ArticleProceedings of the National Academy of Sciences of the United States of America2016
High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 3 of them syntheses that pooled it.
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Who cites it
132 citing papers in PubMed, 3 syntheses or guidelines pooled it, 243 citations in OpenAlex.
- Bibliometric analysis of theFrontiers in microbiology · 2025Pooled it
- Prebiotics for people with cystic fibrosis.The Cochrane database of systematic reviews · 2023Pooled it
- Probiotics for people with cystic fibrosis.The Cochrane database of systematic reviews · 2020Pooled it
- Use of Faecal Transplantation with a Novel Diet for Mild to Moderate Active Ulcerative Colitis: The CRAFT UC Randomised Controlled Trial.Journal of Crohn's & colitis · 2022Trial
- Trial
- Single-nucleus multi-omics analysis of mouse small-intestinal Lgr5+ cell populations reveals Foxa3-induced Paneth cell-lineage differentiation.Communications biology · 2026Article
- Journey through the gut-inflammation axis in polycystic ovary syndrome: the microbiota's role in shaping inflammatory pathways.Molecular and cellular biochemistry · 2026Review
- Alterations in the gut microbiota are associated with changes in intestinal antibody production in KK-Ay mice developing type 2 diabetes.Frontiers in immunology · 2026Article
- Brush border intermicrovillar adhesion limits bacteria attachment to the small intestine brush border.bioRxiv : the preprint server for biology · 2025Article
- Gut microbiota and associated metabolites: key players in high-fat diet-induced chronic diseases.Gut microbes · 2025Review
- Disentangling the impact of obesity, diet, host factors, and microbiota on small intestinal antimicrobial peptide expression.Gut microbes · 2025Article
- Bovine Adipocyte-Derived Exosomes Transport LncRNAs to Regulate Adipogenic Transdifferentiation of Bovine Muscle Satellite Cells.Animals : an open access journal from MDPI · 2025Article
- Liraglutide upregulates the Cftr gene and regulates the mucus transcriptome profile in Brunner's glands in mice.Clinical and translational medicine · 2025Article
- Peroxisome Proliferator-Activated Receptors (PPARs): A Themed Issue in Honor of Prof. Walter Wahli.Biomolecules · 2025Article
- Dietary protein intake and overall diet quality in adults with cystic fibrosis following elexacaftor/tezacaftor/ivacaftor therapy.The British journal of nutrition · 2025Observational
- Substitution of polysorbates by plant-based emulsifiers: impact on vitamin D bioavailability and gut health in mice.Communications biology · 2025Article
- Macronutrients as Regulators of Intestinal Epithelial Permeability: Where Do We Stand?Comprehensive reviews in food science and food safety · 2025Review
- Analysis of causal effects on metabolic syndrome and inflammatory bowel disease: a Mendelian randomization study.Diabetology & metabolic syndrome · 2025Article
- Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease.Biomedicines · 2025Review
- The role of intestinal microbiota and its metabolites in the occurrence and intervention of obesity.Frontiers in microbiology · 2025Review
72 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum-which is usually described as free of bacteria-became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ-deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.