Cell host & microbe, 2021-06, Vol.29 (6), p.988-1001.e6
2021
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- Autor(en) / Beteiligte
- Titel
- Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation
- Ist Teil von
- Cell host & microbe, 2021-06, Vol.29 (6), p.988-1001.e6
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Intestinal Paneth cells modulate innate immunity and infection. In Crohn’s disease, genetic mutations together with environmental triggers can disable Paneth cell function. Here, we find that a western diet (WD) similarly leads to Paneth cell dysfunction through mechanisms dependent on the microbiome and farnesoid X receptor (FXR) and type I interferon (IFN) signaling. Analysis of multiple human cohorts suggests that obesity is associated with Paneth cell dysfunction. In mouse models, consumption of a WD for as little as 4 weeks led to Paneth cell dysfunction. WD consumption in conjunction with Clostridium spp. increased the secondary bile acid deoxycholic acid levels in the ileum, which in turn inhibited Paneth cell function. The process required excess signaling of both FXR and IFN within intestinal epithelial cells. Our findings provide a mechanistic link between poor diet and inhibition of gut innate immunity and uncover an effect of FXR activation in gut inflammation. [Display omitted] •Diet-induced obesity results in Paneth cell dysfunction in humans and mice•Consumption of western diet leads to Clostridium-mediated deoxycholic acid conversion•Deoxycholic acid activates both FXR and type I IFN pathways•Both FXR and type I IFN pathways are essential in triggering Paneth cell defects Small intestinal Paneth cells are gatekeepers of gut innate immunity. Liu et al. identified a link between consumption of high fat, high sugar diet (western diet; WD) and Paneth cell dysfunction. The mechanisms involve WD-associated microbiota conversion of bile acids, which activate both FXR and type I interferon pathways.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1931-3128eISSN: 1934-6069DOI: 10.1016/j.chom.2021.04.004Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8192497
- Format
- –
- Schlagworte
- Animals, Bile Acids and Salts - metabolism, cell-intrinsic, Cells, Cultured, Diet, High-Fat - adverse effects, Diet, Western - adverse effects, Disease Models, Animal, Gastrointestinal Microbiome - drug effects, Gene Expression Profiling, high fat diet, Humans, Immunity, Innate - drug effects, Interferon Type I - metabolism, Intestinal Mucosa - metabolism, metabolism, Mice, Mice, Inbred C57BL, microbiota, myeloid cells, obesity, Obesity - metabolism, organoids, Paneth Cells - drug effects, Paneth Cells - metabolism, Receptors, Cytoplasmic and Nuclear - metabolism, Signal Transduction, transcriptomics