The gut microbiome plays an important role in the regulation of metabolic health, largely through the metabolites it produces, making it an important target for management and prevention of diabetes. Some of the most abundant metabolites produced by the gut microbiome are bile acids. Primary bile acids produced in the liver are converted into secondary bile acids by bacteria in the gut via 7-ɑ-dehydroxylation. These secondary bile acids are strong ligands for bile acid receptors known to improve glycemic regulation. However, the bacteria and enzymatic pathways involved in 7-ɑ-dehydroxylation have not been fully defined. Therefore, we are developing tools with which to study the dynamic regulation of gut bacterial 7-ɑ-dehydroxylation. In this study, we hypothesized that feeding mice a diet rich in resistant starch (RS) would alter the gut microbiome to favor bacteria capable of executing 7-ɑ-dehydroxylation. To test this, mice were fed a diet supplemented with RS or an isocaloric (IC) control diet. Profiling of gut luminal bile acids shows that RS supplementation proportionally increases the production of the secondary bile acid, deoxycholic acid (DCA) (DCA as a proportion of total bile acids in gut luminal contents: IC = 0.16 ± 0.03 RS = 0.55 ± 0.08, P = 0.001). RS tended to decrease unconjugated cholic acid (CA) concentrations, the substrate for 7-ɑ-dehydroxylation in DCA production, compared to IC-fed controls. Hepatic expression of the enzyme required for production of CA, Cyp8b1, did not differ between groups. Therefore, these data suggest that RS-induced increases in DCA are due to increased gut bacterial conversion of CA to DCA. Determining which bacteria can carry out 7-ɑ-dehydroxylation is critical to targeting gut bacterial bile acid metabolism. This study demonstrates that RS supplementation upregulates DCA production, identifying RS supplementation as a tool with which to define the dynamic regulation of 7-ɑ-dehydroxylation by gut bacteria.


M. Reuter: None. M. Tucker: None. Z. Marfori: None. R. Shishani: None. J. M. Bustamante: None. R. Moreno: None. B. Cummings: None.

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