Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation.
Mohammad ArifuzzamanTae Hyung WonHiroshi YanoJazib UddinElizabeth R EmanuelElin HuWen ZhangTing-Ting LiWen-Bing JinAlex GrierSanchita Kashyapnull nullChun-Jun GuoFrank C SchroederDavid ArtisPublished in: The Journal of experimental medicine (2024)
Innate lymphoid cells (ILCs) can promote host defense, chronic inflammation, or tissue protection and are regulated by cytokines and neuropeptides. However, their regulation by diet and microbiota-derived signals remains unclear. We show that an inulin fiber diet promotes Tph1-expressing inflammatory ILC2s (ILC2INFLAM) in the colon, which produce IL-5 but not tissue-protective amphiregulin (AREG), resulting in the accumulation of eosinophils. This exacerbates inflammation in a murine model of intestinal damage and inflammation in an ILC2- and eosinophil-dependent manner. Mechanistically, the inulin fiber diet elevated microbiota-derived bile acids, including cholic acid (CA) that induced expression of ILC2-activating IL-33. In IBD patients, bile acids, their receptor farnesoid X receptor (FXR), IL-33, and eosinophils were all upregulated compared with controls, implicating this diet-microbiota-ILC2 axis in human IBD pathogenesis. Together, these data reveal that dietary fiber-induced changes in microbial metabolites operate as a rheostat that governs protective versus pathologic ILC2 responses with relevance to precision nutrition for inflammatory diseases.
Keyphrases
- oxidative stress
- nk cells
- physical activity
- weight loss
- induced apoptosis
- diabetic rats
- end stage renal disease
- endothelial cells
- newly diagnosed
- neoadjuvant chemotherapy
- chronic kidney disease
- signaling pathway
- squamous cell carcinoma
- binding protein
- ejection fraction
- gene expression
- microbial community
- ms ms
- high glucose
- machine learning
- genome wide
- radiation therapy
- lymph node
- drug induced
- big data