Relative strength of non-digestible carbohydrates in stimulating butyrate production and modifying experimental colitis symptoms in mouse models

Butyrate deficiency has important implications in physiology and disease. Using dietary interventions to overcome butyrate insufficiency has been attempted for decades. Dozens of dietary fibers (DF) rich in non-digestible carbohydrates (NDC) possess butyrogenic properties. However, their relative strength in stimulating butyrate production has yet to be systematically compared in vivo . Here we evaluated the butyrogenic properties of nine widely used NDC in modifying colitic symptoms in mice. We ranked their relative strength in stimulating butyrate production under both healthy and colitic conditions. Our longitudinal data modelled trajectories of each NDC tested in promoting butyrate production under both health conditions. Our data demonstrated that NDC supplementation resulted in 1.69 times higher butyrate in healthy than colitic mice ( P = 7.49×10 −4 ), underscoring the importance of health status-dependent selection of optimal NDC in designing clinical trials. The mice supplemented with fructooligosaccharides (FOS), and β-glucan, resistant starch 3 (RS3) had the highest butyrogenic strength at 157.11%, 154.07%, and 152.42%, respectively, compared to the mice fed the basal diet (100%). These DF modified colitic phenotypes, including reducing serum LPS concentrations and repressing intestinal inflammation. The ability of these NDC in modulating gut microbiota varies substantially, depending on interactions between specific DF types and host health status. The full-length 16S rRNA gene sequencing-based approach used allowed us to identify microbiota features at species and strain levels and to detect strong correlations between species abundance and short-chain fatty acid concentrations. Our results provide mechanistic bases for precise modulation of gut microbiota using NDC. Our findings on health status-dependent butyrogenic efficacy are of pragmatic value in designing intervention studies and recruiting volunteers in clinical trials for overcoming butyrate deficiency. Formulations of optimal NDC mixtures targeting specific butyrate biosynthesis pathways without having a broad impact on native gut microbiota can be advantageous in microbial ecology engineering.