The new geography of the human gut could push healthcare forwards

The term obese describes a person who’s very overweight, with a lot of body fat. Obesity is believed to account for 80-85 percent of the risk of developing type 2 diabetes. — © Digital Journal

A new study has used genomic sequencing for the first time to redefine the regions of the small intestine. This comes from a consortium of researchers based at Cedars-Sinai, the University of California, San Francisco (UCSF), Harvard University, and the Weizmann Institute of Science in Israel.

The scientists conducted a study to determine where individual nutrients are absorbed in the small intestine. From this the researchers identified the molecular markers that define five distinct intestinal regions.

The human small intestine measures more than 20 feet long and it represents an important area for medical study. Scientists have long sought to understand the biological patterns along the length of the small intestine that allow it to function efficiently.

The organ is divided into three portions: the duodenum, the jejunum and the ileum. These areas have served as the common basis of scientific knowledge. Instead the investigators defined five regions within the mouse and human small intestine, distinct from the three that scientists had previously described. Hence, this study questions the suitability of these regions and instead presents a new regional organization of the intestine.

The molecular data has enabled scientists to better understand the cellular and molecular processes that occur in the small intestine and what goes wrong in gastrointestinal diseases. It is of particular medical importance that each of the five domains is associated with different aspects of nutrient absorption, and each exhibits distinct responses to changes in diet.

The investigators examined 30 portions of the small intestine in multiple species. This allowed for a view of intestinal geography. The investigators also used genomic sequencing technology to determine the precise locations where genes involved in nutrient absorption were expressed along the length of the small intestine.

In particular, different cellular ‘neighbourhoods’ have been located within the small intestine and these execute different intestinal functions. Furthermore, the differences account for different gastrointestinal diseases and the likelihood of individuals developing such pathologies.

Diseases of interest include intestinal cancers, ileitis [a type of inflammatory bowel disease], and celiac disease. To gain insights, the investigators generated a predictive model of key factors that may maintain regional expression of nutrient absorption genes.

It is hoped the study will lead to technological advances in regenerative medicine by providing information that can be used to regenerate regional nutrient absorption in portions of the intestine damaged by bowel resection surgeries and disease.

The results appear in the journal Nature Cell Biology, with the research paper titled “Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains.”