(P18-001-25) Fiber Type Impacts Fiber Tolerance in UC-Associated Microbiota Transplanted Mice

Objectives: Ulcerative colitis (UC) is a chronic inflammatory disease confined to the colon and rectum. Although dietary fibers modulate gut inflammation via short-chain fatty acid (SCFA) production, patients with UC are often advised to limit their fiber intake during flare-ups due to poor tolerance. This study aims to use mice colonized with UC-associated microbiota to evaluate the effects of four dietary fibers: High Methoxyl Pectin (HMP), Chicory Inulin (ChIn), Resistant Maltodextrin (RMD), and Wheat Bran (WB). The goal is to identify fiber physicochemical property(ies) that dictate efficacy and tolerance in UC.

Methods: 6-week-old IL-10 KO germ-free mice were randomly assigned to a 15% fiber diet and a no-fiber control. After two days of acclimatization to the diets, mice were orally inoculated with colitis-associated microbiota. Six mice from each group were sacrificed after two weeks, before the onset of inflammation, and the remaining after eight weeks, during active inflammation. qPCR was used to determine the relative gene expression levels of biomarkers associated with gut barrier function, integrity, and inflammation. SCFAs were quantified using a GC-MS. The DNA from cecal digesta was used for 16S rRNA gene sequencing on a MiniSeq platform.

Results: RMD and ChIn showed intolerance symptoms, including body weight loss, diarrhea, and rectal prolapse, requiring early euthanasia. ChIn increased IL-6 expression and reduced alpha diversity. Conversely, HMP exhibited anti-inflammatory properties, improved colon morphology, enhanced alpha diversity, and decreased IL-6 levels with prolonged exposure. Similarly, WB elevated Occludin and Muc2 expression levels.

Conclusions: The structural complexity of the fiber influenced tolerance and inflammation during dysbiosis. Prolonged exposure to complex fibers like HMP and WB, were well-tolerated, while exposure to less complex fibers like ChIn and RMD aggravated inflammation.

Funding Sources: Whistler Center for Carbohydrate Research and Ralph W. and Grace M. Showalter Research Trust Award.