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

ABSTRACT:

Ulcerative colitis (UC)-associated intestinal fibrosis represents a serious and currently untreatable complication, highlighting an urgent need for novel therapeutic strategies. This study investigates the therapeutic potential of Jiayi Huatu Decoction (JHD), a traditional Chinese herbal formula and provides substantial innovation by identifying a previously unexplored “gut microbiota–metabolite” axis through which JHD alleviates colonic fibrosis. We believe our study makes a significant contribution to the literature. We provide the first demonstration that JHD can selectively enrich two distinct beneficial bacteria, Faecalibaculum rodentium and Akkermansia muciniphila. Furthermore, we elucidate a novel mechanistic cascade in which F. rodentium-derived butyrate reduces the pro-fibrotic metabolite 2-piperidone by inhibiting copper amine oxidase 3 (AOC3), while A. muciniphila-produced 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (LysoPE16:0) decreases taurocholic acid levels through the activation of farnesoid X receptor (FXR), ultimately suppressing extracellular matrix deposition and inflammatory signaling.

INSTRUMENT(S): Liquid Chromatography MS - alternating - hilic, Liquid Chromatography MS - alternating - reverse-phase

PROVIDER: MTBLS13875 | MetaboLights | 2026-02-09

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13875_LC-MS_alternating_hilic_metabolite_profiling.txt	Txt
	a_MTBLS13875_LC-MS_alternating_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13875_LC-MS_alternating_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13875_LC-MS_alternating_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1-/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273- B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.

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

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