(P19-045-25) High-Fiber Diet Exacerbates DSS-Induced Murine Colitis Due to Shifts in Microbial Metabolism of Complex Carbohydrates

Objectives: To functionally profile the gut microbial metabolism of complex carbohydrates in ulcerative colitis (UC) and its effects on the host. We hypothesized that administration of high-fiber diet during UC would exacerbate colitis by disturbing the gut microbial utilization of complex carbohydrates in highly inflamed gut environment.

Methods: We used a Dextran Sodium Sulfate (DSS) induced colitis in C57BL6/j male and female mice (n=8). DSS was administered at 2% via drinking water along with a custom made high-fiber chow containing 75 g/kg inulin and 75 g/kg pectin. Gut contents and tissue were collected for downstream analyses. 16S rRNA sequencing was performed using Illumina MiSeq. Activity-Based protein profiling (ABPP) was performed using an in-house synthesized chemical probe for glycoside hydrolases and along with metaproteomics was analyzed via LC-MS. GC-MS was used for short-chain fatty acid (SCFA) detection in serum.

Results: To our surprise, mice receiving high-fiber diet and DSS showed 94% lethality in response to the treatment, while mice receiving DSS alone had 100% survival. In contrast to this lethality report, histological evaluation of the colon lining revealed a significantly lower level of inflammation and intestinal damage in the high-fiber DSS mice when compared to the mice on DSS alone. Gut microbial richness and density were reduced upon combination of DSS and high-fiber diet. Functional characterization of carbohydrate active enzymes by ABPP revealed specific glycoside hydrolase families that suffered significant functional change in colitic mice fed high-fiber diet.

Conclusions: This work reveals key microbial enzymes involved in degradation of complex carbohydrates, some of which are impaired in the inflamed gut of mice with colitis.

Funding Sources: James R. Schofield Endowment