Dietary resistant starch supplementation increases gut luminal deoxycholic acid abundance in mice

ABSTRACT

Bile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

KEYWORDS:

• Resistant starch
• 7-α-dehydroxylation
• bile acid
• gut microbiome
• DCA
• metagenomics

Acknowledgments

We thank the Biomarkers Core Laboratory at the Columbia University Irving Institute for Clinical and Translational Research (UL1TR001873); the Bioinformatics Core at the UC Davis Genome Center; and the DNA Technologies Core at the UC Davis Genome Center. Research reported in this paper was supported by the NIH National Center for Complimentary and Integrative Health under award number 5R21AT010956-02, T32 GM135741, and T32 ES007059. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCIH, NIEHS, or NIH.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All metagenomics data are available at SRA.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2315632

Additional information

Funding

The work was supported by the National Institutes of Health.