Exploring the Role of Gut Bacterial Dysbiosis and Gut Inflammation in Fiber Tolerance

Objectives: The prevalence of fiber intolerance has been increasing despite its health benefits. Factors driving this intolerance are still to be determined. Fiber physicochemical properties, gut microbiome heterogeneity and the presence of inflammatory symptoms might contribute to the fiber intolerance. The objective of this study is to evaluate the influence of fiber- and -host-specific conditions in fiber tolerance and metabolism. Methods: Resistant maltodextrins (RMD), high methoxyl pectin (HMP), chicory inulin (ChIn), and wheat bran (WB) were selected based on their physicochemical properties. Six-week-old IL-10 KO germ-free mice were randomly assigned to a purified control diet or 15% fiber-supplemented diet. Mice were colonized using fecal microbiota from a fiber-intolerant individual. Necropsy was then performed after two or eight weeks of treatment. RT-PCR was used to analyze the relative gene expression of cytokines. SCFAs were measured by GC. Bacterial sequencing was done using 16S rRNA sequencing. Results: Within the first two weeks, only RMD increased the expression of IL-6. Short-term consumption of fibers did not increase the production of mucus or short-chain fatty acids (SCFAs). RMD and ChIn reduced the expression of Claudin-1, showing early signs of compromised gut barrier integrity. Eight-week fiber consumption of RMD and ChIn, increased mice colon lengths and IL-6, along with reduced Muc-2 and Claudin-1 expression . Comparison of the two- and eight-week periods, showed exacerbation of inflammation symptoms and gut barrier dysfunction by RMD and ChIn. Despite higher production of SCFAs, adverse effects could not be reversed by RMD or ChIn. HMP treatment showed increased butyrate production and maintained gut barrier integrity. Conclusions: Gut bacterial dysbiosis highly influences fiber metabolism and can lead to inflammation in a fiber- dependent manner regardless of its consumption duration. HMP exerted protective effects against the onset of inflammation symptoms and contributed to a stronger gut barrier integrity. Funding Sources: Whistler Center for Carbohydrate Research and Showalter Research Trust Award.