Exacerbation of colitis by impaired microbial catabolism of sorbitol.

Sorbitol is a sugar alcohol that is not absorbed very well in our bodies. It is usually broken down in the gut by a type of bacteria called Clostridia. When these bacteria are not there, sorbitol accumulates and that leads to increased osmotic stress for the cells lining our intestines. Our cells have many defense mechanisms to protect themselves against osmotic stress. However, these mechanisms may lead to increased inflammation. Although sorbitol consumption triggers osmotic stress, a potential role of sorbitol in the progression of Inflammatory Bowel Disease (IBD) has not been investigated. Therefore, our goal is to find out how consumption of sugar alcohols by gut bacteria protects the host against osmotic stress that can aggravate colitis. Specifically, we will determine whether sorbitol-induced osmotic stress can trigger colonic inflammation when Clostridia are absent. Next, we will study how sorbitol consumption aggravates colonic inflammation when mice are exposed to environmental risk factors for IBD. Finally, we will investigate whether feeding mice a Clostridia species, called Anaerostipes caccae, can protect against sorbitol-induced inflammation.