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Changes in fasting bile acid profiles after Roux-en-Y gastric bypass and sleeve gastrectomy.
Zhang, C, Zhang, J, Zhou, Z
Medicine. 2021;(3):e23939
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Abstract
BACKGROUND Bile acid is an essential factor that plays a role in metabolic regulation, but how bile acid is regulated after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remains unclear. This meta-analysis aimed to investigate changes in the levels of fasting bile acids following RYGB and SG. METHODS A systematic literature search of the PubMed, EMBASE, Cochrane Library and Web of Science databases through July 2020 was performed in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The concentrations of bile acids were evaluated. RESULTS Thirteen studies with 289 patients were included. Our results showed that patients who underwent RYGB had increased levels of fasting total bile acids, primary bile acids, secondary bile acids, conjugated bile acids, and unconjugated bile acids, but no significant differences in all these bile acid levels were observed in patients who underwent SG. Furthermore, 12a-hydroxylated bile acid levels and the 12a-hydroxylated/non-12a-hydroxylated bile acid ratio also increased following RYGB. CONCLUSION In this study, we found that fasting bile acid levels, especially 12a-hydroxylated bile acids levels, were increased after RYGB. However, no differences in fasting bile acid levels were observed following SG.
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Targeting bile acid metabolism in obesity reduction: A systematic review and meta-analysis.
So, SSY, Yeung, CHC, Schooling, CM, El-Nezami, H
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2020;(7):e13017
Abstract
A systematic review and meta-analysis was conducted of studies that address the association of bile acid (BA) with obesity and of studies on the effects of treatment in patients with obesity on BA metabolism, assessed from systemic BA, fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4) level, and faecal BA. We searched PubMed, Embase, and the Cochrane Library from inception to 1 August 2019 using the keywords obesity, obese, body mass index, and overweight with bile acid, FGF19, FXR, and TGR5. Two reviewers independently searched, selected, and assessed the quality of studies. Data were analysed using either fixed or random effect models with inverse variance weighting. Of 3771 articles, 33 papers were relevant for the association of BA with obesity of which 22 were included in the meta-analysis, and 50 papers were relevant for the effect of obesity interventions on BA of which 20 were included in the meta-analysis. Circulating fasting total BA was not associated with obesity. FGF19 was inversely and faecal BA excretion was positively associated with obesity. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) modulated BA metabolism, ie, increased BA and FGF19. Our results indicate that BA metabolism is altered in obesity. Certain bariatric surgeries including RYGB and SG modulate BA, whether these underlie the beneficial effect of the treatment should be investigated.
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Biomarkers for bile acid diarrhoea in functional bowel disorder with diarrhoea: a systematic review and meta-analysis.
Valentin, N, Camilleri, M, Altayar, O, Vijayvargiya, P, Acosta, A, Nelson, AD, Murad, MH
Gut. 2016;(12):1951-1959
Abstract
UNLABELLED There is no universally available laboratory test to diagnose bile acid diarrhoea (BAD). OBJECTIVE To conduct a systematic review and meta-analysis to identify a biomarker for idiopathic BAD in patients with functional bowel disorder (FBD) with diarrhoea. DESIGN We searched multiple databases through 15 May 2015. Data were only available to estimate the diagnostic yield of each test (the prevalence of a positive test). Estimates were pooled across studies using the random effects model. RESULTS We included 36 studies, enrolling 5028 patients (24 using 75selenium homotaurocholic acid test (75SeHCAT) retention of <10%, 6 using fasting serum C4, 3 using fasting serum fibroblast growth factor 19 (FGF19) and 2 based on total faecal bile acid (BA) excretion over 48 h). The diagnostic yields (and 95% CI) of abnormal tests were: 0.308 (0.247 to 0.377) for 75SeHCAT retention (<10%), 0.171 (0.134 to 0.217) for serum C4, 0.248 (0.147 to 0.385) for serum FGF19 and 0.255 (0.071 to 0.606) for total faecal BA excretion over 48 h. The majority of the analyses were associated with substantial heterogeneity. Performance characteristics relative to a gold standard test could not be estimated. CONCLUSIONS Overall, the test with the highest diagnostic yield conducted in the largest number of studies was 75SeHCAT retention, which is not widely available in many countries outside Europe and Canada. Using different diagnostic tests, 25% (average) of patients with lower FBD with diarrhoea has evidence of idiopathic BAD. These tests serve to identify idiopathic BAD among patients with FBD with diarrhoea. Further studies are required to appraise the performance characteristics of tests for idiopathic BAD.
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Effect of Bile Acid Sequestrants on the Risk of Cardiovascular Events: A Mendelian Randomization Analysis.
Ross, S, D'Mello, M, Anand, SS, Eikelboom, J, , , Stewart, AF, Samani, NJ, Roberts, R, Paré, G
Circulation. Cardiovascular genetics. 2015;(4):618-27
Abstract
BACKGROUND Statins lower low-density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD), but they may be ineffective or not tolerated. Bile acid sequestrants (BAS) reduce LDL-C, yet their clinical efficacy on CAD remains controversial. METHODS AND RESULTS We conducted a systematic review and meta-analysis of randomized controlled trials to assess the effect of cholestyramine and colesevelam. We then used Mendelian randomization to estimate the effect of BAS on reducing the risk of CAD. First, we quantified the effect of rs4299376 (ABCG5/ABCG8), which affects the intestinal cholesterol absorption pathway targeted by BAS and then we used these estimates to predict the effect of BAS on CAD. Nineteen randomized controlled trials with a total of 7021 study participants were included. Cholestyramine 24 g/d was associated with a reduction in LDL-C of 23.5 mg/dL (95% confidence interval [CI] -26.8,-20.2; N=3806) and a trend toward reduced risk of CAD (odds ratio 0.81, 95% CI 0.70-1.02; P=0.07; N=3806), whereas colesevelam 3.75 g/d was associated with a reduction in LDL-C of 22.7 mg/dL (95% CI -28.3, -17.2; N=759). Based on the findings that rs4299376 was associated with a 2.75 mg/dL decrease in LDL-C and a 5% decrease in risk of CAD outcomes, we estimated that cholestyramine was associated with an odds ratio for CAD of 0.63 (95% CI 0.52-0.77; P=6.3×10(-6)) and colesevelam with an odds ratio of 0.64 (95% CI 0.52-0.79, P=4.3×10(-5)), which were not statistically different from BAS clinical trials (P>0.05). CONCLUSIONS The cholesterol lowering effect of BAS may translate into a clinically relevant reduction in CAD.
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Low nucleotide variability of CYP51A1 in humans: meta-analysis of cholesterol and bile acid synthesis and xenobiotic metabolism pathways.
Lewiñska, M, Zmrzljak, UP, Rozman, D
Acta chimica Slovenica. 2013;(4):875-83
Abstract
Lanosterol 14a-demethylase CYP51 is the most conserved cytochrome P450 (CYP) and is a part of hepatic cholesterol synthesis. Other liver CYPs contribute to cholesterol detoxification through bile acids or to xenobiotic detoxification (DM). To get novel insights into characteristics of the CYP51A1 locus that was so far not linked to human disorders we performed a meta-analysis of CYP51A1 gene polymorphisms in comparison to other liver CYPs and other genes of cholesterol synthesis. Cholesterol linked genes are generally less polymorphic than DM CYPs, with less coding variants, indicating differences in selection pressure between cholesterol and xenobiotic pathways. Among the studied liver CYPs, CYP51A1 has the lowest number of coding variants, and less common variants compared to average for cholesterol synthesis. We were not able to detect other functional molecules within the CYP51 gene (such as lincRNA or miRNA), so we looked into the entire gene locus. We found the AL133568 sequence that overlaps with the CYP51A1 promoter region. Our hypothesis was that the AL133568 transcript may have a role in regulating CYP51A1 expression, but we were unable to prove this experimentally. The reason for the low population variability of the human CYP51A1 thus remains uncertain.