Aida Habtezion, MD, Stanford University, Sidhartha R. Sinha, MD Stanford University and Justin Sonnenburg, PhD Stanford University, ($200,000) for Secondary Bile Acids Modulate Intestinal Inflammation

Research Abstract

The cause of Inflammatory Bowel Disease (IBD) is unknown, but intestinal bacteria—involved in the production of molecules that impact health—are widely accepted to play a key role. A significant proportion of IBD patients with pouches (surgically created rectums after the diseased colon is removed) continue to have inflammation similar to their previous disease, whereas non-IBD patients with pouches rarely have inflammation. Our results show key differences in the composition of an important class of bacteria-modified molecules known as secondary bile acids (SBAs) between these groups and that these SBAs reduce inflammation. We have also found that these SBA differences may be explained by reduced composition of specific gut bacteria. The research proposed will improve our understanding of the role of SBAs in controlling gut inflammation. Restoring the microbiome by correcting these compositional differences or administration of SBAs hold potential as new therapeutic targets for IBD.

Iliyan D. Iliev, PhD, Weill Medical College of Cornell University, Inga Peter, PhD, Icahn School of Medicine at Mount Sinai, and Jean-Frédéric Colombel, MD, PhD, Icahn School of Medicine at Mount Sinai, ($250,000) for The role of Inflammatory Bowel Disease in the fungal microbiota transmission from pregnant women to the offspring.

Research Abstract

The intestines are home to a community of not only bacteria, but also fungi, which are involved in several immune-mediated inflammatory diseases, including IBD. It is unknown how fungi appear in the intestine and whether they are part of the intestinal microflora early in life. In this project, we will explore whether gut fungi can be transferred from mother to the newborn. We will further study the composition of the fungal community in babies born to mothers with IBD to understand whether specific fungi can be transferred from the mother to the babies and potentially contributing to disease later in life.

Gwendalyn Randolph, PhD, Washington University, Saurabh Mehandru, MD, Icahn School of Medicine, Mount Sinai, Daniel Mucida, PhD, Rockefeller University, ($300,000) for Toward identifying the unique pathology that explains Ulcerative Colitis distribution

Research Abstract

According to the Montreal classification, ulcerative colitis (UC) disease scope varies from how much of the colon is affected, with lesser colon involvement called proctitis (E1) and extensive disease called pancolitis (E3). These differing extents impact rates of hospitalization, chance of colectomy, and cancer risk. When the extent of UC is limited (E1 or E2) there is always a sharp demarcation between macroscopically involved and uninvolved areas, although the underlying cause(s) of the clear separation between healthy and unhealthy tissues is unknown. We suspect that this line is determined by antibody-mediated damage to the nervous system that is connected to the colon, because nerves organization in bands around the colon is consistent with the disease pattern. This proposal will investigate this remarkable feature of UC, trying to determine the underlying causes, which may lead to a better understanding of the drivers of disease and progression.