ArticleJCI insight2020
Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by high-fat feeding.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Pleiotropic roles of microbial bile acid metabolism in intestinal health and diseases.Cell host & microbe · 2026Review
- Paneth cells as orchestrators of epithelial barrier defense and emerging therapeutic targets in inflammatory bowel disease.Seminars in immunopathology · 2026Review
- The Causal Role of Bile Acids in Cancers of the Digestive System.Biomedicines · 2026Review
- Gut-Heart Axis in HFpEF: The Emerging Role of Microbiome-Driven Inflammation and Endothelial Dysfunction.Biomolecules · 2026Review
- Gut microbiota-epigenetic interactions in systemic aging: mechanistic drivers for endocrine and reproductive network remodeling and therapeutic modulation.Frontiers in aging · 2026Review
- Role of the gut microbiota in hypertriglyceridemic acute pancreatitis: potential mechanisms and therapeutic implications.Therapeutic advances in gastroenterology · 2026Review
- Gut microbiome in metabolic dysfunction-associated steatotic liver disease and associated hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025Review
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- NECTIN4 regulates the cell surface expression of CD155 in non-small cell lung cancer cells and induces tumor resistance to PD-1 inhibitors.Cancer immunology, immunotherapy : CII · 2025Article
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- ABL1‒YAP1 axis in intestinal stem cell activated by deoxycholic acid contributes to hepatic steatosis.Journal of translational medicine · 2024Article
- Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- The role of bile acids in human aging.Medical review (2021) · 2024Article
- Human α-Defensin 5International journal of molecular sciences · 2023Article
- Maternal Western diet mediates susceptibility of offspring to Crohn's-like colitis by deoxycholate generation.Microbiome · 2023Article
- Intestinal epithelial autophagy is required for the regenerative benefit of calorie restriction.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Decreased Paneth cell α-defensins promote fibrosis in a choline-deficient L-amino acid-defined high-fat diet-induced mouse model of nonalcoholic steatohepatitis via disrupting intestinal microbiota.Scientific reports · 2023Article
- Liver's influence on the brain through the action of bile acids.Frontiers in neuroscience · 2023Review
- Multifaceted involvements of Paneth cells in various diseases within intestine and systemically.Frontiers in immunology · 2023Review
- High-fat diet induces intestinal mucosal barrier dysfunction in ulcerative colitis: emerging mechanisms and dietary intervention perspective.American journal of translational research · 2023Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
High-fat feeding (HFF) leads to gut dysbiosis through unclear mechanisms. We hypothesize that bile acids secreted in response to high-fat diets (HFDs) may act on intestinal Paneth cells, leading to gut dysbiosis. We found that HFF resulted in widespread taxonomic shifts in the bacteria of the ileal mucosa, characterized by depletion of Lactobacillus and enrichment of Akkermansia muciniphila, Clostridium XIVa, Ruminococcaceae, and Lachnospiraceae, which were prevented by the bile acid binder cholestyramine. Immunohistochemistry and in situ hybridization studies showed that G protein-coupled bile acid receptor (TGR5) expressed in Paneth cells was upregulated in the rats fed HFD or normal chow supplemented with cholic acid. This was accompanied by decreased lysozyme+ Paneth cells and α-defensin 5 and 6 and increased expression of XBP-1. Pretreatment with ER stress inhibitor 4PBA or with cholestyramine prevented these changes. Ileal explants incubated with deoxycholic acid or cholic acid caused a decrease in α-defensin 5 and 6 and an increase in XBP-1, which was prevented by TGR5 antibody or 4PBA. In conclusion, this is the first demonstration to our knowledge that TGR5 is expressed in Paneth cells. HFF resulted in increased bile acid secretion and upregulation of TGR5 expression in Paneth cells. Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by HFF.
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