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Jiayi Huatu Decoction mitigates intestinal fibrosis via a gut microbiota–metabolite axis

ABSTRACT: Ulcerative colitis (UC), a chronic inflammatory bowel condition, lacks effective treatments. We aimed to examine the therapeutic potential of Jiayi Huatu Decoction (JHD), a traditional Chinese formula, in treating UC in mice, focusing on its modulation of gut microbiota and metabolites. JHD significantly alleviated intestinal fibrosis and chronic inflammation. Mechanistically, JHD promoted beneficial gut bacteria, specifically Faecalibaculum rodentium and Akkermansia muciniphila. Integrated metabolomics and proteomics identified excessive 2-piperidone and taurocholic acid accumulation as colonic fibrosis and inflammation drivers. F. rodentium-derived butyric acid suppressed copper amine oxidase 3, reducing 2-piperidone production, while A. muciniphila-derived 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (LysoPE16:0) activated farnesoid X receptor (FXR) to decrease taurocholic acid. Genetic ablation of FXR abolished LysoPE16:0 anti-fibrotic and anti-inflammatory activities. JHD exerts therapeutic effects by modulating gut microbiota and supporting F. rodentium and A. muciniphila propagation, which synergistically regulate extracellular matrix deposition and cell adhesion signaling pathways through specific metabolites, offering a strategy for UC treatment.

ORGANISM(S): Mus Musculus

SUBMITTER: Dongmei Chen

PROVIDER: PXD074286 | iProX | Mon Feb 09 00:00:00 GMT 2026

REPOSITORIES: iProX

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Project description:Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date, only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo. Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays. Results. UC patients showed a dysbiotic microbiota with lower diversity and more species belonging to Actinobacteria and Proteobacteria phyla. On the contrary, their healthy siblingsM-bM-^@M-^Y microbiota contained more bacteria from the Lachnospiracea and Ruminococcaceae family than did healthy individuals . Sixty-three host transcripts significantly correlated with bacterial genera in healthy individuals whereas only 43 and 32 correlated with bacteria in healthy and UC siblings from discordant pairs, respectively. Several transcripts related to oxidative and immune responses were differentially expressed between unaffected and UC siblings. Conclusion. A loss of crosstalk between gut microbiota and host was highlighted in UC patients. This defect was also striking in healthy siblings from discordant pairs, as was the lower biodiversity within the microbiota. Our results suggest disease-relevant interactions between host transcriptome and microbiota. Moreover, unusual aerobic bacteria were noticed in UC mucosal microbiota, whereas healthy siblings from discordant pairs had higher percentages of potentially beneficialusual commensal bacterial species. Paired samples (twins) were analyzed to obtain data independent of genetic variation

Project description:Objective: Ulcerative colitis (UC) is a chronic disease with rising incidence and unclear etiology. The application of mass spectrometry-based post-genomic analysis methods shall support the development of molecular biomarker signatures providing status information with regard to UC pathomechanisms. Design: Pathomechanisms characteristic for UC were assessed by proteome profiling of human tissue specimen, obtained from five distinct colon locations each of 12 patients. Systemic disease-associated alterations were investigated by mass spectrometry-based multi-omics analyses comprising proteins, metabolites and eicosanoids of plasma obtained from UC patients during disease and upon remission in comparison to healthy controls. Results: Proteome profiling results identified colitis-associated activation of neutrophils, macrophages, B- and T-cells, platelets, fibroblasts and endothelial cells and indicated hypoxic stress, as well as a general reduction of mitochondrial proteins accompanying the establishment of apparent healing-promoting activities as well as scar formation. While the immune cells mainly contributed pro-inflammatory proteins, the colitis-associated epithelial cells, fibroblasts, endothelial cells and platelets predominantly formed anti-inflammatory and healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulation of bile acids, eicosanoids and gut microbiome-derived metabolites. Upon remission, several, but not all, molecular candidate biomarker levels recovered to normal levels. These findings may indicate that pathomechanisms related to gut functions, gut microbiome status, microvascular damage and metabolic dysregulation associated with hypoxia may do not resolve uniformly upon remission. Conclusions: The establishment of disease-associated biomarker profiles related to molecular UC pathomechanisms may support the establishment of bioassays with improved prognostic power aiding individualized therapy.

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Jiayi Huatu Decoction mitigates intestinal fibrosis via a gut microbiota–metabolite axis

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