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Exposure to ultra violet B light on the skin modulates intestinal homeostasis in mice and humans

University of British Columbia

Ultraviolet B (UVB) light phototherapy has been successfully used to treat cutaneous disorders. In contrast, little is known about its systemic immunomodulatory effects, and if UVB light exposure on the skin is able to influence the gastrointestinal barrier and the intestinal microbiome. This thesis research investigates the influence of cutaneous UVB light exposure on the microbiome in humans, as well as vitamin D independent effects on the murine gastrointestinal environment during health and disease. The results from a clinical pilot study in healthy women indicate that three sub-erythemal UVB light exposures within the same week significantly improves serum vitamin D concentrations and is able to modulate the microbiome composition of those who started the study with vitamin D insufficiency. UVB light exposures in individuals who have been taking vitamin D supplementation over the winter months did not show any significant change in microbiome composition. The results suggest that the increase in serum vitamin D is responsible for taxa specific modulation of the microbiome, predominantly in the Lachnospiraceae genera. We also investigated if, and how cutaneous UVB light exposure affects the gastrointestinal environment in mice. C57BL/6 mice were repeatedly exposed to a sub-erythemal dose of UVB light which strongly attenuated concurrent DSS-induced colitis. This treatment was not associated with elevated production of vitamin D, but instead induced increased release of microbiome-derived acetate and aryl hydrocarbon receptor (Ahr) ligands, and subsequent Ahr activation as measured by downstream enzyme CYP1A1 activity. Chronic UVB light exposure also led to increased differentiation of intestinal goblet cells and other secretory epithelial subtypes in the colon and ileum. These responses to UVB light, including protection against colitis were abrogated in Ahr deficient mice. Similarly, stool metabolites from UVB exposed mice promoted goblet cell differentiation in colon derived murine organoids. This study demonstrates that exposure to UVB light induces the release of Ahr ligands that promote the differentiation of secretory epithelial cells, thereby protecting against colitis. The results from this thesis research indicate that cutaneous UVB light exposure affects the intestinal environment. Future studies should investigate the feasibility of clinical application of UVB phototherapy.

Text

2020-10-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/76264

Experimental Medicine

University of British Columbia

UBCV

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