Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species

Abstract

<p>Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (<i>P</i> = 4.1e-03, <i>P</i> = 1.9e-05, respectively), waist circumference (<i>P</i> = 0.017, <i>P</i> = 1.1e-04, respectively), body fat percentage (<i>P</i> = 2.5e-03, <i>P</i> = 2.3e-06, respectively), insulin resistance (<i>P</i> = 0.051, <i>P</i> = 4.6e-4, respectively), fasting concentrations of triglycerides (<i>P</i> = 0.06, <i>P</i> = 9.2e-4, respectively) and leptin (<i>P</i> = 0.067, <i>P</i> = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of <i>Clostridia</i> species (<i>P</i> = 0.037, <i>P</i> = 0.013, <i>P</i> = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of <i>Clostridia</i> species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.<br></p>