Altered Circulating Bile Acid Composition After Cross-Linked Resistant Starch Consumption

OBJECTIVES: Recent studies have shown potential mechanisms underlying the role of bile acid (BA)-gut microbiota axis in human health and diseases. We and others have shown that resistant starch type 4 (RS4) intake modulates gut microbiota and a range of immunometabolic outcomes in humans and mice. Using available samples (#NCT01887964), we retrospectively examined the hitherto unknown effects of RS4-intake on human plasma BA. METHODS: In a placebo-controlled, two-arm crossover trial, 14 adults with metabolic syndrome consumed control and RS4 supplemented (30% v/v in wheat flour) diets, each for 12 weeks separated by a 2-week washout. Stealth organoleptic properties of RS4 allowed double-blinding. Overnight-fasted samples were collected before and after each diet phase. LC/MS with isotope-labeled internal standards and 16S-rDNA sequencing were used for targeted metabolite and microbiome measurements, respectively. Univariate and multivariate data were analyzed with supervised and unsupervised machine learning algorithms in R-platform. RESULTS: Differences in food ingredients, meal preparations, macronutrients, and energy intakes were minimal among participants due to following communal kitchen and dining practices (p > 0.05). Being a prebiotic fiber, RS4 increased fiber consumption by 1.5-fold (p < 0.001). Taurocholic acid, glycochenodeoxycholic acid, deoxycholic acid, and glycodeoxycholic acid increased in the RS4 group by 92%, 58%, 77%, and 79% respectively (all, p < 0.05) and enriched species of Bacteroides, Bifidobacteria, Roseburia, Eubacterium, Ruminococcus, and Blautia. Members of these genuses are known to have high bile salt hydrolase activity, an enzyme proposed to have a cholesterol-lowering effect. One such species, Bifidobacterium adolescentis showed RS4 specific association with deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid (all, rho >0.50, p < 0.05). Interestingly, the parent study reported significant cholesterol-lowering effects of RS4. CONCLUSIONS: RS4-enriched diet increased fiber consumption and resulted in altered microbiota-dependent secondary BA pool size and composition. Future research may help advance the understanding of the role of prebiotic fibers in BA-microbiota interactions. FUNDING SOURCES: National Institute of Food and Agriculture.