Metabolic Adaptation for Intestinal Homeostasis

Ileum IHC

The gastrointestinal (GI) tract is an organ system not only absorbing nutrients from food, but also secreting a large body of endocrine hormones, and possessing a rich defensive arsenal of immune cells. The organ is constantly challenged by the changing environment to balance its primary functions of nutrient uptake and host defense. Inability of the GI tract in adapting to environmental changes leads to diseases such as obesity, malabsorption, autoimmune, and inflammation.  

The commensal microbiota, as an "organ", impacts host physiology by producing microbe-associated molecular patterns and bioactive metabolites. Metabolic maladaptations in intestinal stem cells, epithelial cells, and mucosal immune cells to luminal antigens/metabolites cause intestinal inflammation in animal models and are associated with inflammatory bowel disease (IBD) in humans. We aim to characterize metabolic mechanisms by which the GI tract relays signals from food, commensal microbiota, and pathogens to regulate host metabolism and immunity.

Related publications:

1. Zhao M, Ren K, Xiong X, Xin Y, Zou Y, Maynard JC, Kim A, Battist AP, Koneripalli N, Wang Y, Chen Q, Xin R, Yang C, Huang R, Yu J, Huang Z, Zhang Z, Wang H, Wang D, Xiao Y, Salgado OC, Jarjour NN, Hogquist KA, Revelo XS, Burlingame AL, Gao X, von Moltke J, Lin Z, Ruan HB. (2022). Epithelial STAT6 O-GlcNAcylation drives anti-helminth immunity via a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C. Immunity. 55(4), 623–638. DOI: 10.1016/j.immuni.2022.03.009.
2. Zhao M, Ren K, Xiong X, Cheng M, Zhang Z, Huang Z, Han X, Yang X, Alejandro EU, Ruan HB. (2020). Protein O-GlcNAc modification links dietary and gut microbial cues to the differentiation of enteroendocrine L cells. Cell Reports. 32(6): 108013. doi: /10.1016/j.celrep.2020.108013.
3. Zhao M, Xiong XW, Ren K, Xu B, Cheng M, Sahu C, Wu K, Nie Y, Huang Z, Blumberg RS, Han X, Ruan HB. (2018). Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation. EMBO Molecular Medicine. doi: 10.15252/emmm.201708736.

Microbiota, IECs, and immune cells—a trio in IBD