-
1.
Effect of Lactobacillus rhamnosus Probiotic in Early Pregnancy on Plasma Conjugated Bile Acids in a Randomised Controlled Trial.
Chen, Y, Lu, J, Wickens, K, Stanley, T, Maude, R, Stone, P, Barthow, C, Crane, J, Mitchell, EA, Merien, F, et al
Nutrients. 2021;(1)
Abstract
We have previously shown that probiotic supplementation with Lactobacillus rhamnosus HN001 (HN001) led to a reduced incidence of gestational diabetes mellitus (GDM). Here we investigate whether HN001 supplementation resulted in alterations in fasting lipids, insulin resistance, or bile acids (BAs) during pregnancy. Fasting plasma samples collected at 24-30 weeks' gestation, from 348 women randomised at 14-16 weeks' gestation to consume daily probiotic HN001 (n = 172) or a placebo (n = 176) were analysed for lipids, insulin, glucose and BAs. Women supplemented with HN001 had lower fasting glucose compared with placebo (p = 0.040), and lower GDM. Significant differences were found in fasting insulin, HOMA-IR, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein (HDL)-c, triglycerides, total cholesterol, and BAs by GDM status. Lower fasting conjugated BAs were seen in women receiving HN001. A significant decrease of glycocholic acid (GCA) was found in older (age ≥ 35) women who received HN001 (p = 0.005), while GDM women showed significant reduced taurodeoxycholic acid (TDCA) (p = 0.018). Fasting conjugated BA was positively correlated with fasting glucose (r = 0.136, p = 0.020) and fasting insulin (r = 0.113, p = 0.036). Probiotic HN001 supplementation decreases conjugated BAs and might play a role in the improvement of glucose metabolism in women with pregnancy.
-
2.
Preconception insulin resistance and neonatal birth weight in women with obesity: role of bile acids.
Wang, Z, Nagy, RA, Groen, H, Cantineau, AEP, van Oers, AM, van Dammen, L, Wekker, V, Roseboom, TJ, Mol, BWJ, Tietge, UJF, et al
Reproductive biomedicine online. 2021;(5):931-939
Abstract
RESEARCH QUESTION Does maternal preconception insulin resistance affect neonatal birth weight among women with obesity? Is insulin resistance associated with circulating bile acids? Do bile acids influence the association between maternal preconception insulin resistance and neonatal birth weight? DESIGN An exploratory post-hoc analysis of the LIFEstyle randomized controlled trial comparing lifestyle intervention with conventional infertility treatment in women with a BMI of ≥29 kg/m2. Fasting blood samples were collected at randomization and after 3 and 6 months in 469 women. Insulin resistance was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). Bile acid sub-species were determined by liquid chromatography with tandem mass spectrometry. Singletons were included (n = 238). Birth weight Z-scores were adjusted for age, offspring gender and parity. Multilevel analysis and linear regressions were used. RESULTS A total of 913 pairs of simultaneous preconception HOMA-IR (median [Q25; Q75]: 2.96 [2.07; 4.16]) and total bile acid measurements (1.79 [1.10; 2.94]) µmol/l were taken. Preconception HOMA-IR was positively associated with total bile acids (adjusted B 0.15; 95% CI 0.09 to 0.22; P < 0.001) and all bile acid sub-species. At the last measurement before pregnancy, HOMA-IR (2.71 [1.91; 3.74]) was positively related to birth weight Z-score (mean ± SD 0.4 ± 1.1; adjusted B 0.08; 95% CI 0.01 to 0.14; P = 0.03). None of the preconception bile acids measured were associated with birth weight. CONCLUSION Maternal preconception insulin resistance is an important determinant of neonatal birth weight in women with obesity, whereas preconception bile acids are not.
-
3.
Parenteral nutrition impairs plasma bile acid and gut hormone responses to mixed meal testing in lean healthy men.
Meessen, ECE, Bakker, GJ, Nieuwdorp, M, Dallinga-Thie, GM, Kemper, EM, Olde Damink, SW, Romijn, JA, Hartmann, B, Holst, JJ, Knop, FK, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(3):1013-1021
Abstract
BACKGROUND & AIMS To investigate the acute effects of intravenous vs enteral meal administration on circulating bile acid and gut hormone responses. METHODS In a randomized crossover design, we compared the effects of duodenal (via a nasoduodenal tube) vs parenteral (intravenous) administration over 180 min of identical mixed meals on circulating bile acid and gut hormone concentrations in eight healthy lean men. We analysed the bile acid and gut hormone responses in two periods: the intraprandial period from time point (T) 0 until T180 during meal administration and the postprandial period from T180 until T360, after discontinuation of meal administration. RESULTS Intravenous meal administration decreased the intraprandial (AUC (μmol/L∗min) duodenal 1469 ± 284 vs intravenous 240 ± 39, p < 0.01) and postprandial bile acid response (985 ± 240 vs 223 ± 5, p < 0.05) and was accompanied by decreased gut hormone responses including glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, glucagon-like peptide 2 and fibroblast growth factor 19. Furthermore, intravenous meal administration elicited greater glucose concentrations, but similar insulin concentrations compared to enteral administration. CONCLUSIONS Compared to enteral administration, parenteral nutrition results in lower postprandial bile acid and gut hormone responses in healthy lean men. This was accompanied by higher glucose concentrations in the face of similar insulin concentrations exposing a clear incretin effect of enteral mixed meal administration. The alterations in bile acid homeostasis were apparent after only one intravenous meal.
-
4.
Unconjugated and secondary bile acid profiles in response to higher-fat, lower-carbohydrate diet and associated with related gut microbiota: A 6-month randomized controlled-feeding trial.
Wan, Y, Yuan, J, Li, J, Li, H, Zhang, J, Tang, J, Ni, Y, Huang, T, Wang, F, Zhao, F, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(2):395-404
Abstract
BACKGROUND & AIMS Observational studies have shown that diets high in fat and low in dietary fiber, might have an unfavorable impact on bile acid (BA) profiles, which might further affect host cardiometabolic health. In the current study, we aimed to evaluate the effects of dietary fat content on BA profiles and associated gut microbiota, and their correlates with cardiometabolic risk factors. METHODS In a randomized controlled-feeding trial, healthy young adults were assigned to one of the three diets: a lower-fat diet (fat 20%, carbohydrate 66% and protein 14%), a moderate-fat diet (fat 30%, carbohydrate 56% and protein 14%) and a higher-fat diet (fat 40%, carbohydrate 46% and protein 14%) for 6 months. All the foods were provided during the entire intervention period. The BA profiles, associated gut microbiota and markers of cardiometabolic risk factors were determined before and after intervention. RESULTS The higher-fat diet resulted in an elevated concentration of total BAs (p < 0.001), and unconjugated BAs (p = 0.03) compared with lower-fat diet. Secondary BAs, such as deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), 12ketolithocholic acid (12keto-LCA), 3β-DCA and taurolithocholic acid (TLCA) (p < 0.05 after FDR correction) were significantly increased in the higher-fat diet group after the 6-month intervention. Consistently, the abundances of gut bacteria (Bacteroides, Clostridium, Bifidobacterium and Lactobacillus) which affect bile salt hydrolase gene expression were significantly increased after higher-fat consumption. The change of DCA was positively associated with the relative abundance of Bacteroides (r = 0.31, p = 0.08 after FDR correction). In addition, the changes of fecal concentrations of DCA and 12keto-LCA were positively associated with serum total cholesterol (r > 0.3, p = 0.02 and p = 0.008 after FDR correction, respectively). In line with these findings, serum fibroblast growth factor 19 (FGF19) was marginally significantly elevated in the higher-fat group after intervention (p = 0.05). CONCLUSIONS The higher-fat diet resulted in an alteration of BAs, especially unconjugated BAs and secondary BAs, most likely through actions of gut microbiota. These alterations might confer potentially unfavorable impacts on colonic and host cardiometabolic health in healthy young adults. Clinical trial registry number: NCT02355795 listed on NIH website: ClinicalTrials.gov.
-
5.
Bile Acids in Patients with Uncontrolled Type 2 Diabetes Mellitus - The Effect of Two Days of Oatmeal Treatment.
Delgado, GE, Krämer, BK, Scharnagl, H, Fauler, G, Stojakovic, T, März, W, Kleber, ME, Lammert, A
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2020;(9):624-630
Abstract
BACKGROUND Beta-glucans are effective in binding bile acids (BA) thereby lowering cholesterol concentration. This might contribute to the beneficial effects of the consumption of β-glucan-rich foods like oatmeal on glucose homeostasis. OBJECTIVE We measured BA serum concentrations in patients with uncontrolled type 2 diabetes (T2DM) to investigate the effect of two days of oatmeal treatment on BA concentration as compared to a conventional T2DM-adapted diet. METHODS The OatMeal And Insulin Resistance study was performed as a randomized, open label crossover dietary intervention study with consecutive inclusion of 15 patients in an inpatient clinical setting. Bile acids were measured by high-resolution mass spectrometry. For statistical analysis, the differences in the concentration of serum BA and laboratory parameters between the fifth day and the third day of each inpatient stay were calculated and the effect compared between both phases by using the Wilcoxon test. RESULTS Whereas there was a mean decrease in total BA following oatmeal treatment (-0.82±1.14 µmol/l), there was no decrease following the control treatment. Glycocholic acid was lower after oatmeal treatment but higher following control treatment (-0.09±0.17 vs. 0.05±0.11 µmol/l). The reduction in total BA was directly correlated with a decrease in proinsulin during the oatmeal phase. Decreases in blood lipids or apolipoproteins were mostly greater after oatmeal treatment, but these differences were not statistically significant. CONCLUSION Two days of oatmeal diet led to significant reductions in total BA as compared to a diabetes-adapted control diet. The magnitude of BA reduction was directly correlated with a decrease in proinsulin.
-
6.
Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial.
Navarro, SL, Levy, L, Curtis, KR, Elkon, I, Kahsai, OJ, Ammar, HS, Randolph, TW, Hong, NN, Carnevale Neto, F, Raftery, D, et al
Nutrients. 2020;(6)
Abstract
Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20-45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.
-
7.
Postprandial Responses of Serum Bile Acids in Healthy Humans after Ingestion of Turmeric before Medium/High-Fat Breakfasts.
Ghaffarzadegan, T, Zanzer, YC, Östman, E, Hållenius, F, Essén, S, Sandahl, M, Nyman, M
Molecular nutrition & food research. 2019;(21):e1900672
Abstract
SCOPE Bile acids (BAs) are known to regulate a number of metabolic activities in the body. However, very little is known about how BAs are affected by diet. This study aims to investigate whether a single dose of turmeric-based beverage (TUR) before ingestion of medium- (MF) or high-fat (HF) breakfasts would improve the BA profile in healthy subjects. METHODS AND RESULTS Twelve healthy subjects are assigned to a randomized crossover single-blind study. The subjects receive isocaloric MF or HF breakfasts after a drink containing flavored water with or without an extract of turmeric with at least 1-week wash-out period between the treatments. Postprandial BAs are measured using protein precipitation followed by ultra-high-performance liquid chromatography-mass spectrometry analysis. The concentration of BAs is generally higher after HF than MF breakfasts. Ingestion of TUR before MF breakfast increases the serum concentrations of free and conjugated forms of cholic (CA) and ursodeoxycholic acids (UDCA), as well as the concentrations of chenodeoxycholic acid (CDCA) and its taurine-conjugated forms. However, the concentration of conjugated forms of deoxycholic acid (DCA) decreases when TUR is taken before HF breakfast. CONCLUSION TUR ingestion before MF and HF breakfasts improve BA profiles and may therefore have potential health-promoting effects on BA metabolism.
-
8.
Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance.
Weickert, MO, Hattersley, JG, Kyrou, I, Arafat, AM, Rudovich, N, Roden, M, Nowotny, P, von Loeffelholz, C, Matysik, S, Schmitz, G, et al
Nutrition & diabetes. 2018;(1):11
Abstract
Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic-hyperinsulinemic clamps with [6-62H2] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport.
-
9.
Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment.
Gu, Y, Wang, X, Li, J, Zhang, Y, Zhong, H, Liu, R, Zhang, D, Feng, Q, Xie, X, Hong, J, et al
Nature communications. 2017;(1):1785
Abstract
Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.
-
10.
Barley β-glucan reduces blood cholesterol levels via interrupting bile acid metabolism.
Wang, Y, Harding, SV, Thandapilly, SJ, Tosh, SM, Jones, PJH, Ames, NP
The British journal of nutrition. 2017;(10):822-829
Abstract
Underlying mechanisms responsible for the cholesterol-lowering effect of β-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barley β-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7α hydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n 30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barley β-glucan or a control diet, each for 5 weeks. Cholesterol absorption was determined by assessing the enrichment of circulating 13C-cholesterol over 96 h following oral administration; fractional rate of synthesis for cholesterol was assessed by measuring the incorporation rate of 2H derived from deuterium oxide within the body water pool into the erythrocyte cholesterol pool over 24 h; bile acid synthesis was determined by measuring serum 7α-hydroxy-4-cholesten-3-one concentrations. Consumption of 3 g HMW β-glucan decreased total cholesterol (TC) levels (P=0·029), but did not affect cholesterol absorption (P=0·25) or cholesterol synthesis (P=0·14). Increased bile acid synthesis after consumption of 3 g HMW β-glucan was observed in all participants (P=0·049), and more pronounced in individuals carrying homozygous G of rs3808607 (P=0·033). In addition, a linear relationship between log (viscosity) of β-glucan and serum 7α-HC concentration was observed in homozygous G allele carriers. Results indicate that increased bile acid synthesis rather than inhibition of cholesterol absorption or synthesis may be responsible for the cholesterol-lowering effect of barley β-glucan. The pronounced TC reduction in G allele carriers of rs3808607 observed in the previous study may be due to enhanced bile acid synthesis in response to high-viscosity β-glucan consumption in those individuals.