Embedded throughout the gastrointestinal system is an extensive array of neurons that coordinates nearly all activities involved in digestion, gut motility, and response to noxious stimuli. These cells make up the enteric nervous system (ENS) and transmit signals from the gut to the brain, but are rare and fragile, making them difficult to isolate and study.
A team led by researchers at the Broad Institute of MIT and Harvard and Massachusetts General Hospital has now overcome these challenges with new methods that they developed to generate a single-cell map of the ENS in humans and mice.
By analyzing gene activity in these individual neurons, the scientists infer that neurons in the gut are communicating with a variety of other cell types, including immune cells. They also found that key genes associated with disease are expressed in these cells.
The findings suggest that the ENS is a central hub linking the intestinal, immune, and central nervous systems, and plays an important role in allergic, inflammatory, and motility disorders of the gut, as well as diseases affecting the brain.
Studying these kinds of neuro-immune interactions is the next phase of the Food Allergy Science Initiative — a multi-institution research collaboration, housed at Broad, that seeks to understand the biological basis of food allergies and encourage the development of new treatments. The initiative helped support the new study.
“By learning what’s happening in the ENS, we can better understand how the system communicates with epithelial, immune, and other cells, and generate new ways to treat dysfunction within the whole system,” said Broad core institute member Ramnik Xavier, co-senior author of the study, director of the Immunology Program and co-director of the Infectious Disease and Microbiome Program at Broad, investigator at Massachusetts General Hospital, and Kurt Isselbacher Professor of Medicine at Harvard Medical School.
The work appears this week in Cell, led by co-first authors Eugene Drokhlyansky, Christopher Smillie, and Nicholas Van Wittenberghe of the Klarman Cell Observatory (KCO) at the Broad Institute.
