期刊
CELLS
卷 11, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/cells11060968
关键词
alcohol; bile acid; microbiota; bacteria; liver; pectin; fiber
类别
资金
- INSERM
- Universite Paris-Saclay, Fondation pour la Recherche Medicale (FRM), National French Society of Gastroenterology (SNFGE)
- Association Francaise pour l'Etude du Foie (AFEF)
- Inserm Transversal Programme on Microbiota
- Biocodex
- Laboratory of Excellence LERMIT
- Agence Nationale de la Recherche [ANR-10-LABX-33]
- Ligue contre le Cancer (equipe labellisee)
- Agence National de la Recherche (ANR)-Projets blancs [AMMICa US23/CNRS UMS3655]
- Association pour la Recherche sur le Cancer (ARC)
- Association Ruban Rose
- Canceropole Ile-de-France
- Fondation pour la Recherche Medicale (FRM)
- Gustave Roussy Odyssea
- European Union
- Fondation Carrefour, Institut National du Cancer (INCa)
- Inserm (HTE)
- Institut Universitaire de France
- LabEx Immuno-Oncology [ANR-18-IDEX-0001]
- Leducq Foundation
- Mark Foundation
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- IdEx Universite de Paris [ANR-18-IDEX-0001]
Pectin improves alcohol-induced liver disease in mice by modifying the bile acid cycle through effects on the intestinal microbiota and enhanced bile acid excretion.
Reshaping the intestinal microbiota by the ingestion of fiber, such as pectin, improves alcohol-induced liver lesions in mice by modulating bacterial metabolites, including indoles, as well as bile acids (BAs). In this context, we aimed to elucidate how oral supplementation of pectin affects BA metabolism in alcohol-challenged mice receiving feces from patients with alcoholic hepatitis. Pectin reduced alcohol liver disease. This beneficial effect correlated with lower BA levels in the plasma and liver but higher levels in the caecum, suggesting that pectin stimulated BA excretion. Pectin modified the overall BA composition, favoring an augmentation in the proportion of hydrophilic forms in the liver, plasma, and gut. This effect was linked to an imbalance between hydrophobic and hydrophilic (less toxic) BAs in the gut. Pectin induced the enrichment of intestinal bacteria harboring genes that encode BA-metabolizing enzymes. The modulation of BA content by pectin inhibited farnesoid X receptor signaling in the ileum and the subsequent upregulation of Cyp7a1 in the liver. Despite an increase in BA synthesis, pectin reduced BA serum levels by promoting their intestinal excretion. In conclusion, pectin alleviates alcohol liver disease by modifying the BA cycle through effects on the intestinal microbiota and enhanced BA excretion.
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