Plain language summary
Bile acids are produced in the liver and are important for the absorption of fat and fat-soluble vitamins. About 95% of bile acids are reabsorbed. Circulating plasma bile acids can affect glucose metabolism and inflammation, and are thought to play a role in the development of metabolic syndrome. The aim of this study was to evaluate how plasma bile acid levels are influenced by a diet rich in whole grains, legumes, fruit and vegetables (low glycaemic load, GL) compared to a diet high in refined grains and sugar (high GL). The study evaluated data from a previous double-blind randomised, cross over feeding trial. 80 healthy adults had the low or high GL diet for four weeks, and after a four-week washout period, received the other diet for four weeks. Three specific plasma bile acids, which are thought to have a positive impact on glucose metabolism, were higher in the low GL group compared to the high GL group. Some individual plasma bile acids were positively associated with HOMA-IR (a measure of glucose metabolism/insulin resistance). There was no significant association between bile acid concentrations and C-reactive protein (a marker of inflammation). The authors conclude that the increase in certain bile acids on the low GL diet may be beneficial and that this effect may be to some extent mediated by the impact of the higher fibre content of the low GL diet on the gut microbial metabolism, which affects plasma bile acid levels.
Abstract
OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied. MATERIALS AND METHODS We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18.5-25.0 kg/m2) and half overweight to obese (BMI 28.0-39.9 kg/m2). Participants consumed two four-week controlled diets in randomized order: 1) a whole grain diet (WG diet), designed to be low in glycemic load (GL), high in whole grains, legumes, and fruits and vegetables, and 2) a refined grain diet (RG diet), designed to be high GL, high in refined grains and added sugars, separated by a four-week washout period. Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography tandem mass spectrometry. Concentrations of glucose, insulin, and CRP were measured in fasting serum. Linear mixed models were used to test the effects of diet on bile acid concentrations, and determine the association between plasma bile acid concentrations and HOMA-IR and CRP. Benjamini-Hochberg false discovery rate (FDR) < 0.05 was used to control for multiple testing. RESULTS A total of 29 plasma bile acids were reliably detected and retained for analysis. Taurolithocholic acid (TLCA), taurocholic acid (TCA) and glycocholic acid (GCA) were statistically significantly higher after the WG compared to the RG diet (FDR < 0.05). There were no significant differences by BMI or sex. When evaluating the association of bile acids and HOMA-IR, GCA, taurochenodeoxycholic acid, ursodeoxycholic acid (UDCA), 5β‑cholanic acid‑3β,12α‑diol, 5‑cholanic acid‑3β‑ol, and glycodeoxycholic acid (GDCA) were statistically significantly positively associated with HOMA-IR individually, and as a group, total, 12α‑hydroxylated, primary and secondary bile acids were also significant (FDR < 0.05). When stratifying by BMI, chenodeoxycholic acid (CDCA), cholic acid (CA), UDCA, 5β-cholanic acid-3β, deoxycholic acid, and total, 12α-hydroxylated, primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals (FDR < 0.05). When stratifying by sex, GCA, CDCA, TCA, CA, UDCA, GDCA, glycolithocholic acid (GLCA), total, primary, 12α‑hydroxylated, and glycine-conjugated bile acids were significantly associated with HOMA-IR among women, and CDCA, GDCA, and GLCA were significantly associated among men (FDR < 0.05). There were no significant associations between bile acids and CRP. CONCLUSIONS Diets with comparable macronutrient and energy composition, but differing in carbohydrate source, affected fasting plasma bile acids differently. Specifically, a diet characterized by whole grains, legumes, and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA, TCA and GCA, ligands for FXR and TGR5, which may have beneficial effects on glucose homeostasis.
