The Intestinal Adaptation Laboratory at St. Louis Children’s Hospital seeks to understand the mechanisms through which the intestine adapts to massive intestinal loss.
Multiple human conditions exist in which a large proportion of the intestine needs to be surgically removed or is lost due to injury, inflammation or interruption of blood supply. Once the intestine is removed, the remaining bowel senses this acute loss and tries to compensate by a process termed adaptation.
This adaptive response consists of increases in cellular proliferation within the mucosa as well as a slight bit of growth in intestinal length and caliber. During this time, patients clinically require intravenous nutrition to supplement what cannot be absorbed entirely by the gastrointestinal tract.
A full adaptation response is achieved when patients are able to tolerate full feedings by mouth and no longer need supplemental intravenous nutrition. In many circumstances, the adaptation response is incomplete, and many of these patients require a lifetime of parenteral nutrition and its allied complications.
The main thrust of the Intestinal Adaptation Laboratory is to more fully understand this response and thereby be able to enhance it. Ultimately, growing the bowel back will permit patients to achieve a more normal lifestyle and avoid the complications associated with intravenous nutrition.
The laboratory is led by Brad W. Warner, MD, and Jun Guo, PhD. This team blends sophisticated molecular biology techniques with clinically focused relevant applications. The technology utilizes transgenic, knockout and mutant mice in a unique intestinal resection surgical model. In addition, laser capture microdissection (LCM) microscopy is used to study adaptation in isolated cells of the small intestine.
Our specific research projects include:
- EGF has been established as a growth factor to stimulate intestinal adaptation; we are currently testing the efficacy of a soybean-based recombinant EGF on intestinal adaptation.
- How does angiogenesis contribute to intestinal adaptation following small bowel resection?
- Recently, we have discovered intestinal resection is associated with fatty liver, shifting microbiome in the gut, altered fasting blood sugar levels, abnormalities in glucose tolerance testing, and systemic inflammation, which we termed resection-associated metabolic syndrome (RAMS). We are actively pursuing the mechanism for RAMS.
- Type 2 immunity is a critical immune response against helminths invading mucosal sites. It plays a critical role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea. Intestinal tuft cells initiate the process by expressing IL-25 upon parasite infection. We have discovered that the mTORC1 signaling pathway, specifically Raptor protein in enterocytes, is required for relaying parasitic cues to initiate type 2 immune response. We are actively studying the mechanism of type 2 immunity in the small intestine and are utilizing that knowledge to transform intestinal adaptation.