multiple system atrophy, dementia with Lewy bodies, pure autonomic failure, and idiopathic REM sleep behavior disorder. Despite sharing a similar molecular basis, these disorders differ in their clinical presentation. Characteristic manifestations include signs of autonomic failure such as orthostatic hypotension, postural orthostatic tachycardia syndrome, constipation, gastroparesis, urinary incontinence, and erectile dysfunction, among others. These symptoms significantly impair patients' daily functioning and are also negative prognostic factors.

STATE OF THE ART: Currently, research is investigating the link between inflammation and dysautonomic symptoms. Elevated levels of pro-inflammatory cytokines, such as IFN-γ, TNF-α, IL-6, IL-1β, and IFN-α, have been found to accompany these symptoms. Notably, in other diseases characterized by chronic inflammation, autonomic dysfunction is also common.

CLINICAL IMPLICATIONS: In two human studies of dysautonomic symptoms in other conditions, intravenous immunoglobulin therapy was shown to improve these symptoms. Animal studies have shown that other immunomodulatory agents reduce symptom severity.

FUTURE DIRECTIONS: Modulation of inflammation, dietary modification, the use of probiotics and prebiotics, and fecal microbiota transplantation are potential therapeutic approaches for these diseases. These approaches offer hope for improving the quality of life of patients with alpha-synucleinopathies. Further research in this area is needed.},
}

@article {pmid42864919,
year = {2026},
author = {Hu, Y and Wei, T and Wang, S and Yang, Y and Yang, L and Chu, H},
title = {The Role and Mechanisms of Gut Microbiota in the Progression of Hepatic Encephalopathy.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X513988260915065036},
pmid = {42864919},
issn = {1875-6190},
abstract = {Hepatic encephalopathy (HE) is a severe complication of end-stage liver disease that is associated with high mortality; however, its therapeutic options remain limited. The traditional mechanistic understanding focuses on ammonia neurotoxicity, although intestinal bacteria also play a significant role through the gut-liver-brain axis. This review primarily discusses the characteristics of gut dysbiosis in HE, which is marked by a progressive loss of beneficial commensals (e.g., Lachnospiraceae, Ruminococcaceae, and Faecalibacterium) and an overgrowth of potentially pathogenic bacteria (e.g., Enterobacteriaceae, Streptococcaceae, and Veillonellaceae). Unlike previous reviews which have largely focused on phylum- or genus-level changes, this review provides a species-level synthesis of gut microbial alterations in HE. We further summarise the multifaceted mechanisms by which the gut microbiota contributes to HE pathogenesis, including the impairment of intestinal barrier integrity, activation of systemic and neuroinflammation, alterations in microbial metabolites (such as ammonia, short-chain fatty acids, bile acids, and aromatic amino acids), and disruption of neuroendocrine signalling pathways. Furthermore, herein we summarise the microbiota-targeted intervention measures for HE, including aetiological treatments, drug therapies (lactulose and rifaximin), live microbial therapies (probiotics, prebiotics, synbiotics, faecal microbiota transplantation, etc.), and dietary adjustments. Emerging approaches, such as engineered bacteria and phage therapy, are also discussed, along with the barriers to their clinical translation and safety considerations. In summary, targeting the gut microbiota offers a new approach for the precise treatment of HE, although challenges remain in translating these findings into routine clinical practice.},
}

@article {pmid42864924,
year = {2026},
author = {Suresh, N and Singh, V and Rathore, A and Dwivedi, S and Bansal, A},
title = {The Gut Microbiota-inflammation-immune Axis in Cancer: Anti-inflammatory Mechanisms and Therapeutic Implications.},
journal = {Anti-inflammatory & anti-allergy agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715230502786261001104534},
pmid = {42864924},
issn = {1875-614X},
abstract = {Through its mediation between inflammatory and immune pathways, the gut microbiota has proved to be a key regulator of cancer development, progression, and treatment response. Changes in microbial composition known as dysbiosis might facilitate chronic inflammation, immune dysregulation, and genomic instability, thereby facilitating carcinogenesis. Conversely, positive commensal microbes can generate short-chain fatty acids, bile acids, and tryptophan derivatives, which help maintain the epithelial barrier, cytokine signaling, and innate and adaptive immune responses. These microbial metabolites regulate immune cell differentiation, including regulatory T cells, dendritic cells, macrophages, and cytotoxic CD8+ T cells, thereby impacting the tumor microenvironment and tumor progression. Recent research highlights the microbiota as an outcome of response to cancer therapies, particularly immune checkpoint inhibitors, chemotherapy, and targeted therapies. Certain microbial genera, e.g., Akkermansia muciniphila, Bifidobacterium species, and Faecalibacterium prausnitzii, have been linked to augmented antitumor immunity and treatment efficacy. To enhance treatment outcomes and minimize toxicity during therapy, therapeutic interventions that target the regulation of the gut microbiome, such as dietary interventions, probiotics, prebiotics, fecal microbiota transplantation, and engineered microbial platforms, are under investigation. Moreover, improvements in metagenomics, metabolomics, and immunomics are now enabling the discovery of microbiome-based biomarkers to inform precision oncology. Knowledge of the gut microbiota-inflammation-immune axis thus presents promising possibilities in creating new treatment modalities and in designing individualized treatments in cancer management.},
}

@article {pmid42865601,
year = {2026},
author = {Ma, G and Deng, S},
title = {Research progress on intestinal probiotics-mediated protection of the intestinal mucosal barrier in ulcerative colitis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1943748},
pmid = {42865601},
issn = {1664-3224},
mesh = {Humans ; *Probiotics/therapeutic use ; *Colitis, Ulcerative/microbiology/therapy/immunology/metabolism ; Intestinal Barrier Function ; *Intestinal Mucosa/immunology/microbiology/metabolism ; Animals ; *Gastrointestinal Microbiome ; Immunity, Mucosal ; },
abstract = {Ulcerative colitis (UC) is a major subtype of inflammatory bowel disease characterized by a chronic, relapsing course. Its pathogenesis involves complex interactions among gut microbial dysbiosis, epithelial barrier disruption, dysregulated immune responses, and oxidative stress. Impairment of the intestinal mucosal barrier facilitates the translocation of luminal antigens, bacteria, and microbial metabolites into the mucosa, thereby aggravating local inflammation. Probiotics may help maintain barrier homeostasis by reshaping the gut microbial community, reinforcing epithelial and mucus barriers, modulating mucosal immunity, and reducing oxidative injury. This review summarizes recent evidence on the protective effects of probiotics, including Lactobacillus spp., Bifidobacterium spp., and Akkermansia muciniphila, on the intestinal mucosal barrier in UC. Current findings suggest that probiotics can inhibit pathogen adhesion and colonization, enhance the production of beneficial metabolites such as short-chain fatty acids and tryptophan-derived compounds, and promote the expression of tight-junction proteins, including ZO-1, occludin, claudin-1, and claudin-4, as well as mucins such as MUC1 and MUC2. These effects may be mediated through the regulation of NF-κB, NLRP3, aryl hydrocarbon receptor (AhR), mitogen-activated protein kinase (MAPK), and related signaling pathways, thereby attenuating inflammation and oxidative stress and promoting epithelial repair. Combination strategies involving probiotics and prebiotics, traditional Chinese medicine-derived components, postbiotics, fecal microbiota transplantation, or novel delivery systems may improve microbial engraftment, enhance colon-targeted delivery, and strengthen microbiota remodeling and barrier repair. Nevertheless, the available evidence remains limited by substantial strain specificity, insufficient clinical validation, and the absence of standardized intervention protocols. Further multi-omics studies and well-designed clinical trials are warranted to clarify the efficacy, mechanisms, optimal dosing, and safety of these interventions in UC.},
}

Humans
*Probiotics/therapeutic use
*Colitis, Ulcerative/microbiology/therapy/immunology/metabolism
Intestinal Barrier Function
*Intestinal Mucosa/immunology/microbiology/metabolism
Animals
*Gastrointestinal Microbiome
Immunity, Mucosal

@article {pmid42866850,
year = {2026},
author = {Gu, L and Chen, Y and Jin, L and Liu, Y},
title = {A narrative review of the gut microbiota-testis axis: mechanisms and implications for male reproductive health.},
journal = {Translational andrology and urology},
volume = {15},
number = {9},
pages = {350},
pmid = {42866850},
issn = {2223-4691},
abstract = {BACKGROUND AND OBJECTIVE: Infertility affects approximately 8-12% of couples worldwide, with male factors accounting for nearly half of all cases. The gut microbiota is widely recognized as a key regulator of host physiology, yet its specific role in male reproductive health remains to be elucidated. This narrative review synthesizes current evidence on the "gut microbiota-testis axis" and provides a critical evaluation of the strength of evidence derived from different study designs.

METHODS: We conducted a comprehensive literature search in PubMed/MEDLINE up to May 2026 using Boolean search strategies combining terms related to the gut microbiota (e.g., "Gastrointestinal Microbiome", "gut microbiota", "gut microbiome") with terms related to male reproduction (e.g., "Semen Analysis", "Spermatozoa", "Infertility, Male", "semen quality", "sperm quality"). Separate search strategies were developed for human and animal studies. Literature screening and data extraction were performed independently by two reviewers according to predefined inclusion and exclusion criteria.

KEY CONTENT AND FINDINGS: Although human studies remain preliminary, several genera, including Anaerotruncus, Bacteroides, and Faecalibacterium prausnitzii, have been reproducibly associated with semen quality, with microbial metabolites such as butyrate, trimethylamine-N-oxide (TMAO), and succinate potentially serving as important mediators. At the mechanistic level, microbiota-derived metabolic and inflammatory signals act on Leydig cells, Sertoli cells, and germ cells, thereby influencing testosterone synthesis and spermatogenesis. Fecal microbiota transplantation (FMT) experiments in animal models have provided direct evidence for these causal links.

CONCLUSIONS: The gut microbiota-testis axis has emerged as a critical physiological pathway linking the microbiome to male reproductive function. This review provides an evidence-based framework for understanding this axis and highlights key knowledge gaps that must be addressed. Future research should integrate large-scale longitudinal cohorts, mechanistic exploration, and randomized controlled trials with fertility outcomes as primary endpoints to advance the field from descriptive correlations toward mechanism-driven clinical translation.},
}

@article {pmid42867288,
year = {2026},
author = {Kong, W and Zhang, H and Gui, J and Long, X and Chen, X and Ge, Y and Shao, W and Zhao, G and Cubero, FJ and Jiang, Z and Gu, A},
title = {Prophylactic oral diosgenin attenuates acute sleep deprivation-induced liver injury in mice via modulation of the gut microbiota and vascular barrier.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo01836j},
pmid = {42867288},
issn = {2042-650X},
abstract = {Acute sleep deprivation (SD) is an increasingly prevalent health risk, yet the early inflammatory processes associated with acute hepatic injury following SD remain largely elusive. Following a two-step screening of 265 natural products and bioactive small molecules, diosgenin (DG), a sapogenin found in Dioscorea species, was prioritized for subsequent in vivo evaluation. Under the rotating-platform paradigm in mice, 24-hour SD (SD24h) was associated with acute hepatic inflammation, increased overall intestinal permeability, gut vascular barrier (GVB)-associated alterations, gut microbiota dysbiosis, and elevated intestinal and hepatic lipopolysaccharide (LPS) levels. Prophylactic oral DG pretreatment attenuated hepatic and intestinal inflammatory responses, intestinal permeability changes, and GVB-associated alterations, while partially ameliorating SD-associated changes in the gut microbiota and intestinal and hepatic LPS levels. Fecal microbiota transplantation further showed that microbiota from SD24h donors transferred part of the hepato-intestinal inflammatory and barrier-associated phenotypes to antibiotic-pretreated recipients, whereas microbiota from DG-pretreated SD24h donors transferred an attenuated phenotype. Collectively, these findings support the involvement of the gut microbiota and intestinal barrier in acute SD-associated liver injury and indicate that prophylactic oral DG pretreatment attenuates these hepato-intestinal responses.},
}

@article {pmid42859560,
year = {2026},
author = {Dewan, A and Goulart, DB and Mascellino, MT},
title = {Gut microbiota dysbiosis: Pathogenic drivers and emerging phage-based therapeutics.},
journal = {AIMS microbiology},
volume = {12},
number = {3},
pages = {632-665},
pmid = {42859560},
issn = {2471-1888},
abstract = {Gut microbiota dysbiosis driven by pathogenic and opportunistic bacteria, including Clostridioides difficile, adherent-invasive Escherichia coli (AIEC), Salmonella enterica serovar Typhimurium, Fusobacterium nucleatum, Klebsiella pneumoniae, Enterococcus faecalis, and Campylobacter spp., disrupts colonization resistance, epithelial barrier integrity, and immune homeostasis, thereby contributing to the development of inflammatory and metabolic diseases. In this review, we summarize the mechanisms through which these microorganisms promote gut dysbiosis and critically evaluate current microbiome-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), live biotherapeutic products (LBPs), probiotics, and bacteriophage (phage) therapy. We review the preclinical and emerging clinical evidence supporting phage-based targeting of major dysbiosis-associated pathogens and examine the principal challenges limiting clinical translation, including phage resistance, immune-mediated clearance, safety considerations related to temperate phages, manufacturing and delivery constraints, and regulatory barriers. Although evidence remains predominantly preclinical, advances in phage engineering, artificial intelligence-guided phage selection, and systems-level microbiome modeling are expanding the potential of personalized phage therapeutics. Collectively, these developments position bacteriophage therapy as a promising addition to future microbiome-directed strategies for restoring gut microbial homeostasis and managing dysbiosis-associated disease.},
}

@article {pmid42860401,
year = {2026},
author = {Xu, Z and Jiang, H and Huang, W and Chan, A and Lin, Y and Chan, T and Lui, RN and Wong, MTL and Mak, JWY and Chan, FKL and Chevarin, C and Colombel, JF and Buisson, A and Ng, SC},
title = {Fecal microbiota transplantation for the decolonization of mucosal adherent-invasive Escherichia coli in Crohn's disease: an open-label pilot study.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42860401},
issn = {2041-1723},
mesh = {Humans ; *Crohn Disease/therapy/microbiology ; Pilot Projects ; *Fecal Microbiota Transplantation/methods/adverse effects ; Female ; *Escherichia coli/genetics/physiology ; Male ; Feces/microbiology ; Adult ; *Intestinal Mucosa/microbiology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; *Escherichia coli Infections/therapy/microbiology ; Young Adult ; Gastrointestinal Microbiome ; Treatment Outcome ; },
abstract = {Adherent-invasive Escherichia coli (AIEC) is implicated in Crohn's disease (CD) pathogenesis, but whether fecal microbiota transplantation (FMT) clears mucosal AIEC and alters fecal and mucosal microbiomes has not been studied. In this open-label pilot study, thirty adults with CD and seropositivity for serum anti-E.coli antibody (AEcAb) received a single colonoscopic FMT from one of two donors (ClinicalTrials.gov identifier NCT05611866). The primary outcome was adverse events (AEs) within 12 weeks after FMT; secondary outcomes included changes in mucosal AIEC, clinical measures, and fecal and mucosal microbiome profiles. Shotgun metagenomic sequencing for fecal samples and 16S rRNA sequencing for ileal mucosal samples were performed at baseline and after FMT. Baseline AEcAb levels were higher in patients with mucosal AIEC colonization (p = 0.019) and remained elevated after FMT. No FMT-related serious adverse events were reported. FMT was associated with mucosal AIEC decolonization in all 8 evaluable baseline-positive patients. Mucosal alpha diversity increased after FMT (p = 0.023), which correlated with reduced fecal calprotectin (p = 0.034). Microbial pathway profiles in CD patients resembled those of their respective donors with reduced donor-recipient dissimilarity post-FMT (p = 0.030), particularly among recipients with mucosal AIEC decolonization (p = 0.039). In conclusion, this open-label pilot study demonstrates the feasibility of FMT for modulating mucosal AIEC colonization in CD and highlights the importance of capturing microbial changes at the disease site that may be undetectable in fecal samples.},
}

Humans
*Crohn Disease/therapy/microbiology
Pilot Projects
*Fecal Microbiota Transplantation/methods/adverse effects
Female
*Escherichia coli/genetics/physiology
Male
Feces/microbiology
Adult
*Intestinal Mucosa/microbiology
Middle Aged
RNA, Ribosomal, 16S/genetics
*Escherichia coli Infections/therapy/microbiology
Young Adult
Gastrointestinal Microbiome
Treatment Outcome

@article {pmid42860646,
year = {2026},
author = {Tai, YC and Lin, CH},
title = {Targeting the Gut to Modify Parkinson's Disease: From Mechanisms to Potential Therapeutics.},
journal = {Journal of movement disorders},
volume = {},
number = {},
pages = {},
doi = {10.14802/jmd.26285},
pmid = {42860646},
issn = {2005-940X},
abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disorder and its prevalence continues to rise with population aging. Its cardinal motor features arise from the loss of dopaminergic neurons in the substantia nigra, accompanied by intraneuronal α-synuclein aggregates known as Lewy bodies. Neuropathological evidence suggests that, in a subset of patients, α-synuclein pathology first appears in the enteric nervous system and ascends to the brain via the gut-brain axis. Consistent with this "body-first" trajectory, a growing body of work has documented distinct alterations in gut microbial composition and microbiota-derived metabolites in people with PD relative to healthy individuals, with some changes detectable in the prodromal phase. Current management, whether dopaminergic pharmacotherapy or deep brain stimulation, alleviates motor symptoms but does not slow neurodegeneration, and long-term treatment is complicated by motor fluctuations and other adverse effects. Therapies directed at the underlying disease process are therefore urgently needed. Because early perturbations of the gut microenvironment appear to contribute to PD pathogenesis, interventions that restore gut homeostasis represent a rational disease-modifying strategy, particularly for patients whose pathology originates in the gut. This review synthesizes current understanding of how the gut microbiota shapes the gut-brain axis in PD, spanning immune, metabolic, neuroendocrine, and neural pathways, and critically appraises the emerging evidence for microbiota-directed interventions, including fecal microbiota transplantation, probiotics, and prebiotics, as candidate disease-modifying therapies.},
}

@article {pmid42861589,
year = {2026},
author = {Xie, YZ and Sun, CX and Fu, TT and Jin, Z and Nalinratana, N and Rojsitthisak, P and Zhao, K and Hua, JS and Pei, FY and Wang, XH},
title = {Nanoformulated Curcumin Ameliorates Ulcerative Colitis via Gut Microbiota Modulation and Barrier Function Restoration.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-26},
doi = {10.1142/S0192415X26500837},
pmid = {42861589},
issn = {1793-6853},
abstract = {The gut microbiota is increasingly recognized as a key mediator of the anticolitis effects of curcumin (CUR). However, the clinical translation of this promising activity is severely hampered by CUR's low solubility and poor bioavailability. Although nanoencapsulation represents a promising strategy to address these limitations, the preventive effect of nanocurcumin (nano-CUR) against colitis remains largely unexplored. The present study aimed to elucidate the preventive effects of nano-CUR on intestinal barrier function, gut microbiota composition, and metabolic profiles in a murine model of dextran sulfate sodium (DSS)-induced colitis. The results demonstrated that pre-supplementation of nano-CUR significantly ameliorated disease severity, attenuated intestinal barrier disruption, and suppressed colonic inflammation in mice with DSS-induced colitis. Mechanistically, integrated 16S rRNA sequencing and untargeted metabolomics demonstrated that nano-CUR-restored microbial homeostasis and enhanced the production of short-chain fatty acids, linking microbial shifts to anti-inflammatory outcomes. Fecal microbiota transplantation (FMT) further validated the causal role of the nano-CUR-remodeled microbiota in conferring protection. Collectively, these findings decipher the mechanism by which nano-CUR interacts with the gut microbiota, confirming that dietary nano-CUR consumption protects against ulcerative colitis by modulating the gut microbiome and its metabolic output.},
}

@article {pmid42861819,
year = {2026},
author = {Zhao, W and Yan, D},
title = {Supplementation with Akkermansia muciniphila Enhances the αPD-1 Efficacy in Mice Transplanted with Gut Microbiota from Patients with Colorectal Cancer.},
journal = {Current cancer drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680096507014261001062033},
pmid = {42861819},
issn = {1873-5576},
abstract = {INTRODUCTION: The resistance of colorectal cancer (CRC) to PD-1 blockade has positioned it as a critical focus of global research efforts. The gut microbiota is a key regulator of anti-tumor immunity, but research on bacteria that are clearly associated with primary resistance to PD-1 blockade in colorectal cancer remains incomplete.

METHODS: In this study, C57BL/6 mice were subjected to antibiotic pretreatment to deplete endogenous gut microbiota. The mice were then gavaged with fecal suspensions from treatment-naïve CRC patients or healthy donors, subsequently implanted with MC38 tumor cells to establish the tumor model, and then treated with the drug. Gut microbial composition was analyzed by 16S rRNA sequencing, while tumor-infiltrating immune cells and cytokine profiles were characterized using flow cytometry and immunohistochemistry, respectively.

RESULTS: CRC patient microbiota conferred resistance to anti-PD-1 therapy in mice, an effect completely reversed by oral Akkermansia muciniphila (Akk). Mechanistically, Akk reconfigured the tumor immune microenvironment, leading to a substantial increase in CD8+ T cell infiltration and function. Crucially, this potent local anti-tumor immunity was achieved without systemic immune activation.

DISCUSSION: In summary, this study establishes that Akk amplifies the local CD8⁺ T cell response, sensitizing tumors to anti-PD-1 therapy, without inducing a systemic inflammatory response.

CONCLUSION: These findings position Akk supplementation as a promising, targeted strategy to overcome PD-1 immunotherapy resistance of MSS-CRC with a favorable safety profile.},
}

@article {pmid42852084,
year = {2026},
author = {Fan, Y and Du, L and Luo, Q and Mei, T and Zhou, A and Liu, H and Khan, MQ and Gao, F and Dong, J},
title = {The lung-gut-brain axis in non-small-cell lung cancer: a narrative review with a systematic search of three signaling pathways.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1932225},
pmid = {42852084},
issn = {1664-3224},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/metabolism/immunology/microbiology/therapy ; *Lung Neoplasms/metabolism/immunology/microbiology/therapy ; *Signal Transduction ; Animals ; *Gastrointestinal Microbiome ; *Brain/metabolism ; *Lung/metabolism/immunology ; },
abstract = {BACKGROUND: The gut-lung axis, the long-range communication between the intestinal microbiota and the lungs, has been shown to influence immunotherapy responses in non-small-cell lung cancer (NSCLC). Existing reviews, however, focus almost exclusively on the chemical signaling dimension of microbial metabolites. The relay function of enteroendocrine hormones and the integrative role of the nervous system have yet to be incorporated into a unified framework.

METHODS: We searched seven databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP) from inception to June 2026 for original studies and reviews addressing gut microbiota and lung-gut-brain axis mechanisms in the context of NSCLC or small-cell lung cancer. Two authors independently performed study selection, data extraction, and thematic classification. A narrative synthesis was conducted, with evidence organized along three signaling axes: soluble metabolites, the metabolic-endocrine axis, and neuroimmune integration. As a narrative review with a systematic search, this study was registered on PROSPERO (CRD420261425826), while formal risk-of-bias assessment and GRADE evaluation were not performed.

RESULTS: A total of 168 studies was included (only a subset of these included studies cited in the main text). The volume of evidence across the three axes formed a pronounced gradient. Soluble metabolites (short-chain fatty acids, tryptophan metabolites, and bile acids) have been cross-validated in clinical cohorts, animal models, and in vitro experiments; fecal microbiota transplantation and prebiotic strategies have entered clinical trials. The metabolic-endocrine axis rests on a solid foundation in normal physiology, but the key bridging nodes in the NSCLC disease context remain untested. Evidence for the neuroimmune integration axis is the sparsest: the only support for a direct transport function of the vagus nerve comes from a non-peer-reviewed preprint in a non-cancer model, and the full neuroendocrine signal transduction chain remains hypothetical. To address this gap, we outline a pathway model annotated with evidence levels at each node.

CONCLUSIONS: Research on the lung-gut-brain axis is heavily concentrated in the chemical dimension. The mechanistic gaps in the endocrine and neural dimensions represent the principal barrier for the field's transition from correlational description to causal mechanism studies.},
}

Humans
*Carcinoma, Non-Small-Cell Lung/metabolism/immunology/microbiology/therapy
*Lung Neoplasms/metabolism/immunology/microbiology/therapy
*Signal Transduction
Animals
*Gastrointestinal Microbiome
*Brain/metabolism
*Lung/metabolism/immunology

@article {pmid42856694,
year = {2026},
author = {Soveral, LF and Holanda, LRL and Assunção, IBF and Gomes, LG and de Souza, IB and Rodrigues, GS and Vanny, PA and Bruna-Romero, O and Palmeiro, JK and Scheffer, MC and Sincero, TCM and Zárate-Bladés, CR},
title = {Identification of antibiotic resistance genes in fecal microbiota selected donors during the establishment of a biobank in the south of Brazil.},
journal = {Frontiers in antibiotics},
volume = {5},
number = {},
pages = {1905540},
pmid = {42856694},
issn = {2813-2467},
abstract = {Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is increasingly explored for other dysbiosis-related disorders. However, its implementation as a regulated therapeutic strategy requires robust donor screening, biosafety frameworks, and standardized processing workflows. Here, we describe the establishment of the first fecal microbiota biobank in southern Brazil and evaluate the incorporation of metagenomic sequencing as a complementary layer of donor characterization and safety assessment. A structured donor selection pipeline based on international guidelines was implemented, integrating clinical screening, biochemical and serological testing, and microbiological analyses. Of 100 screened candidates, only four donors met all eligibility criteria and were included in the biobank, highlighting the stringency of the selection process. Shotgun metagenomic sequencing revealed a diverse resistome across all donors, including a shared core set of resistance genes alongside marked interindividual variability. Dominant resistance determinants included tetracycline-associated genes, ermF, CfxA-type β-lactamases, and aminoglycoside-modifying enzymes, which were associated with specific gut taxa. Genomic context analysis further identified four ARG-containing contigs with features compatible with potential mobility, although active horizontal gene transfer was beyond the scope of this study. Notably, tet(Q) and ermF were predominantly associated with Bacteroides fragilis, supporting its role as a reservoir of resistance determinants in the gut microbiota. These findings support the use of metagenomic profiling as a complementary approach to donor characterization and risk assessment rather than as a standalone criterion for donor exclusion. Overall, this study provides a framework for microbiota biobank implementation and highlights the potential of metagenomic analysis to complement conventional biosafety screening in FMT.},
}

@article {pmid42856976,
year = {2026},
author = {Sharma, S and Pachauri, A and Nagar, H and Thakkar, V and Patel, K},
title = {Targeting gut dysbiosis: a new frontier in MASLD management.},
journal = {Frontiers in systems biology},
volume = {6},
number = {},
pages = {1937809},
pmid = {42856976},
issn = {2674-0702},
abstract = {Globally, Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prominent leading cause of CLD, which is intricately linked with obesity, T2D, and metabolic syndrome. Recent insights in pathophysiologically of MASLD have shifted from the traditional "two-hit" model to a "multiple-hit" paradigm, demonstrating the importance of understanding the gut-liver axis and gut dysbiosis as central drivers of disease progression. Hence, this narrative review explores the mechanistic pathways through which an altered gut microbiome contributes to MASLD, by specifically emphasizing intestinal barrier disruption, endotoxemia, altered bile acid metabolism, and SCFA imbalance. These dysregulations trigger oxidative stress, leading to systemic inflammation and insulin resistance, propelling simple steatosis toward steatohepatitis and fibrosis at last. Furthermore, we also highlighted the diagnostic utility of microbial signatures and multi-omics approaches in identifying disease-specific microbial shifts, such as the depletion of beneficial SCFA-producing bacteria like Faecalibacterium and Akkermansia. Eventually, to address the growing hepatic-associated health burden, microbiome-targeted therapeutics can emerge as one of the promising contributors. In this review, we synthesise and demonstrate the current and prospective interventions, including dietary modifications, biotics (probiotics, prebiotics, synbiotics), and FMT. Additionally, we also show the transition of care toward precision microbiome therapies utilizing engineered bacteria, bacteriophages, and AI-guided patient stratification. While current microbiome-centric treatments demonstrate promise in modulating hepatic inflammation and restoring mucosal integrity, their clinical translation remains hindered by patient heterogeneity and a lack of standardized protocols. Ultimately, managing MASLD effectively will require moving beyond broad ecosystem resets toward highly tailored, multi-omics-driven precision medicine to accurately target individualized microbial deficits.},
}

@article {pmid42857238,
year = {2026},
author = {Ma, J and Hou, Z},
title = {Gut Microbiota-Immune-Inflammation Axis as a Putative Pathogenic Axis in Chronic Insomnia: Mechanistic Dissection of NLRP3 Inflammasome and NF-κB Signaling.},
journal = {International journal of general medicine},
volume = {19},
number = {},
pages = {645057},
pmid = {42857238},
issn = {1178-7074},
abstract = {Chronic insomnia represents one of the most prevalent sleep disorders worldwide, yet current symptomatic treatments largely fail to target its root pathophysiology. Moving beyond conventional neurocentric frameworks, converging evidence positions gut microbiota dysbiosis as a potential upstream contributor to insomnia via the microbiota-gut-brain axis, with immune-inflammatory cascades serving as proposed mediating pathway. Mechanistically, disrupted gut microbial communities compromise intestinal mucosal barrier integrity, enabling lipopolysaccharide translocation that activates TLR4-mediated NF-κB signaling. This triggers systemic low-grade inflammation, marked by elevated pro-inflammatory cytokines IL-1β, IL-6, IL-17 and TNF-α, reduced anti-inflammatory IL-4 and IL-10, and Th17/Treg immune imbalance. Centrally, circulating inflammatory signals activate the NLRP3 inflammasome, driving caspase‑1‑dependent pyroptosis and a pro‑inflammatory microglial activation state (conventionally described as "M1‑like" polarization), which disrupts sleep-wake neural circuitry and hypothalamic-pituitary-adrenal axis homeostasis. Dysregulated PI3K/Akt signaling and aberrant microbial metabolites-including depleted short-chain fatty acids and a pathological shift in tryptophan metabolism toward the neurotoxic kynurenine pathway-further amplify the vicious cycle between sleep disturbance and neuroinflammation. This review systematically maps the full pathological cascade from intestinal dysbiosis to central insomnia phenotypes, and compares translational strategies including psychobiotic strains, fecal microbiota transplantation, dietary intervention and traditional Chinese medicine formulas targeting this axis. Collectively, this work proposes an integrated microbiota-immune-sleep regulatory framework, offering novel mechanistic insights and microbiome-based therapeutic avenues for precision insomnia management.},
}

@article {pmid42858836,
year = {2026},
author = {Mujagić, Z and Keszthelyi, D},
title = {Successful Engraftment Without Relief: Closing the Chapter on Fecal Microbiota Transplantation in IBS?.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2026.10.001},
pmid = {42858836},
issn = {1528-0012},
}

@article {pmid42859348,
year = {2026},
author = {Lin, W and Shu, Z and Liu, G and Fang, J and Ding, S},
title = {The Gut-Brain Axis and Neurodegenerative Diseases: From Mechanistic Pathways to Therapeutic Interventions.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {42859348},
issn = {1867-1314},
support = {2024RC2053//Yuelushan Laboratory joint talent introduction project/ ; Grant No. kq2502176//Natural Science Foundation of Changsha, China/ ; 24B0219//Scientific Research Project of Hunan Provincial Department of Education/ ; 2025JGZD053//Hunan Province Postgraduate Education Teaching Reform Research Project/ ; 2023YFD1301200//National Key Research and Development Program of China/ ; HARS-06//Hunan Poultry Industry Technology System/ ; },
abstract = {As the global population ages, the incidence of neurodegenerative diseases (NDDs) has increased. Neurodegenerative diseases have complex pathogenesis and currently lack fundamental treatment methods. The gut-brain axis (GBA) participates in the pathogenesis of NDDs through bidirectional communication between the gut microbiota and the central nervous system (CNS). This review systematically introduces the pathogenic characteristics of representative NDDs such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), as well as the association mechanisms between these diseases and GBA. The pathogenic characteristics of NDDs are closely related to changes in the composition of the gut microbiota and differences in gut microbiota metabolites (such as short-chain fatty acids (SCFAs), neurotransmitters, tryptophan metabolites, etc.). These changes influence the CNS through multiple pathways, including neuroendocrine, vagus nerve, and immune regulation, ultimately contributing to the onset and progression of the diseases. Furthermore, we have collected and summarized preclinical and clinical evidence from recent years regarding therapeutic interventions based on the GBA mechanism, including probiotics, prebiotics, and fecal microbiota transplantation (FMT). Nevertheless, major knowledge gaps remain, particularly regarding causality between gut microbiota changes and NDDs, the underlying molecular mechanisms, and the clinical efficacy of GBA-targeted therapies. This article aims to review the mechanisms of the interaction between the gut microbiota and the brain in neurodegenerative diseases, and based on the existing experimental evidence, provide theoretical basis and future development directions for future prevention and treatment strategies targeting GBA.},
}

@article {pmid42849638,
year = {2026},
author = {Shareef, Z and Hussain, HI and Aqib, AI and Malik, MSU and Rehman, SU},
title = {Combating Antimicrobial Resistance: Emerging Non-Traditional Therapeutics, Clinical Translation Challenges, and Future Perspectives.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108871},
doi = {10.1016/j.micpath.2026.108871},
pmid = {42849638},
issn = {1096-1208},
abstract = {Antimicrobial resistance (AMR) has emerged as one of the most severe global health threats. The rapid expansion of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens compromises the effectiveness of conventional antibiotics. Globally, ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) have led to therapeutic failure, prolonged hospitalization, and increased mortality rates. This review identifies the molecular mechanisms, including enzymatic antibiotic inactivation, efflux pump overexpression, biofilm formation, and horizontal gene transfer, that underline the resistance of disseminated pathogens to antibiotics in clinical, agricultural, and environmental settings. Antibiotic overuse and pharmaceutical and agricultural discharges create persistent reservoirs for the dissemination of AMR genes. Furthermore, we evaluated the non-traditional antibacterial efficacy of antimicrobial peptides, bacteriophage therapy, monoclonal antibodies, probiotics, fecal microbiota transplantation, anti-virulence agents, CRISPR-Cas precision antimicrobials, and nanotechnology-based drug delivery platforms. Current preclinical and clinical evidence indicates the eradication of resistant pathogens, disruption of biofilms, and preservation of host microbiota, thereby reducing the selective pressure associated with broad-spectrum antibiotics. Despite these advances, major translational barriers, such as pharmacokinetic instability, manufacturing limitations, and insufficient clinical validation, restrict the implementation of the framework. In the future, the AMR management framework will require precision medicine, artificial intelligence, and One Health-based integration via multidisciplinary collaboration.},
}

@article {pmid42851075,
year = {2026},
author = {Liu, Y and Qian, H and Wu, C and Wang, A and Lu, S and Sun, Y and Du, D and Lei, Y and Shen, X},
title = {Dietary aqueous extract of Astragalus sinicus alleviates obesity by reshaping gut microbiota and metabolism.},
journal = {Journal of the science of food and agriculture},
volume = {},
number = {},
pages = {},
doi = {10.1002/jsfa.71149},
pmid = {42851075},
issn = {1097-0010},
support = {2022AH050199//Educational Commission of Anhui Province of China/ ; (SKKF20260102,start-upfundstoXS)//Funds from the Anhui Normal University/ ; 2208085MH209//Anhui Provincial Natural Science Foundation/ ; 2022AH010012//the Outstanding Innovative Research Team for Molecular Enzymology and Detection in Anhui Provincial Universities/ ; 2022AH030022//the Fund for Excellent Young Scholars in Higher Education of Anhui Province of China/ ; },
abstract = {BACKGROUND: Obesity induced by long-term high-fat diet (HFD) consumption is closely associated with metabolic disorders and gut microbiota dysbiosis. Although plant-derived extracts show anti-obesity potential, microbiota-dependent mechanisms and causal relevance remain incompletely understood. Astragalus sinicus L. is a traditional medicinal and dietary plant, yet the metabolic effects of its aqueous extract have not been systematically evaluated. This study investigated the anti-obesity effects of an aqueous extract of Astragalus sinicus (ASAE) and determined whether gut microbiota remodeling mediates its metabolic benefits. HFD-induced obese mice were treated with ASAE and subjected to comprehensive metabolic phenotyping. The chemical composition of ASAE was characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Gut microbiota composition, fecal metabolomic profiles, and adipose tissue transcriptomes were analyzed using 16S rRNA gene sequencing, untargeted metabolomics, and RNA sequencing, respectively. Fecal microbiota transplantation was performed to assess microbiota-dependent causality.

RESULTS: ASAE significantly improved glucose tolerance, insulin sensitivity, dyslipidemia, and hepatic steatosis in HFD-fed mice without affecting food intake. ASAE markedly reshaped gut microbiota structure and fecal metabolomic profiles, particularly regulating steroid- and lipid-related metabolites. Adipose transcriptomic analysis revealed that ASAE reversed HFD-induced transcriptional programs associated with immune activation and lipid metabolic dysfunction. Importantly, transplantation of microbiota from ASAE-treated donors recapitulated these metabolic improvements in obese recipient mice, demonstrating a microbiota-dependent effect.

CONCLUSION: ASAE alleviates HFD-induced obesity through gut microbiota-mediated mechanisms, providing causal evidence linking microbial remodeling to host metabolic improvement. These findings highlight ASAE as a promising microbiota-targeted intervention for obesity. © 2026 Society of Chemical Industry.},
}

@article {pmid42851358,
year = {2026},
author = {Liu, R and Liu, Y and Jiang, J and Yang, Z},
title = {Quantitative mapping of gut microbiota feature importance to TCM syndrome elements in clinical T2DM stages.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1910757},
pmid = {42851358},
issn = {2235-2988},
mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/diagnosis ; *Medicine, Chinese Traditional ; *Gastrointestinal Microbiome/genetics ; Female ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Syndrome ; Support Vector Machine ; Bacteria/classification/genetics/isolation & purification ; Aged ; },
abstract = {INTRODUCTION: The clinical phenotype of modern type 2 diabetes mellitus (T2DM) has diverged from the classical traditional Chinese medicine (TCM) syndrome of Xiao Ke (wasting-thirst), with obesity replacing emaciation as the dominant presentation and challenging traditional symptom-based syndrome differentiation. The TCM syndrome element system, a quantifiable framework inherently compatible with molecular-level parameters, positions the gut microbiota - causally linked to T2DM, stage-specific in composition, and amenable to targeted intervention - as an ideal molecular anchor for refining syndrome differentiation. However, the quantitative feature importance of specific gut microbes for individual syndrome elements remains undetermined.

METHODS: We enrolled 154 participants across three T2DM stages (51 pre-diabetes, 53 T2DM, 50 T2DM with complications) for 16S rDNA sequencing, syndrome element assessment, and machine learning.

RESULTS: Mendelian randomization identified 21 gut microbiota taxa and functional pathways causally implicated in T2DM in East Asian populations, providing biological priors for subsequent analyses. Support vector machine (SVM) models with SHAP values quantified microbial feature importance for individual syndrome elements, revealing progressive evolution from dampness, qi deficiency, and spleen (pre-diabetes) to dampness, phlegm, heat, and kidney (complications). Bacteroides and Faecalibacterium showed the highest feature importance for spleen (4.9% each), Veillonella showed the highest feature importance for dampness (3.4%), and Bifidobacterium was the top feature for phlegm (1.0%). Fecal microbiota transplantation (FMT) in 34 patients provided interventional evidence consistent with the model: 26.7% of post-FMT differentially abundant genera (4 of 15) and 7.5% of differentially abundant species (8 of 106) overlapped with top-ranking SVM features.

DISCUSSION: This proof-of-concept study provides the first quantitative mapping of gut microbiota feature importance to TCM syndrome elements, establishing an integrated framework combining MR-based causal prioritization, ML-based feature importance mapping, and FMT-based intervention validation for micro-syndrome differentiation.},
}

Humans
*Diabetes Mellitus, Type 2/microbiology/diagnosis
*Medicine, Chinese Traditional
*Gastrointestinal Microbiome/genetics
Female
Male
Middle Aged
RNA, Ribosomal, 16S/genetics
Syndrome
Support Vector Machine
Bacteria/classification/genetics/isolation & purification
Aged

@article {pmid42851568,
year = {2026},
author = {Enwere, M and Bryan, NS and Onu, A and Neufeld, M and El-Hussein, MT and Yakub, I and Omale, C and Onyedike, O and Atim, T and Agbeyomi, O and Davies, E and Okeke, UE and Holmes, L},
title = {The microbiome-nitric oxide axis in cancer immunotherapy: a targeted qualitative systematic review of mechanistic and translational evidence.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1904698},
pmid = {42851568},
issn = {1664-3224},
mesh = {Humans ; *Neoplasms/therapy/immunology/metabolism/microbiology ; *Nitric Oxide/metabolism/immunology ; Animals ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Fecal Microbiota Transplantation ; Translational Research, Biomedical ; },
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but responses vary substantially among patients. Clinical studies have associated features of the gut microbiome with ICI outcomes, while experimental evidence suggests that microbial metabolites and nitric oxide (NO)-related pathways may influence antitumor immunity and tumor vascular biology. This qualitative systematic review evaluated the evidence supporting a proposed microbiome-NO-ICI framework.

METHODS: Five databases were searched for peer-reviewed studies published between January 2000 and August 2025. Fifty-four distinct primary studies met the eligibility criteria, comprising 21 clinical studies, 19 animal studies and 14 in vitro mechanistic studies. Evidence was synthesized narratively according to study type and thematic domain.

RESULTS: Several clinical cohorts associated enrichment of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bifidobacterium species and other short-chain fatty acid-producing taxa with favorable ICI outcomes; however, the reported microbial signatures varied across cohorts and analytical platforms. Microbial-transfer experiments and early non-randomized fecal microbiota transplantation studies provide proof-of-concept evidence that microbiome composition can influence antitumor immune responses, although the clinical intervention evidence remains preliminary. Animal and cellular studies indicate that microbial metabolites, host nitric oxide synthase pathways and reactive nitrogen signaling can affect immune-cell function, vascular regulation and tumor hypoxia. Direct clinical evidence linking microbiota-mediated nitrate reduction or dietary nitrate supplementation to improved ICI outcomes is lacking. Human dietary nitrate studies conducted outside oncology demonstrate increased circulating nitrate and nitrite and measurable vascular effects but do not establish anticancer or ICI efficacy.

CONCLUSION: The microbiome-NO-ICI axis should be regarded as a testable integrative model linking microbial ecology, immune regulation and tumor vascular biology. Current evidence supports biological plausibility but is insufficient to establish NO- or microbiome-directed interventions as effective adjuncts to ICI therapy. Prospective mechanistic studies and biomarker-driven clinical trials are required before therapeutic translation.},
}

Humans
*Neoplasms/therapy/immunology/metabolism/microbiology
*Nitric Oxide/metabolism/immunology
Animals
*Gastrointestinal Microbiome/immunology
*Immunotherapy/methods
*Immune Checkpoint Inhibitors/therapeutic use
Fecal Microbiota Transplantation
Translational Research, Biomedical

@article {pmid42851677,
year = {2026},
author = {Plaza-Diaz, J and Voidarou, CC and Bezirtzoglou, E and Stavropoulou, E},
title = {Editorial: Rodent model organisms: therapeutic treatments and drugs interaction with the gut microbiome, volume II.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1962495},
doi = {10.3389/fmicb.2026.1962495},
pmid = {42851677},
issn = {1664-302X},
}

@article {pmid42843354,
year = {2026},
author = {Hasanuzzaman, M and Bang, CS and Lee, JJ and Gong, EJ},
title = {Fecal Microbiota Transplantation Beyond Clostridioides difficile Infection: Expanding Indications, Mechanisms, and Future Directions.},
journal = {Journal of Korean medical science},
volume = {41},
number = {38},
pages = {e335},
pmid = {42843354},
issn = {1598-6357},
support = {RS-2023-00223501/NRF/National Research Foundation of Korea/Korea ; /Hallym/Hallym University/Korea ; },
mesh = {*Fecal Microbiota Transplantation ; Humans ; *Clostridium Infections/therapy/microbiology ; Inflammatory Bowel Diseases/therapy ; Clostridioides difficile ; Irritable Bowel Syndrome/therapy ; Dysbiosis/therapy ; Gastrointestinal Microbiome ; Nervous System Diseases/therapy ; Metabolic Diseases/therapy ; Animals ; },
abstract = {Fecal microbiota transplantation (FMT) has emerged as a transformative therapeutic approach to restore gut microbial homeostasis. The most established indication is recurrent Clostridioides difficile infection (CDI), demonstrating that restoring ecosystem-level microbiota has substantial clinical benefits. Building on this success, FMT is now being investigated across a broader range of indications associated with gut dysbiosis and altered microbiome-host signaling, including inflammatory bowel disease, irritable bowel syndrome, metabolic, and neurological disorders. Mechanistic insights into the gut-organ axes provide biological plausibility for this expansion; gut dysbiosis can function as a modifiable upstream driver of host metabolism, immune-neural signaling, and barrier function. However, the clinical benefits beyond CDI remain heterogeneous and often modest, highlighting the need for further research on patient stratification, standardized protocols, and mechanistic biomarkers. Furthermore, regulatory frameworks remain heterogeneous worldwide, and recent approvals of standardized microbiota-based products for recurrent CDI represent a transition toward treating microbiome therapeutics as regulated biologics. This review synthesizes the mechanistic rationale and current evidence for FMT beyond CDI and outlines future directions for personalized and next-generation microbiome therapeutics.},
}

*Fecal Microbiota Transplantation
Humans
*Clostridium Infections/therapy/microbiology
Inflammatory Bowel Diseases/therapy
Clostridioides difficile
Irritable Bowel Syndrome/therapy
Dysbiosis/therapy
Gastrointestinal Microbiome
Nervous System Diseases/therapy
Metabolic Diseases/therapy
Animals

@article {pmid42844513,
year = {2026},
author = {Shruti, and Bala, K},
title = {The Gut-Insulin Axis in Polycystic Ovary Syndrome: A Narrative Review of Gut Dysbiosis, Inflammation, and Emerging Therapeutic Strategies.},
journal = {Reproductive sciences (Thousand Oaks, Calif.)},
volume = {},
number = {},
pages = {},
pmid = {42844513},
issn = {1933-7205},
abstract = {Polycystic ovary syndrome (PCOS) is a complicated, endocrine-endemic disorder with a prevalence rate of 8-13% in reproductive-age women in the world, which manifests through insulin resistance, hyperandrogenism, and reproductive dysfunction. Despite its high global prevalence, existing therapeutic interventions focus predominantly on symptom management rather than targeting the heterogeneous and multifactorial pathophysiology of the syndrome. Intestinal barrier integrity is destroyed by dysbiosis of the gut microbiota and induces endotoxemia and chronic low-grade inflammation through signalling pathways, such as LPS-TLR4-NF-kB signalling, which contribute to increased insulin resistance and androgen excess. These mechanistic pathways we dissect include changes in short-chain fatty acids (SCFAs), bile acid metabolism, involvement of FXR and TGR5 receptors, neuroendocrine regulation of the gut-brain axis, and microbial metabolites (tryptophan and agmatine), which altogether alter metabolic and reproductive abnormalities in PCOS. The preclinical evidence in the area of fecal microbiota transplantation proves the causal component of microbiota imbalance in the phenotype of PCOS. Dietary interventions that have been reviewed are fiber and resistant starch modulation, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and pharmacotherapies like metformin, which also alter the microbiome. They are heading towards individualized microbiome-based therapies and diagnostics, aided by artificial intelligence and standardized biomarkers. This review explains the emerging role of the gut-insulin axis as an important factor in the pathogenesis of PCOS and uses a novel way of combining them as a radical intervention for personalized and innovative PCOS treatment, which has the potential to enhance metabolic and endocrine health, as well as reproductive outcomes.},
}

@article {pmid42844664,
year = {2026},
author = {Liu, M and Luo, M and Huang, Y and Ji, T and Wang, Y and Wang, Q and Huang, J and Jiang, T and Zhang, C and Mi, T and Cheng, M},
title = {Time-Restricted Feeding Delays Cardiovascular Aging by Increasing Acetic Acid Through Remodeling Gut Microbiota.},
journal = {Aging cell},
volume = {25},
number = {10},
pages = {e70728},
pmid = {42844664},
issn = {1474-9726},
support = {2024ZD0539100//the Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 82371599//the National Natural Science Foundation of China/ ; 82070241//the National Natural Science Foundation of China/ ; 2025AFB207//the Natural Science Foundation of Hubei Province/ ; U24A20741//the National Natural Science Foundation Regional Innovation and Development Joint Fund/ ; 202405AF140057//Zhang Cuntai Expert Workstation of Yunnan Province/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Acetic Acid/metabolism ; Intermittent Fasting ; *Aging ; Male ; Mice, Inbred C57BL ; },
abstract = {Time-restricted feeding (TRF) restricts food intake to daily windows, yet its efficacy against vascular aging and underlying mechanisms remain unclear. Here, we demonstrate that TRF attenuates angiotension II -induced accelerated vascular aging by reshaping gut microbiota, stabilizing microbial diversity, and elevating the Firmicutes/Bacteroidetes ratio. TRF preserved intestinal barrier integrity, upregulated tight junction proteins (Occludin, ZO-1, MUC2), reduced serum lipopolysaccharide, and suppressed systemic inflammation. These benefits translated into alleviated hypertension, aortic stiffness (reflected by pulse wave velocity), and pathological cardiac remodeling. Fecal microbiota transplantation recapitulated these effects, whereas antibiotic-induced microbiota depletion abolished TRF protection; importantly, exogenous acetate supplementation fully restored the phenotypes, establishing acetic acid as the critical downstream mediator. Mechanistically, acetic acid bound to GPR43, inhibited HDAC3, increased H4K8ac acetylation, blocked NLRP3-mediated pyroptosis, and reduced senescence markers (p53, p21, p16) in human umbilical vein endothelial cells, aorta, and heart. 16S rRNA sequencing and short - chain fatty acids metabolomic profiling further identified Limosilactobacillus as the primary acetic acid-producing bacterium enriched by TRF. Together, we uncover a Limosilactobacillus-acetic acid-GPR43/HDAC3/H4K8ac/NLRP3 axis, offering mechanistic insights into TRF as a non-pharmacological strategy against age-related cardiovascular diseases.},
}

Animals
*Gastrointestinal Microbiome
Humans
*Acetic Acid/metabolism
Intermittent Fasting
*Aging
Male
Mice, Inbred C57BL

@article {pmid42845110,
year = {2026},
author = {Scheperjans, F and Borghammer, P and Pfeiffer, RF and Appel-Cresswell, S and Keshavarzian, A},
title = {The Gut-Brain Axis in Parkinson's Disease: From Clinical Observation toward Mechanism-Based Precision Medicine.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/mds.70566},
pmid = {42845110},
issn = {1531-8257},
support = {//Sigrid Juséliuksen Säätiö/ ; 1U01DK140923-01/NH/NIH HHS/United States ; //Pacific Parkinson's Research Institute/ ; },
abstract = {Gastrointestinal dysfunction is increasingly recognized as a core feature of Parkinson's disease (PD), affecting quality of life, nutrition, medication response, and potentially the earliest stages of pathogenesis. This perspective traces the evolution of the gut from a neglected source of non-motor symptoms to a central component of biological models of PD. Gastrointestinal manifestations are physiologically heterogeneous and require objective phenotyping to distinguish dysphagia, gastroparesis, slow transit, defecatory dysfunction, and overlapping mechanisms. The body-first/brain-first framework further suggests that Lewy pathology may follow distinct anatomical trajectories, with early enteric and autonomic involvement defining a subgroup in which gut-directed biomarkers and therapies may be especially relevant. Alterations of the gut microbiome are reproducibly associated with PD, although geography, constipation, medication, diet, disease stage, and reverse causation complicate interpretation. Emerging work is shifting from taxonomy toward microbial functions and host pathways, including barrier integrity, immune and enteroendocrine signaling, short-chain fatty acids, glucagon-like peptide-1 (GLP-1), host genetic susceptibility, α-synuclein aggregation and propagation, and microbial levodopa metabolism. Trials of probiotics, fecal microbiota transplantation, and dietary interventions remain heterogeneous and have not established disease-modifying efficacy. Progress will require longitudinal studies in prodromal and subtype-defined populations, objective gastrointestinal measurements, integrated microbial, host-genetic and other multi-omics, mechanistic human and animal models, and clinical trials combining target-engagement markers with meaningful outcomes. Such an approach may enable precision gut-brain medicine for appropriately selected patients with PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},
}

@article {pmid42846143,
year = {2026},
author = {Yu, T and Nie, T and Mai, Q and Wang, L and Hu, Z and Wu, M and Pan, M and Liang, Y and Liu, H},
title = {Bibliometric analysis of dietary patterns in Parkinson's disease: from Mediterranean diet to emerging trends.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1954819},
pmid = {42846143},
issn = {1663-4365},
abstract = {BACKGROUND: Parkinson's disease (PD) is one of the fastest-growing neurological disorders. Treatments remain symptomatic, with no disease-modifying therapies available. Recent preclinical and epidemiological studies suggest that dietary patterns may influence PD pathology through the microbiota-gut-brain axis by modulating gut microbiota. However, evidence remains conflicting: some studies report protective effects of specific diets, while large-scale prospective studies find no significant associations. These discrepancies reflect differences in study design and dietary assessment and a lack of systematic understanding of the field. No bibliometric study has systematically analyzed this area. Therefore, this study uses bibliometric methods to map research hotspots and evolutionary trends and identify knowledge gaps.

METHODS: Systematic searches were conducted in the Web of Science Core Collection and Scopus databases to identify literature on dietary patterns in Parkinson's disease from inception to June 11, 2026. CiteSpace was used to perform bibliometric analyses, construct a knowledge map, and identify research hotspots and evolutionary trends.

RESULTS: A total of 424 publications were included. The top three most productive countries were the USA, China, and Italy, and the leading institutions included the NIH, Harvard University, and Johns Hopkins University. Key authors included Mark P. Mattson, Alberto Ascherio, and Xiang Gao. Current research hotspots are mainly "Mediterranean diet", "ketogenic diet", "caloric restriction", "gut microbiota", "gut-brain axis", and "oxidative stress". Emerging topics include "probiotic agent", "prebiotic agent", "fecal microbiota transplantation", and "mild cognitive impairment".

CONCLUSION: Dietary patterns may influence PD through synergistic mechanisms, with their roles in regulating oxidative stress, neuroinflammation, mitochondrial function, and gut microbiota progressively being revealed. The microbiota-gut-brain axis may represent an important pathway linking dietary factors to central nervous system function through microbial metabolites, immunomodulation, and neural signaling. Existing studies suggest potential associations between specific dietary patterns and PD risk or clinical outcomes; however, methodological heterogeneity and the predominantly observational evidence base have precluded consistent conclusions and limited clinical translation. Therefore, no specific dietary pattern can currently be recommended with confidence for the clinical management of PD. As a modifiable lifestyle factor, dietary patterns bridge metabolic dysregulation and neurodegeneration, and their integration into PD management remains a future direction.

https://osf.io/vgc9p, identifier VGC9P.},
}

@article {pmid42846262,
year = {2026},
author = {Zhang, C and Zhang, Q and Zhang, L and Chen, Y and Chen, D},
title = {The role of the gut-lung axis in persistent inflammation and disease progression in chronic obstructive pulmonary disease: mechanistic evidence and therapeutic implications.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1925745},
doi = {10.3389/fimmu.2026.1925745},
pmid = {42846262},
issn = {1664-3224},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/therapy/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology ; Disease Progression ; Animals ; *Lung/immunology/metabolism/microbiology ; Inflammation/immunology ; Dysbiosis ; },
abstract = {Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease worldwide, and the mechanisms underlying its persistent airway inflammation, systemic inflammation, and acute exacerbations remain incompletely understood. In recent years, the concept of the gut-lung axis has provided a new perspective for understanding the pathophysiological processes of COPD, suggesting that gut microbiota imbalance may participate in the regulation of pulmonary inflammation via this bidirectional pathway. This article systematically reviews the biological basis of the gut-lung axis, focusing on the mechanisms by which the gut microbiota influences pulmonary immune homeostasis through metabolic signals such as short-chain fatty acids, tryptophan derivatives, and bile acids, as well as through intestinal barrier maintenance, immune cell regulation, and microbe-associated inflammatory pathways. Current research indicates that COPD patients exhibit decreased gut microbiota diversity, reduced abundance of short-chain fatty acid-producing bacteria, and increased opportunistic pathogens, alterations correlated with decreased lung function, systemic inflammation, and the risk of acute exacerbations. This article further explores the potential mechanisms by which microbiota imbalance contributes to the persistence of pulmonary inflammation through processes such as disrupted microbial metabolic profiles, intestinal barrier damage, immune cell imbalance, and inflammasome activation, and evaluates potential intervention strategies targeting the gut-lung axis, including probiotics, dietary interventions, traditional Chinese medicine (TCM), and fecal microbiota transplantation (FMT). Overall, based on existing evidence, gut microbiota imbalance may participate in the persistence of chronic inflammation, acute exacerbations, and disease progression in COPD through the gut-lung axis, offering new insights for adjuvant therapy and individualized interventions in COPD. However, current evidence is still primarily derived from observational studies and preclinical research, and future research utilizing prospective cohorts, multi-omics integrative analyses, and randomized controlled trials is required to further validate its causal relationships, intervention effects, and clinical safety.},
}

Humans
*Pulmonary Disease, Chronic Obstructive/therapy/immunology/microbiology/metabolism
*Gastrointestinal Microbiome/immunology
Disease Progression
Animals
*Lung/immunology/metabolism/microbiology
Inflammation/immunology
Dysbiosis

@article {pmid42846731,
year = {2026},
author = {Chen, M and Su, Q and Sun, M and Zhang, H and Xu, J and Zhang, C and Wang, Y},
title = {Modulating the Gut-Ovarian Axis: Mechanistic Rationale and the Limits of Current Evidence for Probiotics in Female Reproductive Aging.},
journal = {Food science & nutrition},
volume = {14},
number = {10},
pages = {e72454},
doi = {10.1002/fsn3.72454},
pmid = {42846731},
issn = {2048-7177},
abstract = {Female reproductive aging is characterized by progressive follicular depletion, deterioration of oocyte quality, and endocrine decline, with oxidative stress, mitochondrial dysfunction, immune-inflammatory remodeling, and granulosa-cell loss contributing to ovarian functional deterioration. This critical narrative review, supported by a structured literature search, evaluates mechanistic, preclinical, and human evidence for probiotic and microbiota-targeted modulation of the gut-ovarian axis. The current evidence base remains predominantly preclinical. In premature ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), chemotherapy-induced ovarian injury, and reproductive-aging models, selected interventions have modified intestinal microbial ecology, barrier function, microbial metabolites, and systemic immune-metabolic-endocrine signaling, with model-specific effects on ovarian redox homeostasis, granulosa-cell survival, follicular development, mitochondrial function, and oocyte-related outcomes. Mechanistic support is strongest where gut dependency, metabolite supplementation, or related causal approaches have been demonstrated, but responses remain highly strain-, model-, dose-, route-, and host-dependent. Human trials in PCOS and menopause-related or reproductive settings have reported changes in selected metabolic, hormonal, menstrual, symptom, quality-of-life, and fertility-related outcomes; however, our structured literature and trial-registry searches did not identify a randomized human trial specifically designed to test whether probiotic or microbiota-targeted intervention slows the longitudinal physiological loss of ovarian reserve or delays physiological ovarian aging. Findings from disease models, fecal microbiota transplantation, or other experimental interventions should therefore not be equated with the efficacy of oral probiotic foods or supplements. Current evidence supports biological plausibility and translational potential rather than established ovarian anti-aging efficacy. Future studies should evaluate well-characterized oral strains using prespecified ovarian-aging-relevant endpoints, mechanistic biomarkers, and standardized safety assessment.},
}

@article {pmid42846861,
year = {2026},
author = {Kumar, M and Singh, P and Almohannadi, N and Al Khodor, S},
title = {Translational approaches in microbiome research: from functional mechanisms to next-generation therapeutics.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1943873},
doi = {10.3389/fmicb.2026.1943873},
pmid = {42846861},
issn = {1664-302X},
abstract = {Microbiome research has made substantial progress toward clinical translation over the past 2 decades, moving from associative observations toward mechanistic investigation, validation, and therapeutic intervention. This narrative review examines recent advances in the clinical application of microbiome research over the past 5 years, focusing on non-invasive microbiome-derived biomarkers and therapeutic strategies, including personalized probiotics and prebiotics, fecal microbiota transplantation (FMT), and engineered microbial therapeutics, while evaluating the strength of the supporting evidence. Microbiota-based treatments for recurrent Clostridium difficile infection are currently at the forefront of clinical translation, whereas applications in inflammatory, metabolic, neurological, and oncological disorders remain largely investigational. We further examine these translational barriers while highlighting opportunities to integrate microbiome data with systems biology and advanced analytics to improve clinical outcomes and advance precision medicine. By linking mechanistic discoveries with their current level of clinical development, this narrative review critically evaluates the available translational microbiome evidence, identifies key bottlenecks and unresolved knowledge gaps, and outlines priorities for the responsible integration of microbiome-based diagnostics and therapeutics into clinical practice.},
}

@article {pmid42848247,
year = {2026},
author = {Sagawa, T and Hirakawa, M and Nagashima, H and Fujikawa, K},
title = {Tumor microenvironment and gut microbiome in immunotherapy resistance in gastric cancer: clinical questions, biological mechanisms, and evidence-based therapeutic perspectives.},
journal = {Medical oncology (Northwood, London, England)},
volume = {43},
number = {11},
pages = {},
pmid = {42848247},
issn = {1559-131X},
mesh = {Humans ; *Stomach Neoplasms/immunology/microbiology/drug therapy/therapy/pathology ; *Tumor Microenvironment/immunology ; *Drug Resistance, Neoplasm/immunology ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Immunotherapy/methods ; },
abstract = {Immune checkpoint inhibitors (ICIs) have improved systemic therapy for advanced gastric and gastroesophageal junction cancer, yet primary and acquired resistance remain common and are incompletely explained by established tumor biomarkers. This narrative review evaluates the connected roles of the tumor microenvironment (TME), host immunity, and the gut microbiome in shaping ICI resistance in gastric cancer. We performed a structured PubMed search through 28 August 2026 and prioritized gastric cancer-specific clinical and translational evidence, supplemented by systematic reviews, meta-analyses, and mechanistically relevant studies from other tumor types when necessary. Within the gastric cancer TME, cancer-associated fibroblasts, myeloid cells, regulatory T cells, extracellular matrix remodeling, hypoxia, angiogenesis, and T-cell exhaustion can promote immune exclusion or dysfunction. Microbial diversity, microbial metabolites, antibiotics, proton pump inhibitors, defined live biotherapeutics, fecal microbiota transplantation, and diet may influence systemic antitumor immunity, but most human evidence is retrospective, cross-sectional, or derived from non-gastric cancers. Clinically, antibiotic stewardship, reassessment of unnecessary acid suppression, and nutritional optimization are reasonable supportive measures, whereas routine probiotic supplementation, Clostridium butyricum MIYAIRI 588 for ICI sensitization, and fecal microbiota transplantation remain investigational in gastric cancer. Future studies should integrate longitudinal exposures, serial TME profiling, stool metagenomics, medication use, nutritional status, and clinical outcomes. The TME-gut microbiome axis is therefore a biologically plausible framework for biomarker-guided research, but current evidence does not justify empiric microbiome-directed anticancer therapy in gastric cancer.},
}

Humans
*Stomach Neoplasms/immunology/microbiology/drug therapy/therapy/pathology
*Tumor Microenvironment/immunology
*Drug Resistance, Neoplasm/immunology
*Gastrointestinal Microbiome/immunology/drug effects
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
*Immunotherapy/methods

@article {pmid42849176,
year = {2026},
author = {Zucchi, E and Niccolai, E and De Maio, F and Cuoghi Costantini, R and Quaranta, G and Guarnaccia, A and Bibbò, S and Martinelli, I and Gianferrari, G and Simonini, C and Nannini, G and Lulli, M and Baldi, S and Bartolucci, G and Vicini, R and Capasso, M and Bisogni, G and Conte, A and Brunori, P and Cammarota, G and Paganoni, S and D'Amico, R and Amedei, A and Masucci, L and Mandrioli, J and , },
title = {Immune effects of faecal microbiota transplantation in amyotrophic lateral sclerosis: a pilot multicentre, randomised, masked, sham-controlled, proof-of concept trial.},
journal = {EBioMedicine},
volume = {133},
number = {},
pages = {106509},
doi = {10.1016/j.ebiom.2026.106509},
pmid = {42849176},
issn = {2352-3964},
abstract = {BACKGROUND: The gut microbiota modulates peripheral immunity, which is altered in amyotrophic lateral sclerosis (ALS). Faecal microbiota transplantation (FMT) may exert immunological effects, but its impact in ALS remains unclear.

METHODS: FETR-ALS was a multicentre, randomised, masked, sham-controlled proof-of-concept trial conducted at four Italian ALS centres. Adults with ALS of 18 months duration or less and forced vital capacity of at least 70% predicted were randomly assigned (2:1) to receive FMT or a sham procedure (SP). The intervention consisted of two nasojejunal administrations of screened-donor faecal suspension at baseline and month 6, without antibiotic preconditioning. The primary endpoint was change in circulating Tregs among CD4[+] T cells at 6 months. Secondary endpoints included safety, ALS Functional Rating Scale-Revised slope, respiratory and nutritional measures, survival, and exploratory biomarker profiles. Analyses followed the intention-to-treat principle.

CLINICALTRIALS: gov identifier: NCT03766321.

FINDINGS: Between 2020 and 2024, 43 individuals were screened and 42 were enrolled and randomly assigned to FMT (n = 28; mean age 56.1 years [SD 8.2]; 14 [50%] male) or SP (n = 14; 59.6 years [9.1]; eight [57%] male). Overall, 29 participants completed the second procedure and 6-month follow-up, and Treg measurements were available for 28. The primary outcome was not met: at 6 months, 8/18 (44%) participant receiving FMT versus 2/10 (20%) receiving SP achieved a ≥20% increase in circulating Tregs (odds ratio [OR] 3.20, 95% CI 0.59-25.36; p = 0.21). Mean Treg increase was 2.36 percentage points higher with FMT (95% CI 0.19-4.55; p = 0.04). ALSFRS-R declined by -1.07 points/month in the SP group and -0.76 points/month in the FMT group, with a between-group difference in monthly decline of 0.31 points/month favouring FMT (95% CI 0.11-0.51; p = 0.002). Conversely, at month 6, the MRC score was lower in the FMT group than in the SP group (0.75 versus 0.89; mean difference -0.13, 95% CI -0.26 to 0.00; p = 0.042). FMT was associated with 32 adverse events (12.5% severe) versus 14 (28.6% severe) in SP, mostly gastrointestinal or infectious.

INTERPRETATION: In this exploratory trial, FMT was not associated with major safety concerns. Although the primary endpoint was not met, FMT was associated with a modest increase in circulating Tregs.

FUNDING: Italian Ministry of Health.},
}

@article {pmid42849550,
year = {2026},
author = {Wang, Z and Zhang, H and Tian, P and Li, S and Li, L and Tian, K and Shi, X and Wu, C and Fan, Y and Lv, YE},
title = {The Gut-Lumbar Axis: A Comprehensive Review of Mechanisms, Clinical Evidence, and Future Therapeutic Perspectives.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {109667},
doi = {10.1016/j.phrs.2026.109667},
pmid = {42849550},
issn = {1096-1186},
abstract = {Low back pain (LBP) affects approximately 619 million people globally and is the leading cause of years lived with disability, yet the pathogenesis of chronic LBP remains incompletely understood despite extensive research into structural and biomechanical factors. Emerging evidence suggests that the gut microbiota, through its influence on systemic inflammation, immune regulation, metabolic homeostasis, and neuromodulation, plays a previously unrecognized role in lumbar spine pathology. While prior frameworks such as the "gut-disc axis" and "gut-spine axis" have addressed intervertebral disc degeneration or vertebral bone metabolism in relative isolation, we propose the "gut-lumbar axis" as an integrative framework that systematically unifies the intervertebral discs, vertebrae, paraspinal musculature, and neural structures of the lumbar spine within a single physiological and pathological continuum. This review synthesizes current evidence on the bidirectional communication between intestinal microbiota and lumbar spine health, covering intervertebral disc degeneration, chronic LBP, lumbar spinal stenosis, and vertebral osteoporosis. Multiple pathways linking gut dysbiosis to lumbar pathology are identified, supporting the gut-lumbar axis as a paradigm-shifting framework. However, large-scale longitudinal cohorts and well-designed randomized controlled trials are urgently needed to translate these findings into clinical practice. Microbiome-targeted therapies, including probiotics, dietary interventions, and fecal microbiota transplantation, hold promise as novel adjunctive strategies for managing chronic lumbar spine disorders, and key knowledge gaps for future investigation are highlighted.},
}

@article {pmid42477236,
year = {2026},
author = {Mohamed, ME and Cheng, S and Staley, C and Rashidi, A and Jurdi, NE and Holtan, SG and Jacobson, PA},
title = {Identification of Microbiome Associations with Tacrolimus Pharmacokinetics in Adult Hematopoietic Cell Transplantation Using Population Pharmacokinetic and Machine Learning.},
journal = {Pharmaceutical research},
volume = {43},
number = {9},
pages = {3125-3144},
pmid = {42477236},
issn = {1573-904X},
support = {1UM1TR004405/TR/NCATS NIH HHS/United States ; P30CA077598/CA/NCI NIH HHS/United States ; 1UM1TR004405/TR/NCATS NIH HHS/United States ; P30CA077598/CA/NCI NIH HHS/United States ; },
mesh = {*Tacrolimus/pharmacokinetics/administration & dosage ; Humans ; *Hematopoietic Stem Cell Transplantation ; *Immunosuppressive Agents/pharmacokinetics/administration & dosage ; Machine Learning ; Female ; Male ; Cytochrome P-450 CYP3A/genetics ; Middle Aged ; Adult ; *Gastrointestinal Microbiome ; Biological Availability ; Feces/microbiology ; Administration, Oral ; Aged ; },
abstract = {PURPOSE: Tacrolimus (TAC) is known for its high pharmacokinetic variability which cannot be fully explained by pharmacogenomic (PGx) and clinical variables. We identified gut microbiome associated with TAC pharmacokinetic variability in allogeneic hematopoietic cell transplant (HCT) recipients.

METHODS: In this observational study, metagenomic shotgun sequencing was used to analyze stool microbiome collected within ± 10 days from time of first oral TAC trough at steady state. TAC steady state concentrations (222 IV continuous infusion and 436 oral troughs) were modeled to estimate TAC clearance (CL) and oral bioavailability (F) using nonlinear mixed effects modeling. The effect of clinical covariates, PGx variants and concomitant medications on CL and F were evaluated. Machine learning was used to identify bacterial species associated with variability in F and CL. The identified species were incorporated into the final model, and simulations were conducted to estimate their clinical relevance on oral TAC troughs.

RESULTS: TAC population CL was 6.91 L/h and population F was 64.4%. TAC CL was increased in those with CYP3A5*1 genotype and reduced with voriconazole use and if estimated glomerular filtration rate < 60 ml/min/1.73 m[2]. TAC F increased with laxative use and decreased with corticosteroid use. Limosilactobacillus fermentum had the strongest positive effect on oral TAC troughs while Bacteroides uniformis had the strongest negative effect.

CONCLUSION: Gut microbiome contributes to the inter-patient variability in TAC CL and oral F.},
}

*Tacrolimus/pharmacokinetics/administration & dosage
Humans
*Hematopoietic Stem Cell Transplantation
*Immunosuppressive Agents/pharmacokinetics/administration & dosage
Machine Learning
Female
Male
Cytochrome P-450 CYP3A/genetics
Middle Aged
Adult
*Gastrointestinal Microbiome
Biological Availability
Feces/microbiology
Administration, Oral
Aged

@article {pmid42838172,
year = {2026},
author = {Cobuccio, L and Moser, K and Jacot, D and Kapel, N and Tsaousis, AD and Galperine, T},
title = {Clinical significance of Dientamoeba fragilis and Blastocystis: Lessons from clinical trials, cohort studies, and faecal microbiota transplantation - a narrative review.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2026.09.031},
pmid = {42838172},
issn = {1469-0691},
abstract = {BACKGROUND: The adoption of highly sensitive syndromic multiplex PCR panels led to an increase in Blastocystis and Dientamoeba fragilis detection, two of the most commonly identified intestinal protists worldwide. With positivity rates of 15-25% on syndromic gastrointestinal panels, a positive result frequently triggers antimicrobial treatment despite uncertain clinical significance.

OBJECTIVES: To synthesise multi-dimensional evidence on the pathogenicity of Blastocystis and D. fragilis from multiple lines of investigation and to propose a pragmatic clinical decision framework for interpreting positive test results.

SOURCES: A systematic search of PubMed/MEDLINE (inception to January 2026) was conducted using structured queries for Blastocystis and D. fragilis across thematic blocks: epidemiology, molecular diagnosis, pathogenicity mechanisms, clinical trials, faecal microbiota transplantation (FMT), and microbiome associations. No language restriction was applied. Study selection prioritised randomised controlled trials, prospective FMT cohorts, large-scale metagenomic analyses, and systematic reviews. Reference lists of retrieved articles were manually screened.

CONTENT: Current evidence suggests asymptomatic carriage is the biological norm for both organisms, and no specific subtypes, genotypes, or parasite load thresholds have been consistently linked to disease. Three placebo-controlled randomised controlled trials (RCTs) showed no treatment benefit: two conducted in paediatric populations and one an adult pilot study. FMT cohort studies demonstrate safe transmission without adverse events. Metagenomic analyses of nearly 57,000 individuals have identified an association between Blastocystis carriage, greater microbial diversity, and more favourable cardiometabolic profiles, although the direction and causality of these relationships remain unclear.

IMPLICATIONS: In immunocompetent hosts, detection of Blastocystis or D. fragilis does not indicate disease; for Blastocystis in particular, carriage should be regarded as an ecological marker of the intestinal microbiota. A clinical decision algorithm is proposed in which reassurance is the default, treatment is reserved for exceptional circumstances (severe immunosuppression or chronic unexplained symptoms after thorough exclusion of alternative diagnoses), and clinical response, not PCR clearance, serves as the only meaningful endpoint.},
}

@article {pmid42839257,
year = {2026},
author = {Wirth, U and Vilchez-Vargas, R and Fuchs, F and Schardey, J and Koch, N and Kühn, F and Renz, BW and Werner, J and Schulz, C and Andrassy, J},
title = {The biliary microbiome in symptomatic cholelithiasis: a prospective comparison across distinct bacterial niches.},
journal = {BMC microbiology},
volume = {26},
number = {1},
pages = {},
pmid = {42839257},
issn = {1471-2180},
support = {CS-076//Munich Clinician Scientist Program/ ; },
mesh = {Humans ; Prospective Studies ; Female ; *Cholelithiasis/microbiology ; *Bacteria/classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Bile/microbiology ; Saliva/microbiology ; *Microbiota ; Male ; Aged ; Middle Aged ; DNA, Bacterial/genetics/chemistry ; Sequence Analysis, DNA ; *Biliary Tract/microbiology ; Adult ; DNA, Ribosomal/genetics/chemistry ; },
abstract = {BACKGROUND: Cholelithiasis is highly prevalent in the Western world and frequently requires surgical or endoscopic intervention. However, the composition and role of the biliary microbiome remain poorly understood. This study aimed to characterize and compare bacterial communities of the biliary niche with saliva and faeces in patients with cholelithiasis.

METHODS: In this prospective observational study, patients with symptomatic cholecystolithiasis, chronic or acute cholecystitis, and choledocholithiasis were included. Bacterial community composition was characterized across bile, gallstone, saliva, and faecal samples using 16 S rRNA-based sequencing. Community-level and genus-level differences were assessed according to anatomical niche and clinical diagnosis, complemented by compositional sensitivity analyses and predicted functional profiling.

RESULTS: A total of 227 samples from 81 patients were analyzed. Bacterial community composition was strongly determined by anatomical niche (PERMANOVA, R² = 0.273, P < 0.001), with bile and gallstone communities being most closely related but remaining significantly distinct (R² = 0.146, q < 0.001). Diagnosis-associated differences were predominantly confined to the biliary compartments and remained significant after adjustment for age, explaining 7.9% of variation in bile and 14.1% in gallstones, whereas no significant associations were observed in saliva or faeces. Compositionally aware analysis with continuous age adjustment identified robust diagnosis-associated signals in bile, including Escherichia/Shigella, Leptotrichia, Serratia, and Pseudomonas. Biliary communities were characterized by taxa including Enterococcus, Escherichia/Shigella, Serratia, and Pseudomonas. In bile, Escherichia/Shigella increased with inflammatory disease, while Pseudomonas decreased; compositionally aware analysis confirmed diagnosis-associated differences for Escherichia/Shigella, Leptotrichia, and Serratia. Predicted bacterial functions showed even stronger anatomical compartmentalization (R² = 0.507, P = 0.001), whereas diagnosis-associated functional differences were limited to two MetaCyc pathways in gallstones. Sensitivity analyses provided no evidence that prolonged antibiotic exposure significantly affected biliary bacterial diversity or community composition.

CONCLUSION: This comprehensive multi-niche analysis demonstrates pronounced taxonomic and predicted functional compartmentalization of bacterial communities across saliva, bile, gallstones, and faeces in patients with cholelithiasis. Diagnosis-associated alterations were predominantly observed within biliary niches, with Escherichia/Shigella emerging as a consistent taxon associated with inflammatory biliary disease. These findings identify anatomical niche as a major determinant of bacterial community structure and support disease-associated alterations within the biliary microbiome.

TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinische Studien) DRKS00030566 (retrospectively registered 20250818).},
}

Humans
Prospective Studies
Female
*Cholelithiasis/microbiology
*Bacteria/classification/genetics/isolation & purification
RNA, Ribosomal, 16S/genetics
Feces/microbiology
Bile/microbiology
Saliva/microbiology
*Microbiota
Male
Aged
Middle Aged
DNA, Bacterial/genetics/chemistry
Sequence Analysis, DNA
*Biliary Tract/microbiology
Adult
DNA, Ribosomal/genetics/chemistry

@article {pmid42839679,
year = {2026},
author = {Zhang, C and Li, M and Li, T and Zang, X and Shi, H and Liu, Y and Zhang, C and Zhao, J and Zhai, Q and Chen, W and Tian, F},
title = {A Postbiotic-Inducing Ganoderma applanatum Polysaccharide Repairs the Intestinal Barrier via a Phocaeicola vulgatus - Tridecylic Acid Axis.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e78105},
doi = {10.1002/advs.78105},
pmid = {42839679},
issn = {2198-3844},
support = {2022YFF1100203//National Key Research and Development Project/ ; 32425044//National Natural Science Foundation of China/ ; 32502150//National Natural Science Foundation of China/ ; 2025ZB702//Jiangsu Funding Program for Excellent Postdoctoral Talent/ ; //Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province/ ; },
abstract = {Intestinal barrier dysfunction is a pathological hallmark of ulcerative colitis (UC), yet therapeutic strategies that precisely restore epithelial integrity remain limited. Here, we identified four distinct polysaccharide fractions from Ganoderma applanatum (GAPs) and pinpointed GAP2 as the principal bioactive component that significantly ameliorates DSS-induced colitis and intestinal barrier injury. Furthermore, experiments using germ-free mice and fecal microbiota transplantation show that the barrier-repairing efficacy of GAP2 depends on the gut microbiota and their metabolic outputs. This indicates that GAP2 acts as a microbiota-directed modulator, exerting health benefits by enriching Phocaeicola vulgatus and tridecylic acid. P. vulgatus degrades GAP2 via GH16, facilitating fatty-acid metabolism to generate tridecanoic acid (absent in the mutant), which may activate the Rho/CDC42 pathway in intestinal epithelial cells to promote tight-junction assembly, thereby restoring barrier integrity. Notably, a meta-analysis of UC patient cohorts revealed that both the abundance of P. vulgatus and its capacity for tridecylic acid biosynthesis were significantly decreased. Our findings establish GAP2 as a potent postbiotic inducer that repairs the intestinal barrier via a potential P. vulgatus-tridecylic acid-Rho/CDC42 axis. This work highlights the therapeutic potential of targeting this newly identified microbe-metabolite-signaling axis for the treatment of UC and related mucosal inflammatory disorders.},
}

@article {pmid42840357,
year = {2026},
author = {Huang, Q and Xiang, H and Liu, Q and Zhang, Y and Zou, J and Gao, Z and Yang, L and Zeng, H and Liu, J},
title = {Fecal microbiota transplantation and peri-stoma microbiome management in patients with intestinal stomas: from mechanisms to clinical translation.},
journal = {Frontiers in oncology},
volume = {16},
number = {},
pages = {1913974},
pmid = {42840357},
issn = {2234-943X},
abstract = {BACKGROUND: Fecal diversion-induced dysbiosis in the defunctioned intestinal segment represents a common pathogenic basis for diversion colitis, anastomotic leakage, and long-term metabolic sequelae in patients with permanent stomas. This review proposes the novel concept of "Peri-stoma Microbiome Management (PSMM)" and critically evaluates the clinical evidence for fecal microbiota transplantation (FMT), defined microbial consortia, bacteriophages, and postbiotics. It is important to emphasize that PSMM is a proposed conceptual framework; most of its components have not been prospectively validated in stoma patients.

MAIN BODY: The core pathological process involves a dramatic reduction in butyrate-producing obligate anaerobes, depriving colonocytes of their primary energy substrate. In experimental models, butyrate depletion impairs mitochondrial function and autophagic flux, with subsequent NLRP3 inflammasome activation; whether this pathway operates identically in the defunctioned human colon remains to be directly investigated. Collagenolytic pathobionts such as Enterococcus faecalis may expand under antibiotic pressure and secrete matrix metalloproteinase-9 that degrades anastomotic extracellular matrix. However, anastomotic leakage is a multifactorial complication, involving tissue ischemia, tension, patient comorbidities, and microbial factors. The PSMM framework encompasses four phases: (I) pre-stoma creation microbial pre-habilitation and risk prediction; (II) microbiota monitoring and intervention during stoma maintenance; (III) pre-reversal targeted decolonization using bacteriophages and engineered microbiota reconstruction; and (IV) long-term metabolic maintenance for permanent stoma carriers. Bacteriophages show promise for precision decolonization but face significant challenges, including bacterial resistance, narrow host range, manufacturing complexity, and regulatory barriers. Multi-omics monitoring remains aspirational due to high costs, long turnaround times, and lack of clinical integration.

CONCLUSION: The PSMM framework provides a structured conceptual approach for integrating microbiome-targeted strategies into the care of patients with intestinal stomas. However, most interventions remain investigational and require validation in adequately powered randomized trials.},
}

@article {pmid42840760,
year = {2026},
author = {Shi, L and Wang, P and Wu, B and Huang, C},
title = {The Plasticene Paradigm: Microplastics, Gut Dysbiosis, and Food Allergy - A Critical Commentary.},
journal = {Journal of asthma and allergy},
volume = {19},
number = {},
pages = {625708},
pmid = {42840760},
issn = {1178-6965},
abstract = {BACKGROUND: The increasing prevalence of food allergy (FA) in industrialized regions cannot be fully explained by traditional hygiene and biodiversity frameworks, suggesting the involvement of new environmental triggers. Microplastics (MPs), which are dietary contaminants now consistently found in human biological samples, have been proposed as a potential threat to gut-immune balance. However, direct evidence for this link in humans is still lacking.

MAIN BODY: This commentary critically examines and advances the "Plasticene Paradigm", which hypothesizes that dietary MP exposure disrupts the beneficial relationship between the host and its microbiota, thereby promoting the development of FA through microbiota-dependent mechanisms. The central mechanism proposed involves MP-induced dysbiosis, characterized by a reduction in short-chain fatty acid (SCFA) -producing bacteria. This reduction subsequently impairs the differentiation of regulatory T cells (Tregs), disrupts the balance between Th2 and Treg cells, and compromises the integrity of the intestinal barrier. While studies involving fecal microbiota transplantation in animal models offer causal evidence under experimental conditions, this evidence primarily comes from studies using supraphysiological doses of pristine polymers (mg/kg/day range). These doses exceed mass-based estimates of human daily intake (μg/kg/day range) by several orders of magnitude, although direct quantitative comparison is complicated by the use of heterogeneous exposure metrics (mass-based vs particle-count-based) across different estimation approaches. This significant difference in dosage fundamentally limits the applicability of these findings to human exposure levels found in the environment. We identify four obstacles to translating these findings: dose relevance, exposure complexity, challenges in model extrapolation, and analytical constraints. These barriers currently prevent drawing definitive conclusions about human risk.

CONCLUSION: The current evidence, which is predominantly preclinical, is constrained by issues of dose relevance, exposure complexity, and gaps in model extrapolation, with human data largely showing only associations. We propose a three-pronged research agenda: (I) establishing prospective birth cohorts with specific biomonitoring for polymers; (II) conducting mechanistic studies using environmentally relevant MP mixtures in FA models; and (III) developing microbiome-targeted interventions as needed. This framework aims to transform the Plasticene Paradigm from a hypothesis-driven mechanistic narrative into one supported by a stronger evidence base. This evidence may ultimately inform public health policy, food safety regulations, and precise prevention strategies for FA in an era of widespread plastic contamination.},
}

@article {pmid42833873,
year = {2026},
author = {Haque, M and Lesker, TR and Rolle-Kampczyk, U and Segers, A and De Vos, WM and Molinaro, A and Basavanapura, T and Chen, Y and Backhaus, M and Mohamed, MR and Jiang, L and Salih, Q and Candels, L and Henricsson, M and Bielecka, A and Lang, S and Tacke, F and Hengstler, JG and Schneider, CV and Demir, M and Strowig, T and von Bergen, M and Schneider, KM and Trautwein, C},
title = {Microbiota-host genetic interactions modulate MASLD risk in PNPLA3[I148M] carriers via ceramides and are reversible by targeted microbial interventions.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2026-338178},
pmid = {42833873},
issn = {1468-3288},
abstract = {BACKGROUND: The factors that determine when genetic susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD) progresses to clinically significant liver injury remain incompletely understood.

OBJECTIVE: We investigated whether disruption of the intestinal host-microbiota interface acts as a contextual modifier that amplifies PNPLA3[I148M] -associated hepatic injury.

DESIGN: We used a dual-hit mouse model combining hepatic Pnpla3[I148M] -expression with Nlrp6-deficiency, a model of impaired intestinal mucosal homeostasis, under western-diet conditions. Multi-omics profiling, including metagenomics, metabolomics and transcriptomics, was integrated with analyses in human cohorts (Lifelines, Charité MASLD, Human Phenotype Project). Microbiota-dependent effects were examined using faecal microbiota transplantation (FMT), antibiotic-mediated depletion and targeted intervention with Akkermansia muciniphila or its membrane protein Amuc_1100.

RESULTS: In mice, the combination of Pnpla3[I148M] expression and impaired intestinal sensing synergistically exacerbated gut-barrier dysfunction and bacterial encroachment, accompanied by increased portal levels of microbiota-associated metabolites, including long-chain ceramides (Cer(d18:1/16:0), Cer(d18:1/18:0)) and bile acids. These changes were associated with hepatic mitochondrial stress and inflammatory responses. Human carriers with advanced MASLD displayed microbial and metabolic signatures consistent with increased gut-derived metabolic signalling. Restoration of eubiotic microbiota via FMT or Amuc_1100 treatment improved intestinal barrier integrity and attenuated hepatic lipid accumulation in experimental models.

CONCLUSION: These findings suggest that gut-derived signals resulting from a disrupted intestinal barrier may act as modifiers of PNPLA3[I148M] -clinical penetrance by amplifying downstream metabolic and inflammatory responses. By identifying these pathways linking environmental context to genetic susceptibility, this study highlights the host-microbiota interface as a potential target for strategies aimed at limiting MASLD progression in genetically at-risk individuals.},
}

@article {pmid42834983,
year = {2026},
author = {Jiang, H and Wang, Y and Tian, Q and Sui, Y and Sun, J and Chen, L and Liu, X and Tan, N},
title = {Bifidobacterium pseudolongum enriched by arctigenin ameliorates cough variant asthma via the acetate-aryl hydrocarbon receptor-interleukin-33 axis.},
journal = {Journal of pharmaceutical analysis},
volume = {16},
number = {9},
pages = {101610},
pmid = {42834983},
issn = {2214-0883},
abstract = {Gut microbiota dysbiosis is significantly associated with the onset and progression of cough variant asthma (CVA). Targeting and improving gut microbiota dysbiosis may serve as a promising strategy for CVA. Suhuang antitussive capsule (SH) is the sole clinically approved traditional Chinese patent medicine specifically indicated for managing CVA. Herein, we initially identified arctigenin (AG) as one of the effective components detected and preliminarily screened from SH for its potential in treating CVA. AG significantly ameliorates ovalbumin (OVA)-induced CVA symptoms, alleviates gut dysbiosis, and improves intestinal barrier function. Specifically, AG alleviates CVA symptoms in a gut microbiota-dependent manner, as demonstrated by antibiotic treatment and fecal microbiota transplantation (FMT). 16S rDNA sequencing revealed that AG treatment could notably enrich the commensal bacterium Bifidobacterium pseudolongum (B. pseudolongum), which is typically reduced in CVA. The mono-colonization with B. pseudolongum also showed a reduction in CVA severity. Gas chromatography-mass spectrometry (GC-MS) metabolomic analysis identified acetate as the key and main serum metabolite induced by B. pseudolongum. We demonstrated that acetate enters pulmonary circulation and activates the aryl hydrocarbon receptor (AHR). Validation using AHR antagonists, siRNA knockdown, chromatin immunoprecipitation (ChIP) assays, luciferase reporter experiments, and molecular docking confirmed that acetate-mediated AHR activation suppresses interleukin-33 (IL-33) secretion from lung epithelial cells, thereby preventing CVA progression. These findings suggest AG, one of the effective components in SH, exhibits prebiotic-like effects to alleviate CVA and highlight the potential of targeting specific gut microbiota species for CVA treatment.},
}