Patients with inflammatory bowel disease (IBD) have dysfunctions in gut motility (the movement of muscles in the gastrointestinal tract). Currently, most available therapeutics developed to directly target the gut fail to stabilize symptoms, suggesting that dysfunctions in gut motility could arise from pathological changes occurring outside the gut. Intriguingly, gut motility problems also occur at […]

Our gut is constantly exposed to environmental harms, such as bacteria and dietary products, among others. The epithelium layer of our intestinal tract, which is the most exposed to the external world, contains a variety of immune cells, which likely play an important role in patrolling and defending our intestine. However, how these cells protect […]

NOD2 was the first and to do date the most frequent gene associated with inflammatory bowel disease. The NOD2 protein functions as a sensor of bacteria by binding molecules (peptidoglycans) shed from the bacterial cell wall. The IBD mutations in NOD2 result in its inactivation or partial loss of function. In 2019 we reported that […]

Microbiota small molecules correlate with IBD pathogenesis, yet the molecular mechanisms behind remain elusive. We recently developed gene manipulation tools in multiple gut Clostridia commensals, and by mutating the responsible gene and mono-colonizing germ-free mice with the mutant, we can switch specific microbiota metabolites on/off in vivo and found that metabolites derived from Clostridia amino […]

Besides the brain, the gastrointestinal tract has the highest number of neurons in the entire body. The enteric nervous system (ENS) is often referred to as the second brain as it commands all manner of intestinal function, from nutrient absorption to defecation control. In patients suffering from IBD, the ENS undergoes major disruption resulting in […]

Up to 15% of patients with ulcerative colitis (UC) will require surgery, the most common of which is the total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA). Since 1980, the ‘J’ pouch has revolutionized the lives of thousands of patients, providing restoration of intestinal continuity and avoidance of a permanent end ileostomy. Unfortunately, pouchitis is […]

Colonization of the infant gut by commensal bacteria profoundly influences immune development and can thus have significant long-term consequences: promoting durable tolerance to environmental antigens or driving IBD. Despite the importance of this process for health, how immune responses to the microbiota are regulated during early life remain a significant gap in our knowledge. We […]

While pathogenic fungi have been identified in the gut of Crohn’s disease (CD) patients, their role in triggering gut inflammation is unclear. We recently showed that a high proportion of CD patients have a unique fungal species, D. hansenii, in their inflamed gut mucosa. We used mouse models to identify that key immune cell types […]

Diet is thought to be a major environmental factor contributing to inflammatory bowel disease (IBD) and represents a non-invasive path to improve this debilitating condition. To leverage diet to treat IBD the precise ways that dietary components influence development or healing of inflammation need to be determined. We discovered that different dietary protein sources have […]

How do immune responses of the intestinal lining contribute to inflammatory bowel diseases (IBD)? The goals of this project are to determine how cells of the intestinal epithelium are “hardwired” to respond to immune stimuli and how stable changes to these responses are related to IBD. It is known that multiple inflammatory factors produced by […]