Distinct Postprandial Bile Acids Responses to a High-Calorie Diet in Men Volunteers Underscore Metabolically Healthy and Unhealthy Phenotypes

Abstract

Bile acids (BAs) regulate dietary lipid hydrolysis and absorption in the proximal intestine. Several studies have highlighted a determinant role of circulating levels and/or metabolism of BAs in the pathogenesis of major cardiometabolic diseases. Whether changes in BA profiles are causative or are consequence of these diseases remains to be determined. Healthy male volunteers (n = 71) underwent a postprandial exploration following consumption of a hypercaloric high fat typical Western meal providing 1200 kcal. We investigated variations of circulating levels of 28 BA species, together with BA synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) over an approximately diurnal 12 h period. Analysis of BA variations during the postprandial time course revealed two major phenotypes with opposite fluctuations, i.e., circulating levels of each individual species of unconjugated BAs were reduced after meal consumption whereas those of tauro- and glyco-conjugated BAs were increased. By an unbiased classification strategy based on absolute postprandial changes in BA species levels, we classified subjects into three distinct clusters; the two extreme clusters being characterized by the smallest absolute changes in either unconjugated-BAs or conjugated-BAs. Finally, we demonstrated that our clustering based on postprandial changes in BA profiles was associated with specific clinical and biochemical features, including postprandial triglyceride levels, BMI or waist circumference. Altogether, our study reveals that postprandial profiles/patterns of BAs in response to a hypercaloric high fat challenge is associated with healthy or unhealthy metabolic phenotypes that may help in the early identification of subjects at risk of developing metabolic disorders.

Circulating bile acids concentration is predictive of coronary artery disease in human

“…The supplementary Figure 4 summarize the main results of this work. It proposes a "spill over" mechanism of BA: in the same way of glycemic peak after the meal, this postprandial spillover of BA into the general circulation, has been proposed as an important metabolic factor to take into consideration 16 , 49 .…”

“…To estimate the liver synthesis of BA, we measured the 7a-hydroxy-4-cholesten-3-one (7a-C4) concentrations in serum, the first specific metabolite produced by the liver during hepatic synthesis, the plasma concentration of which reflects the daily rate of bile acid synthesis by the liver in man 24 . The C4 extraction method was similar to the bile acids extraction and the C4 quantification was performed as previously described, using a deuterated C4 form as internal standard (7α-hydroxy-4-cholesten-3-one-d7 49 .…”

The role of the gut microbiota in health and cardiovascular diseases

“…Postprandial BAs profiles are correlated with postprandial lipids, waist circumference, and body mass index (BMI), suggesting that changes in BAs metabolism in response to a high-energy diet may reflect healthy or unhealthy metabolic phenotypes [ 258 ]. In fact, the gut microbiota can regulate glucose metabolism by regulating the interaction between BAs and FXR and TGR5 signaling [ 112 ].…”

Chronic consumption of probiotics, oats, and apples has differential effects on postprandial bile acid profile and cardiometabolic disease risk markers compared with an isocaloric control (cornflakes): a randomized trial

“…Bile acid signaling through the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), can impact the markers of cardiometabolic health by enhancing cholesterol transport in the gut [2] and increasing the release of incretin hormones [3]. The circulating bile acid concentration and profile have been altered postprandially and is dependent on the food component studied and individual health status [4,5]. A positive correlation was shown between postprandial taurine or glycine-conjugated CA and CDCA as well as postprandial triacylglycerol (TAG) [4,6,7].…”

“…The circulating bile acid concentration and profile have been altered postprandially and is dependent on the food component studied and individual health status [4,5]. A positive correlation was shown between postprandial taurine or glycine-conjugated CA and CDCA as well as postprandial triacylglycerol (TAG) [4,6,7]. Therefore, postmeal bile acid responses may be related to metabolic phenotype, and are the potential biomarkers of cardiometabolic disease risk [4].…”