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Session: Polyphenols: Metabolism and Health (Oral 18)

(OR18-07-24) The Anti-colitic Activity of Phlobaphenes and Anthocyanins in Humanized IL-10 -/- Mice Is Independent of Ulcerative Colitis-Associated Dysbiosis

Monday, July 1, 2024
9:12 AM – 9:24 AM CT
Location:  W183

    Presenting Author(s)

  • Jose A. Haro Reyes, PhD (c) (he/him/his)

    Research Assistant
    Purdue University
    West lafayette, Indiana, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • LR

    Lavanya Reddivari, PhD

    Associate Professor
    Purdue University
    West Lafayette, Indiana, United States

Objectives: Gut bacterial dysbiosis is one of the most relevant factors interplaying in the development of Ulcerative Colitis (UC), a chronic disorder characterized by gut inflammation and impairment of the gut barrier function. Flavonoid-rich dietary sources protect the gut barrier integrity. However, the role of bacterial dysbiosis on the anti-colitic properties of the flavonoids is not fully understood. This study aimed to assess the effect of non-UC and UC-associated microbiota on the anti-colitic activity of phlobaphenes (PHLO) and/or anthocyanins (ANTH).

Methods: Six-week-old gnotobiotic IL-10 -/- mice [C57BL/6] were colonized with human fecal microbiota from three non-UC and three UC patients. Mice were assigned to three dietary treatments; a purified control diet (Diet P), 25% maize near-isogenic line expressing ANTH (Diet C), and 25% maize expressing ANTH and PHLO (Diet D). Seven weeks later, mice were given 1.5% dextran sodium sulfate (DSS) in drinking water to induce colitis. The weight of the digestive tract organs was measured. FITC-dextran assayed intestinal permeability. Relative expression levels of colonic inflammatory markers, tight junction proteins, and mucin were analyzed by RT-qPCR.

Results: DSS increased the colon weight /length ratio by 29 and 25% in mice with UC- or non-UC-associated microbiota, respectively. Furthermore, DSS reduced cecum size by 46% and elevated the expression of IL-1β and IL-6 in mice with non-UC microbiota. Muc2 expression was reduced by DSS in mice with UC microbiota.

Although dysbiosis did not exacerbate the expression of NF-κB, IL-1β, Muc-2, and IL-6 in mice in Diet P, biomarkers were affected by the flavonoids depending on the donors’ microbiota. Diet D reduced the expression of NF-κB compared to C, regardless of the gut microbiota. However, IL-1β and IL-6 expressions were higher in diet D in non-UC microbiota mice.

Conclusions: UC induction with DSS and the anti-colitic activity of PHLO and ANTH is suggested regardless of dysbiosis but in a donor-dependent manner. Results are preliminary as part of a staggered experiment, where expression of other inflammatory markers, tight junction proteins, barrier integrity assessment, and microbial composition are currently in progress.

Funding Sources: USDA-NIFA award 2019-67017-29258