Abstract/Summary

Age-related diseases, including Type 2 diabetes mellitus and metabolic syndrome are a pressing global health challenge that is expected to rise. They are associated with the composition of the gut microbiome, which has roles in metabolism, inflammation, and the immune system. Recent research has unveiled that bile acids, in addition to their well-established roles in maintaining metabolic homeostasis, can significantly impact the composition and function of the gut microbiome and hold potential as therapeutic agents that can promote the growth of beneficial gut bacteria, thereby conferring health benefits. Using batch culture in vitro fermentation models, several bile acids were screened for their effects on beneficial bacterial species and corresponding short chain fatty acids (SCFAs). From the bile acids screened, 7-KLCA, UDCA and UCA were found to increase the numbers of probiotic bacterial groups, with subsequent three-stage continuous culture fermentations demonstrating the differing effects of these bile acids on the gut microbiota. 7-KLCA was found to promote the growth of important butyrate-producing bacterial species, including Faecalibacterium prausnitzii, Eubacterium rectale, and Roseburia species. Bile acid profiling results elucidated to the rapid metabolism of 7-KLCA to UDCA by bacterial species with cell culture studies suggesting that bile acid treatment can lead to expression changes in genes associated with a healthier metabolic phenotype. Taken collectively, these findings suggest that 7-KLCA may exert therapeutic effects with the potential to modulate gut microbiota, promote the production of health-promoting SCFAs and regulate gene expression. They highlight its promise as a novel agent in the prevention, as a nutraceutical supplement, and even as a possible therapeutic agent, in the treatment of metabolic diseases, including prediabetes and T2DM.