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Cotton, Sophie Anne

University of British Columbia

Crohn’s disease and ulcerative colitis, collectively termed inflammatory bowel disease (IBD), are chronic and incurable diseases of the gastrointestinal tract. Beyond the gastrointestinal tract, IBD patients exhibit high rates of hormonally driven sexual, reproductive, and psychiatric disorders. For instance, delayed puberty is reported in up to 85% of pediatric IBD patients, and sexual dysfunction is reported in up to 60% of adult female patients and up to 94% of adult male patients. Further, psychiatric illness is two to three times as prevalent in IBD patients compared to the general population. Previously, systemic sex steroid levels were thought to be exclusively controlled by the hypothalamic-pituitary-gonadal axis. However, recent research has identified gut microbes capable of degrading androgens and reactivating estrogens in a clinically significant manner. Based on these findings, we proposed that the gut microbiota could play a role in driving the high prevalence of neuroendocrine comorbidities observed in IBD. Specifically, we hypothesized that IBD-like alterations to the murine gut would induce sexual, reproductive, and psychiatric effects like those seen in IBD patients. To test this hypothesis, we used the well-known dextran sodium sulfate (DSS) model of IBD to disrupt the murine gut microbiota and induce inflammation at specific developmental time points, and measured the effect on the gut, systemic sex steroid levels, reproductive development, brain cell morphology and behavior. Confirming our hypothesis, we found that DSS induced inflammation reshapes the composition of the gut microbiota, compromises the integrity of the gut epithelium, impedes the development of the seminal vesicles, and causes changes in sex-specific behavior. In contrast, DSS did not appear to disrupt systemic sex steroid levels, affect the timing of pubertal onset, cause damage to the reproductive organs or alter mating behavior. Taken together, these results suggest that DSS inflammation selectively impacts certain aspects of the gut-endocrine-brain axis in IBD while leaving others unaffected. This points to the need for further research that can take a multi-system approach to investigating the complex and nuanced interplay between the gut microbiota, immune system, endocrine system, reproductive organs, brain and behavior in IBD.

Text

2024-01-15

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87275

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/