“…In total, three studies assessed the association of fasting 7α‐hydroxy‐4‐cholesten‐3‐one (C4) with obesity, of which two showed higher C4 level associated with obesity 23,28 while the other study 42 had directionally similar estimates that were not statistically significant. However, meta‐analysis was not reported for C4 because one of the studies 28 had an extremely small variance, which contributed most of the weight to the estimate.…”
Section: Resultsmentioning
confidence: 99%
“…LCD does not appear to affect BA metabolism, as reflected by the consistently unchanged FGF19. Conversely, Straniero et al reported VLCD reduced BAs and C4 acutely, 23 suggesting inhibition of BA synthesis. Evidence is still limited, and the effect of LCD on BA remains unclear.…”
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.
“…In total, three studies assessed the association of fasting 7α‐hydroxy‐4‐cholesten‐3‐one (C4) with obesity, of which two showed higher C4 level associated with obesity 23,28 while the other study 42 had directionally similar estimates that were not statistically significant. However, meta‐analysis was not reported for C4 because one of the studies 28 had an extremely small variance, which contributed most of the weight to the estimate.…”
Section: Resultsmentioning
confidence: 99%
“…LCD does not appear to affect BA metabolism, as reflected by the consistently unchanged FGF19. Conversely, Straniero et al reported VLCD reduced BAs and C4 acutely, 23 suggesting inhibition of BA synthesis. Evidence is still limited, and the effect of LCD on BA remains unclear.…”
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.
“…Although firm conclusions about causal relationships should not be purely based on observed correlations, the intestinal microbiota is thus a plausible candidate that may explain observed differences in bile acid levels across the diet groups. Another explanation for the lowered bile acid levels in the colonic luminal content of mice on CR is based on previous observations that faecal excretion of bile acids is reduced upon CR in obese individuals, which is presumably due to a lowered food mass in the colon [72] or due to more efficient uptake in the ileum [73]. In our study, levels of SCFAs in the colonic luminal content were relatively low, which could be inherent to our semi-synthetic diets low in dietary fibre as compared to regular chow diets.…”
Diminished colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an effective strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here, we report the effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice. Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was associated with attenuated immune- and inflammation-related gene expression in the colon. Furthermore, expression of genes involved in lipid metabolism was higher upon CR, which may point towards efficient regulation of energy metabolism. The relative abundance of bacteria considered beneficial to colonic health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed to CR for 28 months as compared to the other diet groups. We found lower plasma levels of interleukin-6 and lower levels of various metabolites, among which are bile acids, in the colonic luminal content of CR-exposed mice as compared to the other diet groups. Switching from CR to an ad libitum moderate-fat diet at old age (24 months) revealed remarkable phenotypic plasticity in terms of gene expression, microbiota composition and metabolite levels, although expression of a subset of genes remained CR-associated. This study demonstrated in a comprehensive way that CR affects indicators of colonic health in aging mice. Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, which may contribute to healthy aging.
“…Bile-acidactivated signaling pathways have become attractive therapeutic targets for metabolic disorders, such as obesity, type 2 diabetes, hypertriglyceridemia, and atherosclerosis, as well as other associated chronic diseases, such as nonalcoholic steatohepatitis [82,83]. The results have shown that a 40% CR increased the BA pool size (162%) and total BAs in gallbladder, small intestinal contents, and serum, with contributions mainly from taurocholic acid (TCA) and some secondary BAs, such as taurodeoxycholic acid, deoxycholic acid, lithocholic acid (LCA), w-muricholic acid, and hyodeoxycholic acid [84][85][86]. Increases in these CR-induced BAs might be due to an increase in the rate of BA synthesis, conjugation in liver and intracellular transport in the ileum.…”
Calorie restriction (CR) is a dietary regimen that reduces calorie intake without incurring malnutrition or a reduction in essential nutrients. It has long been recognized as a natural strategy for promoting health, extending longevity, and prevents the development of metabolic and age-related diseases. In the present review, we focus on the general effect of CR on gut microbiota composition and global metabolism. We also propose mechanisms for its beneficial effect. Results showed that probiotic and butyrate-producing microbes increased their relative abundance, whereas proinflammatory strains exhibited suppressed relative abundance following CR. Analyses of the gut microbial and host metabolisms revealed that most host microbial co-metabolites were changed due to CR. Examples of dramatic CR-induced changes in host metabolism included a decrease in the rate of lipid biosynthesis and an increase in the rates of fatty acid catabolism, β-oxidation, glycogenolysis, and gluconeogenesis. The observed phenotypes and the further verification of the direct link between gut microbiota and metabolome may benefit patients that are at risk for developing metabolic disease. Thus, improved gut microbiota composition and metabolome are potential biomarkers for determining the effectiveness of dietary interventions for age-related and metabolic diseases.
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