National Institute of Allergy and Infectious Diseases 5R00AI173660-04

Dietary regulation of type 2 immunity and inflammation in the gut

This NIH-funded project investigates how diet and microbiota influence type 2 immunity and inflammation in the gut, focusing on dietary fiber's effects mediated by microbial metabolites and immune cells, to improve therapies for gastrointestinal disorders.

Description

Understanding the role of environmental factors including signals derived from the diet and microbiota is key to improving therapeutic and intervention strategies for gastrointestinal disorders including inflammatory bowel diseases (IBD) and inflammation-associated colorectal cancer (CRC). Dietary fiber can exert immunoregulatory effects through microbial fermentation products including short chain fatty acids (SCFAs). Preliminary studies identified that an inulin-rich high fiber diet triggers colonic eosinophilia in a microbiota-dependent manner, exacerbating disease outcomes in murine models of intestinal damage and CRC. These diet-induced responses are associated with microbiota-derived bile acids and activation of mesenchymal stromal cells (MSCs) and group 2 innate lymphoid cells (ILC2s). The project aims to determine how bile acids regulate cytokines and eosinophilia, investigate eosinophils' contribution to intestinal damage, and identify microbial metabolic pathways involved in diet-induced inflammation.

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