Intestinal Epithelial Remodeling in Homeostasis and Inflammation

  • Ileum IHC
  • heatmap
  • EM

Gastrointestinal Control of Metabolism

A large body of data have linked the gastrointestinal (GI) tract to the etiology of obesity, diabetes, and related metabolic disorders. Some of the most innovative and efficient approaches to treat these diseases involve the manipulation of the GI tract. The GI is not only an organ system for digesting food and absorbing nutrients, it is also a major endocrine organ, secreting GI hormones in control of various metabolic processes (Fig. 1). In addition, the GI tract is also a lymphoid organ, which modulates the microbial control of host metabolism.

Microbiota-host interactions

The microbial community (microbiota), comprising of bacteria, viruses, archaea, fungi, and protozoa, resides on various anatomical areas of the human body. It is estimated that the ratio of microbes to human cells is close to 1:1, emphasizing the notion that the microbiota, as an "organ", has significant impact on host physiology. Most of the microbes are "commensal", benefiting the fitness of the host in metabolism, immune function, and neural development. Many bioactive microbial products, such as short-chain fatty acids (SCFAs), play key functions in microbiota-host interactions.

Intestinal inflammation

In genetically susceptible humans, inappropriate activation of immune cells and the resulting chronic inflammation in response to infiltrating commensal and/or pathogenic microbial species lead to inflammatory bowel disease (IBD). Intestinal epithelial cells (IECs) establish a barrier between the luminal and the internal environment, placing IECs at the center of interactions between the mucosal immune system and luminal antigens/metabolites (Fig. 2). A healthy and robust layer of IECs is required for intestinal homeostasis. Defects in IECs cause intestinal inflammation in animal models and are associated with IBD in humans.

We aim to characterize how the GI tract relays signals from food, microbiota and parasites to regulate body weight, glucose metabolism, and immune response.

Related publications:

1. 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.
2. Huang Y, Lia SC, Hu J, Ruan HB, Guo HM, Zhang HH, Wang X, Pei YF, Pan Y, Fang C. (2018). Gut Microbiota Profiling in Han Chinese with Type 1 Diabetes. Diabetes Research and Clinical Practice. doi: 10.1016/j.diabres.2018.04.032.


Fig. 1: Enteroendocrine cells and hormones

Fig. 2: Microbiota, IECs, and immune cells—a trio in IBD