Role of de novo syntheses of cholesterol and bile acids in liver, gallbladder emptying, and intestinal transit time in supersaturated bile formation in cholesterol gallstone disease

1994 ◽  
Vol 1 ◽  
pp. 169
Author(s):  
J. Shoda ◽  
B. He ◽  
T. Yoshida ◽  
N. Tanaka ◽  
Y. Matsuzaki ◽  
...  
Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 502-512 ◽  
Author(s):  
Pieter de Groot ◽  
Torsten Scheithauer ◽  
Guido J Bakker ◽  
Andrei Prodan ◽  
Evgeni Levin ◽  
...  

ObjectiveBariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.DesignSubjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.ResultsWe observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.ConclusionAllogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.Trial registration numberNTR4327.


2003 ◽  
Vol 90 (4) ◽  
pp. 803-807 ◽  
Author(s):  
Gene A. Spiller ◽  
Jon A. Story ◽  
Emily J. Furumoto ◽  
Jo Carol Chezem ◽  
Monica Spiller

Sun-dried raisins are a source of dietary fibre and tartaric acid. The effects of tartaric acid on colon function have not been the focus of extensive research. The purpose of the present study was to evaluate the effects of dietary fibre and tartaric acid from sun-dried raisins on colon function and on faecal bile acid and short-chain fatty acid (SCFA) excretion in healthy adults. Thirteen healthy subjects were fed 120 g sun-dried raisins/d or 5 g cream of tartar (equivalent to the tartaric acid in 120 g sun-dried raisins)/d for 9 weeks, divided into 3-week cycles. The experimental diets were fed in a crossover design after an initial control period. Faeces were collected for the last 4 d of each cycle for analysis of SCFA and bile acids. Intestinal transit time decreased from 42h on the baseline diet to 31h on cream of tartar (P<0·1) and to 28h on sun-dried raisins (P<0·05). Faeces were softer on both sun-dried raisins and cream of tartar, but sun-dried raisins increased faecal wet weight (P<0·05), while cream of tartar did not. Sun-dried raisins caused significant reductions from baseline values in total bile acid concentration (from 1·42 (sd 1·03) to 1·09 (sd 0·76) mg/g, P<0·05), whereas cream of tartar did not (1·40 (sd 1·06) mg/g). Sun-dried raisins also significantly reduced the lithocholic (LC):deoxylithocholic acid (DC) ratio (from 1·63 (sd 0·85) to 1·09 (sd 0·50), P<0·02), whereas cream of tartar reduced the ratio, but to a lesser extent (1·29 (sd 0·79), NS). Both faecal bile acids and the LC:DC ratio are indicators of reduced risk for colon cancer. Sun-dried raisins increased total SCFA excretion (from 5·6 (sd 3·4) to 7·6 (sd 3·0) g/4d, P<0·05), which remained unchanged with cream of tartar (5·6 (sd 3·0) g/4d). Both sun-dried raisins and cream of tartar appear to be good stool softeners and to shorten intestinal transit time, although the fibre in sun-dried raisins has the added benefit of increasing faecal weight. Both sun-dried raisins and cream of tartar modulate the composition of faecal bile acids and SCFA in a way that has potential health benefits.


2020 ◽  
Vol 46 (1) ◽  
pp. 83-88
Author(s):  
N. B. Gubergrits ◽  
N.V. Byelyayeva ◽  
T. L. Mozhyna ◽  
G. M. Lukashevich ◽  
P. G. Fomenko

After the discovery of the method of ursodeoxycholic acid’s (UDCA) synthesis and the publication of evidence confirming its ability to reduce the lithogenic properties of bile, active clinical use of UDCA began in the world. This drug, which has pleiotropic effect (choleretic, cytoprotective, immunomodulatory, antiapoptic, litholytic, hypocholesterolemic), has proven its effectiveness in the treatment various diseases: primary biliary cholangitis, intrahepatic cholestasis of pregnancy, gallstone disease. Being a tertiary bile acid, UDCA stimulates bile acid synthesis by reducing the circulating fibroblast growth factor 19 and inhibiting the activation of the farnesoid X-receptor (FXR), which leads to the induction of cholesterol-7α-hydroxylase, a key enzyme in the synthesis of bile acid de novo, mediating the conversion of cholesterol into bile acids. Changes in the formation of bile acids and cholesterol while taking UDCA intake is accompanied by activation of the main enzyme of cholesterol synthesis - 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under the influence of UDCA the activity of stearoyl-Coa desaturase (SCD) in visceral white adipose tissue increases. According to studies conducted in 2019, UDCA improves lipid metabolism by regulating the activity of the ACT/mTOR signaling pathway, reduces the synthesis of cholesterol, decreases the fractional synthesis rate of cholesterol and the fractional synthesis rate of triglycerides. It has been proved that UDCA is accompanied by a decrease in the level of total cholesterol and low density lipoprotein cholesterol.


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