Inflammatory bowel disease (IBD) affects nearly 7 million individuals worldwide and includes cases of Chrohn’s Disease and ulcerative colitis. This chronic inflammatory disorder affects the gastrointestinal tract. While the exact cause of the disease remains to be elucidated, there seems to be environmental risk factors, such as gut microbiome alterations, that are associated with IBD. Alterations in the gut-microbiome have also been linked to psychiatric diseases via the gut-brain axis. Not surprisingly, depression and anxiety are often reported in patients with IBD.
Dr. Li-Ping Zhao and colleagues looked into the central and peripheral kynurenine pathway (KP) alterations in a mouse model of colitis and recently published their findings in Frontiers in Immunology. In this study, the researchers used dextran sulfate sodium (DSS) to induce colitis in mice. DSS-induced colitis was associated with decreased serum tryptophan levels and increased serum kynurenine (KYN), suggesting increased activation of the KP. Interestingly, KYN was also significantly increased in cerebral cortex tissue of animals with DSS-induced colitis. Activation of the KP was likely indolamine-2,3-dioxygenase (IDO-1) driven, as IDO-1 mRNA levels were increased in both the liver and brain following DSS-treatment. Furthermore, IDO-1 is significantly increased in peripheral blood mononuclear cells and colon tissue samples taken from ulcerative colitis patients. DSS-induced colitis was also associated with phenotypic changes in astrocytes and a decrease in serum kynurenic acid levels however, there were no significant changes observed in the microglial phenotypes. Taken together, these data suggests that colitis has a central impact and may lead to increased neurotoxicity. Additionally, the researchers investigated the microbial alterations following DSS-induced colitis. Not surprisingly, colitis was associated with intestinal flora changes, with increased abundance of seven bacterial species and decreased abundance of one compared to control animals. Interestingly, the altered gut microbiota was associated with increased tryptophan metabolism. This study demonstrates that gut microbiota and tryptophan metabolism play a role in IBD and may contribute to the psychiatric comorbidities of IBD.