(P03-030-23) Anti-Colitic Activity of Phlobaphenes and Anthocyanins in Humanized IL-10 -/- Mice With Bacterial Dysbiosis

Objectives: Ulcerative colitis (UC) is a colonic inflammatory disorder onset by an interplay of genetics, environment, the mucosal immune system, and gut microbial dysbiosis. Flavonoid rich diets possess anti-colitic effects. However, the individual and synergic contributions of the flavonoids, their interactions with the food matrix, and the impact of bacterial dysbiosis on the anti-colitic effects require further research. This study aimed to assess the effect of the human UC-associated microbiota on the anti-colitic properties of phlobaphenes (PHLO) and anthocyanins (ANTH) in a whole food matrix.

Methods: Six-week-old Germ-free IL-10 -/- mice [C57BL/6] were colonized with human fecal microbiota from UC patients. They were assigned to 4 dietary treatments and a purified control diet (Control). The diets were substituted with 25% maize near-isogenic lines (NILs), developed to express PHLO and/or ANTH (Diet A: no flavonoids; B: PHLO, C: ANTH, D: both). After 7 weeks the mice were exposed to 1.5% dextran sodium sulfate (DSS) in the drinking water for 6 days prior to sacrifice to induce colitis. Digestive tract organs were collected. Intestinal permeability was assayed by FITC-dextran. The relative expression of colonic inflammatory markers, tight junction proteins, and mucin were analyzed by RT-qPCR.

Results: Body weight loss was observed after DSS application. Higher liver weights (12%) and lower cecum weights (14 - 28%) were observed in mice given the maize diets compared to the control diet.  Diets A and B aggravated the DSS-induced increase in gut permeability (2 and 7-fold), but Diet D decreased the permeability (2-fold) compared to the control diet. IL-6 expression was higher in diets containing flavonoids. The expression of Muc2, a gene related to mucin production in the gastrointestinal tract, was higher in Diet D followed by C and B.

Conclusions: A synergistic anti-colitic activity of phlobaphenes and anthocyanins is suggested, implying underlying mechanisms of interaction. Results are preliminary from few subjects as part of a staggered experiment, where expression of other inflammatory markers and comparisons with healthy gut bacterial controls are currently in progress.

Funding Sources: USDA-NIFA award 2019