A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin
Category
Published on
Type
journal-article
Author
Do-Hyun Kim and Yilin Wang and Haerin Jung and Rachael L. Field and Xinya Zhang and Ta-Chiang Liu and Changqing Ma and James S. Fraser and Jonathan R. Brestoff and Steven J. Van Dyken
Citation
Kim, D.-H., Wang, Y., Jung, H., Field, R. L., Zhang, X., Liu, T.-C., Ma, C., Fraser, J. S., Brestoff, J. R., & Van Dyken, S. J. (2023). A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin. Science, 381(6662), 1092–1098. https://doi.org/10.1126/science.add5649
Abstract
Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.