title: The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: a randomized controlled trial. Comparison of Changes in Lipid Profile after Bilio-intestinal Bypass and Gastric Banding in Patients with Morbid Obesity Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner GLUCAGON-LIKE PEPTIDE-1 7-36: A PHYSIOLOGICAL INCRETIN IN MAN Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT) inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs. Effect of laparoscopic Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus with hypertension: a randomized controlled trial. Physiological control of cholecystokinin release and pancreatic enzyme secretion by intraduodenal bile acids. Gut Hormones as Mediators of Appetite and Weight Loss After Roux-en-Y Gastric Bypass Diet-induced thermogenesis and respiratory quotient after Roux-en-Y gastric bypass surgery: a prospective study. Lipid profile changes in patients undergoing bariatric surgery: a comparative study between sleeve gastrectomy and mini-gastric bypass. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. Genomic analysis of hepatic farnesoid X receptor binding sites reveals altered binding in obesity and direct gene repression by farnesoid X receptor in mice. Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes. Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 5‐Year Outcomes Microbial ecology: Human gut microbes associated with obesity Dietary intervention impact on gut microbial gene richness Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids.
abstract: Gastric bypass leads to the remission of  type 2 diabetes  independently of weight loss . Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation . We prospect ively studied 12 patients undergoing gastric bypass and six patients undergoing gastric b and ing over a 6-wk period . Plasma fibroblast growth factor (FGF)19 , stimulated by bile acid absorption in the terminal ileum , and plasma bile acids were measured . In canine and rodent models , we investigated changes in the gut hormone response after altered bile flow . FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric b and ing . In the canine model , both food and bile , on their own , stimulated satiety gut hormone responses . However , when combined , the response was doubled . In rats , drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response , reduced food intake , and lower body weight . In conclusion , after gastric bypass , bile flow is altered , leading to increased plasma bile acids , FGF19 , incretin . and satiety gut hormone concentrations . Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes CONTEXT Obstructive sleep apnea ( OSA ) is strongly related to obesity . Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA . OBJECTIVE To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial of 60 obese patients ( body mass index : > 35 and < 55 ) with recently diagnosed ( < 6 months ) OSA and an apnea-hypopnea index ( AHI ) of 20 events/hour or more . These patients had been prescribed continuous positive airway pressure ( CPAP )  therapy to manage OSA and were identified via accredited community sleep clinics . The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical research ers in Melbourne , Australia . Patients with obesity hypoventilation syndrome , previous bariatric surgery , contraindications to bariatric surgery , or significant cardiopulmonary , neurological , vascular , gastrointestinal , or neoplastic disease were excluded . INTERVENTIONS Patients were r and omized to a conventional weight loss program that included regular consultations with a dietitian and physician , and the use of very low-calorie diets as necessary ( n = 30 ) or to bariatric surgery ( laparoscopic adjustable gastric b and ing ; n = 30 ) . MAIN OUTCOME MEASURES The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to r and omization . Secondary outcomes were changes in weight , CPAP adherence , and functional status . RESULTS Patients lost a mean of 5.1 kg ( 95 % CI , 0.8 to 9.3 kg ) in the conventional weight loss program compared with 27.8 kg ( 95 % CI , 20.9 to 34.7 kg ) in the bariatric surgery group ( P < .001 ) . The AHI decreased by 14.0 events/hour ( 95 % CI , 3.3 to 24.6 events/hour ) in the conventional weight loss group and by 25.5 events/hour ( 95 % CI , 14.2 to 36.7 events/hour ) in the bariatric surgery group . The between-group difference was -11.5 events/hour ( 95 % CI , -28.3 to 5.3 events/hour ; P = .18 ) . CPAP adherence did not differ between the groups . The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score ( mean , 9.3 [ 95 % CI , 0.5 to 18.0 ] ; P = .04 ) . CONCLUSION Among a group of obese patients with OSA , the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss . TRIAL REGISTRATION anzctr.org Identifier : 12605000161628 Background : The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery . Methods : We prospect ively investigated the effects of the bilio-intestinal bypass ( BI-bypass ) with a wide cholecysto-jejunal anastomosis and of adjustable gastric b and ing ( AGB ) on blood lipid concentrations in obese patients . To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass , daily fecal sterol excretion was measured by gas-liquid chromatography ( GLC ) . Results : At 1 year after BI-bypass compared to baseline , the hypercholesterolemic ( n=18 ) and the normocholesterolemic ( n=19 ) patients significantly reduced total ( −38 % and −27 % , respectively ) , LDL ( −47 % and −24 % , respectively ) and HDL ( −11 % and −13 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −25 % and −13 % , respectively ) . At 1 year after AGB , the total / HDL cholesterol ratio was significantly decreased ( −11 % ) compared to baseline in hypercholesterolemic ( n=12 ) but not in normocholesterolemic ( n=6 ) patients , while total and LDL cholesterol were not affected in both groups . At 3 years after BI-bypass compared to baseline , the hypercholesterolemic ( n=9 ) and the normocholesterolemic ( n=11 ) patients significantly reduced total ( −43 % and −28 % , respectively ) and LDL ( −53 % and −29 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −38 % and −21 % , respectively ) . The BI-bypass induced a significant ( P < 0.005 ; n=7 ) 6-fold increase in mean fecal cholesterol output . Conclusions : The BI-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output . BI-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia Objective Our objective was to investigate the role of bile acids in  hepatic steatosis reduction after vertical sleeve gastrectomy ( VSG ) . Design and Methods  High fat diet ( HFD ) induced obese C57Bl/6 mice were r and omized to : VSG , Sham operation ( Sham ) , Sham operation with pair feeding to VSG ( Sham-PF ) , or non-surgical controls ( Naïve ) . All mice were on HFD until sacrifice . Mice were observed post-surgery and data for body weight , body composition , metabolic parameters , serum bile acid level and composition were collected . Further hepatic gene expression by RNAseq and RT-PCR analysis was assessed . Results VSG and Sham-PF mice lost equal weight post-surgery while VSG mice had the lowest hepatic triglyceride content at sacrifice . The VSG mice had elevated serum bile acid levels that positively correlated with maximal weight loss . Serum bile composition in the VSG group had increased cholic and tauroursodeoxycholic acid . These bile acid composition changes in VSG mice explained observed downregulation of hepatic lipogenic and bile acid synthetic genes . Conclusion VSG in obese mice results in greater hepatic steatosis reduction than seen with caloric restriction alone . VSG surgery increases serum bile acids that correlate with weight lost post-surgery and changes serum bile composition that could explain suppression of hepatic genes responsible for lipogenesis The physiological role of glucagon-like peptide-1 7 - 36 amide ( GLP-1 7 - 36 ) in man was investigated . GLP-1 7 - 36-like immunoreactivity was found in the human bowel ; its circulating level rose after oral glucose and after a test breakfast . When it was infused into seven volunteers at a rate to mimic its postpr and ial plasma concentration in the fasting state , plasma insulin levels rose significantly and glucose and glucagon concentrations fell . During an intravenous glucose load , it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations , compared with a control saline infusion , even inducing postinfusion reactive hypoglycaemia . By comparison , infusion of glucose-dependent insulinotropic peptide ( GIP ) to physiological levels was less effective in stimulating insulin release . These observations suggest that GLP-1 7 - 36 is a physiological incretin and that it is more powerful than GIP . The observation of greatly increased postpr and ial plasma GLP-1 7 - 36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder OBJECTIVE Increased delivery of bile acid salts ( BA ) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery . To further eluci date a potential role of BA in the secretion of GLP-1 and PYY , we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospect i ve , r and omized 1-year trial . DESIGN AND METHODS Patients  received a st and ard test meal and blood was collected before and after eating , prior to , and 1 week , 3 months , and 12 months after surgery . RESULTS Pre-surgery , basal BA concentrations were significantly lower in bariatric patients than in healthy controls . One year post-surgery , bariatric patients expressed variably increased BA concentrations ( gastric bypass patients ∼2 fold increase , P ≤ 0.05 ) . However , whereas in both patient groups , marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery , changes in plasma BA followed a different pattern : basal and postpr and ial plasma BA concentrations increased much slower , more progressively with significant increases only 1-year post-surgery . CONCLUSIONS Based on these findings , BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome . Changes in intestinal and hepatic physiology after ileal interposition ( transposition ) surgery ( IIS )  are not well understood . Our aim was to eluci date the adaptation of the interposed ileum , which we hypothesized , would lead to early bile acid reabsorption in the interposed ileum , thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments . Rats with diet-induced obesity were r and omized to IIS  , with 10 cm of ileum repositioned distal to the duodenum , or sham surgery . A subgroup of sham rats was pair-fed to IIS rats . Physiological parameters were measured until 6 wk postsurgery . IIS rats ate less and lost more weight for the first 2 wk postsurgery . At study completion , body weights were not different , but IIS rats had reversed components of the metabolic syndrome . The interposed ileal segment adapted to a more jejunum-like villi length , mucosal surface area , and GATA4/ILBP mRNA . The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi . IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum , suggesting an early and efficient reabsorption of primary bile acids . IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss . There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR , SHP , or NTCP expression . IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling . There is early reabsorption of primary bile acids despite selective " jejunization " of the interposed ileal segment . Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery Abstract Objective . Exogenous bile acid ( BA ) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass ( RYGB ) surgery . Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB , with subsequent increased fasting plasma BAs . The study assessed fasting and post-pr and ial plasma BA response before and 15 months after RYGB . Material and methods . The prospect i ve study recruited 63 obese individuals ( 43 females ) , aged 43 ( 36–56 ) [ median ( IQR ) ] years .  Blood sample s were collected before and every 30 min for 120 min after a st and ard 400 kcal meal .  Fasting and post-pr and ial plasma BAs , glucagons like peptide-1 ( GLP-1 ) , –tyrosine ( PYY ) , fasting C-reactive protein ( CRP ) , glucose and insulin were measured and homeostasis model assessment -insulin resistance ( HOMA-IR ) was calculated . Results . Following RYGB , body mass index , CRP , fasting glucose and HOMA-IR decreased ; 43.7 ( 39.3–49.2 ) kg/m2 to 29.2 ( 25.1–35.0 ) kg/m2 , 7.9 ( 4.1–11.9 ) mg/L to 0.4 ( 0.2–1.0 ) mg/L , 5.5 ( 5.0–6.0 ) mmol/L to 4.6 ( 4.3–4.9 ) mmol/L and 5.9 ( 3.5–9.2 ) to 1.7 ( 1.1–2.2 ) , respectively , all P < 0.001 . Fasting total BAs , GLP-1 and PYY increased after RYGB ; 1.69 ( 0.70–2.56 ) µmol/L to 2.43 ( 1.23–3.82 ) µmol/L ( P = 0.02 ) , 6.8 ( 1.5–15.3 ) pmol/L to 17.1 ( 12.6–23.9 ) pmol/L ( P < 0.001 ) and 4.0 ( 1.0–7.1 ) pmol/L to 15.2 ( 10.0–28.3 ) pmol/L ( P < 0.001 ) , respectively . The area under the curve for post-pr and ial total BAs , total glycine-conjugated BAs , GLP-1 and PYY were greater after RYGB ; 486 ( 312–732 ) µmol/L/min versus 1012 ( 684–1921 ) µmol/L/min , 315 ( 221–466 ) µmol/L/min versus 686 ( 424–877 ) µmol/L/min , 3679 ( 3162–4537 ) pmol/L/min versus 5347 ( 4727–5781 ) pmol/L/min and 1887 ( 1423–2092 ) pmol/L/min versus 3296 ( 2534–3834 ) pmol/L/min , respectively , all P < 0.0001 . Conclusion . Weight loss following RYGB is associated with an increase in post-pr and ial plasma BA response due to larger amounts of glycine-conjugated BAs . This suggests up regulation of BA production and conjugation after RYGB Male Hartley guinea pigs were r and omly allocated to one of four treatments , 10 guinea pigs per group , for 12 weeks . The control diet contained no ASBT inhibitor ( ASBTi ) or simvastatin . Low ASBTi ( LowASBTi ) and high ASBTi ( HighASBTi ) were monotherapies containing 0.03 g/100 g and 0.1 g/100 g of the ASBTi SC-435 . Combination therapy ( COMBO ) was a combination therapy consisting of 0.03 g/100 g ASBTi and 0.05 g/100 g simvastatin . Based on food consumption , guinea pigs received 17.2 and 47.8 mg/kg per day ASBTi in the ASBTi groups or 13.7 mg/kg per day ASBTi and 21.4 mg/kg per day simvastatin in the COMBO group . The amount of cholesterol in each diet was 0.25 g/100 g. LDL cholesterol was 40 and 70 % lower with the HighASBTi and COMBO treatments compared to controls . Plasma triglycerides ( TG ) were 70 % lower with COMBO therapy while HDL cholesterol was 43 - 47 % higher with all treatments . Hepatic free cholesterol was reduced 60 - 80 % with all treatments . Cholesterol content in the aortic arch was reduced by 25 and 42 % in the HighASBTi and COMBO groups . Fecal bile acids were increased by 2.5- and 4-fold with HighASBTi and COMBO treatments . These data suggest that the interruption in the enterohepatic circulation of bile acids by ASBTi and statin co-administration therapy cause a significant reduction in plasma cholesterol concentrations and attenuate the progression of atherosclerosis in guinea pigs AIMS The aim of this study was to evaluate the effect of laparoscopic Roux-en-Y gastric bypass ( RYGB ) surgery compared with usual care with and without Exenatide therapy in obese people with type 2 diabetes mellitus ( T2DM ) and hypertension . METHODS 108 obese T2DM with hypertension were enrolled and r and omly allocated to usual care ( group A ) , usual care plus Exenatide ( group B ) , and RYGB surgery ( group C ) . Demographic characteristics , metabolic parameters and cardiac structure/function along with inflammatory cytokines were measured and compared before and after 12 months . RESULTS At 12 months , diabetes remission had occurred in no patients in groups A and B versus 90 % in group C , and there was a significant decrease in requirement of antihypertensive drugs in group C compared with groups A and B ( P<0.05 ) . Other parameters ( body mass index , hemoglobin A1c , homeostasis model assessment of insulin resistance , lipids ) , inflammation index ( high sensitivity C-reactive protein , tumor necrosis factor-α , high molecular weight adiponectin ) and cardiac structure ( left ventricular mass index ) were significantly improved in groups B and C , but patients in group C had the greatest degree of improvement ( P<0.05 ) . CONCLUSION RYGB surgery improves a number of parameters including cardiovascular function in obese hypertensive people with T2DM . This is likely to be due to , at least in part , an improvement in the abnormal metabolic panel and to reduced inflammation BACKGROUND : The physiological relevance of duodenal bile acids in the control of cholecystokinin release and pancreatic enzyme secretion is still unknown . AIMS : To provide a near physiological situation by perfusing a bile acid mixture mimicking the individual endogenous bile acid composition of the person under investigation . For maximal reduction of endogenous bile output the CCK-A receptor antagonist loxiglumide was infused intravenously . SUBJECTS AND METHODS : Seven healthy volunteers were studied on four different days by a duodenal marker perfusion technique . The individual bile acid composition in duodenal juice and test meal stimulated bile acid output was assessed on day 1 . Bile acids were perfused at an amount of 30 or 100 % as determined on day 1 in combination with the test meal in the presence or absence of loxiglumide . Pancreatic enzymes , bilirubin , and bile acid output were determined in duodenal juice . Plasma cholecystokinin ( CCK ) and plasma pancreatic polypeptide ( PP ) were measured radioimmunologically . RESULTS : Bile acid perfusion did not significantly alter stimulated pancreatic enzyme , bilirubin or bile acid output or plasma CCK . Loxiglumide did not alter basal CCK release but increased test meal stimulated CCK output fourfold ( p < 0.05 ) . The addition of bile acids to the test meal at a dose resembling 30 % of bile acid output as determined on day 1 prevented this increase . Plasma PP concentration remained unchanged by bile acids and were mostly undetectable during loxiglumide infusion . CONCLUSIONS : The CCK producing cell is under constant suppression by intraduodenal bile acids which can not be further enhanced by a physiological bile acid mixture . However , removal of duodenal bile acids by inhibition of gall bladder contraction unmasks this suppression leading to a dramatic increase in plasma CCK levels . As little as one third of postpr and ially released bile acids completely reverse this effect . Bile acids are the most important luminal regulator of CCK release in humans Objective : To evaluate the physiologic importance of the satiety gut hormones . Background : Controversy surrounds the physiologic role of gut hormones in the control of appetite . Bariatric surgery remains the most effective treatment option for obesity , and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass . Methods : We correlated peptide YY ( PYY ) and glucagon-like peptide 1 ( GLP-1 ) changes within the first week after gastric bypass with changes in appetite . We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass .  Finally , we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake . Results : Postpr and ial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass ( P < 0.05 ) . Changes in appetite are evident within days after gastric bypass surgery ( P < 0.05 ) , and unlike other operations , the reduced appetite continues . However , in patients with poor weight loss after gastric bypass associated with increased appetite , the postpr and ial PYY and GLP-1 responses are attenuated compared with patients with good weight loss ( P < 0.05 ) . Inhibiting gut hormone responses , including PYY and GLP-1 after gastric bypass , results in return of appetite and increased food intake ( P < 0.05 ) . Conclusion : The attenuated appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations , and appetite returns when the release of gut hormones is inhibited . The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implication s for the treatment of obesity BACKGROUND Studies in humans and other animals have shown that Roux-en-Y gastric bypass ( RYGB ) leads to increased energy expenditure ( EE ) . We analyzed several components of EE , such as the respiratory quotient ( RQ ) , resting metabolic rate ( RMR ) , and diet-induced thermogenesis ( DIT ) among patients before and after RYGB . METHODS In this prospect i ve clinical study , RMR , DIT , and RQ were measured by indirect calorimetry ( IC ) in the same patients before and 12 months after RYGB  ( the preoperative and postoperative time points , respectively ) . Postpr and ial RQ and DIT were measured after patients consumed a st and ard ~270 kcal meal ( 62 % carbohydrates , 12 % proteins , and 26 % lipids ) . RESULTS The population studied consisted of 13 patients ( mean age 40.8 ± 6.7 years , 85 % female).At the postoperative ( postop ) time point , patients showed higher weight-adjusted RMR compared with the preoperative ( preop ) time point ( P<.01 ) . The absolute and weight-adjusted metabolic rates 20 minutes after the meal were increased postoperatively ( P<.0001 ) but not preoperatively ( P = 0.2962 ) ( DIT ) ; this increase in RQ was significantly higher in the postop than in the preop time point . CONCLUSION The observed patients showed increased EE , DIT , and RQ after RYGB surgery . These data may serve as important physiologic factors contributing to the loss and maintenance of weight after RYGB OBJECTIVE To prospect ively evaluate the effect of different types of bariatric surgery on lipid profile . METHODS  Total cholesterol ( TC ) , High-Density-Lipoprotein cholesterol ( HDLc ) , Low-Density-Lipoprotein cholesterol ( LDLc ) and triglycerides ( TG ) levels  were evaluated before surgery and at 3 different post-operative time-points ( 3 , 6 and 12 months ) in consecutive obese subjects undergoing mini-gastric bypass ( MGB ) or sleeve gastrectomy ( SG ) . RESULTS At baseline , 74 MGB and 86 SG subjects were comparable for lipid profile and prevalence of hypercholesterolemia/hypertriglyceridemia . During the post-operative follow-up , both MGB and SG subjects showed significant changes in lipid profile . However , at 3 months , MGB patients showed higher changes in TC ( β = 0.179 , p = 0.022 ) and TG ( β = 0.265 , p = 0.001 ) than those undergoing SG . At 6-month post-operative follow-up , these differences were confirmed only for TC . After a 12-month follow-up , MGB and SG were entirely comparable for changes in lipid profile with the exception of HDLc , whose changes were higher in SG group ( β = 0.130 , p = 0.039 ) . Overall , the probability to normalize lipid profile during the 12-month follow-up was similar in MGB and in SG patients ( OR:1.24 , 95%CI:0.41 - 3.76 , p = 0.689 ) . CONCLUSION Despites some differences at 3 - 6 post-operative months , during a 12-month follow-up , SG and MGB showed a similar efficacy in the improvement of lipid profile of obese patients BACKGROUND & AIMS The 7α-dehydroxylation of primary bile acids ( BAs ) , chenodeoxycholic ( CDCA ) and cholic acid ( CA ) into the secondary BAs , lithocholic ( LCA ) and deoxycholic acid ( DCA ) , is a key function of the gut microbiota . We aim ed at study ing the linkage between fecal BAs and gut microbiota in cirrhosis since this could help underst and cirrhosis progression . METHODS Fecal microbiota were analyzed by culture-independent multitagged-pyrosequencing , fecal BAs using HPLC and serum BAs using LC-MS in controls , early ( Child A ) and advanced cirrhotics ( Child B/C ) . A subgroup of early cirrhotics underwent BA and microbiota analysis before/after eight weeks of rifaximin . RESULTS Cross-sectional : 47 cirrhotics ( 24 advanced ) and 14 controls were included . In feces , advanced cirrhotics had the lowest total , secondary , secondary / primary BA ratios , and the highest primary BAs compared to early cirrhotics and controls . Secondary fecal BAs were detectable in all controls but in a significantly lower proportion of cirrhotics ( p<0.002 ) . Serum primary BAs were higher in advanced cirrhotics compared to the rest . Cirrhotics , compared to controls , had a higher Enterobacteriaceae ( potentially pathogenic ) but lower Lachonospiraceae , Ruminococcaceae and Blautia ( 7α-dehydroxylating bacteria ) abundance . CDCA was positively correlated with Enterobacteriaceae ( r=0.57 , p<0.008 ) while Ruminococcaceae were positively correlated with DCA ( r=0.4 , p<0.05 ) . A positive correlation between Ruminococcaceae and DCA/CA ( r=0.82 , p<0.012 ) and Blautia with LCA/CDCA ( r=0.61 , p<0.03 ) was also seen . Prospect i ve study : post-rifaximin , six early cirrhotics had reduction in Veillonellaceae and in secondary / primary BA ratios . CONCLUSIONS Cirrhosis , especially advanced disease , is associated with a decreased conversion of primary to secondary fecal BAs , which is linked to abundance of key gut microbiome taxa UNLABELLED The nuclear bile acid receptor , farnesoid X receptor ( FXR ) , is an important transcriptional regulator of liver metabolism . Despite recent advances in underst and ing its functions , how FXR regulates genomic targets and whether the transcriptional regulation by FXR is altered in obesity remain largely unknown . Here , we analyzed hepatic genome-wide binding sites of FXR in healthy and dietary obese mice by chromatin immunoprecipitation sequencing ( ChIP-seq ) analysis . A total of 15,263 and 5,272 FXR binding sites were identified in livers of healthy and obese mice , respectively , after a short 1-hour treatment with the  synthetic FXR agonist , GW4064 . Of these sites , 7,440 and 2,344 were detected uniquely in healthy and obese mice .  FXR-binding sites were localized mostly in intergenic and intron regions at an inverted repeat 1 motif in both groups , but also clustered within 1 kilobase of transcription start sites . FXR-binding sites were detected near previously unknown target genes with novel functions , including diverse cellular signaling pathways , apoptosis , autophagy , hypoxia , inflammation , RNA processing , metabolism of amino acids , and transcriptional regulators . Further analyses of r and omly selected genes from both healthy and obese mice suggested that more FXR-binding sites are likely functionally inactive in obesity . Surprisingly , occupancies of FXR , retinoid X receptor alpha , RNA polymerase II , and epigenetic gene activation and repression histone marks , and messenger RNA levels of genes examined , suggested that direct gene repression by agonist-activated FXR is common . CONCLUSION Comparison of genomic FXR-binding sites in healthy and obese mice suggested that FXR transcriptional signaling is altered in dietary obese mice , which may underlie aberrant metabolism and liver function in obesity BACKGROUND In short-term r and omized trials ( duration , 1 to 2 years ) , bariatric surgery has been associated with improvement in type 2 diabetes mellitus . METHODS We assessed outcomes 3 years after the r and omization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy .  The primary end point was a glycated hemoglobin level of 6.0 % or less . RESULTS The mean ( ±SD ) age of the patients at baseline was 48±8 years , 68 % were women , the mean baseline glycated hemoglobin level was 9.3±1.5 % , and the mean baseline body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 36.0±3.5 . A total of 91 % of the patients completed 36 months of follow-up . At 3 years , the criterion for the primary end point was met by 5 % of the patients in the medical-therapy group , as compared with 38 % of those in the gastric-bypass group ( P<0.001 ) and 24 % of those in the sleeve-gastrectomy group ( P=0.01 ) . The use of glucose-lowering medications , including insulin , was lower in the surgical groups than in the medical-therapy group . Patients in the surgical groups had greater mean percentage reductions in weight from baseline , with reductions of 24.5±9.1 % in the gastric-bypass group and 21.1±8.9 % in the sleeve-gastrectomy group , as compared with a reduction of 4.2±8.3 % in the medical-therapy group ( P<0.001 for both comparisons ) . Quality -of-life measures were significantly better in the two surgical groups than in the medical-therapy group . There were no major late surgical complications . CONCLUSIONS Among obese patients with uncontrolled type 2 diabetes , 3 years of intensive medical therapy plus bariatric surgery result ed in glycemic control in significantly more patients than did medical therapy alone . Analyses of secondary end points , including body weight , use of glucose-lowering medications , and quality of life , also showed favorable results at 3 years in the surgical groups , as compared with the group receiving medical therapy alone . ( Funded by Ethicon and others ; STAMPEDE Clinical Trials.gov number , NCT00432809 . ) BACKGROUND Long‐term results from r and omized , controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited . METHODS We assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body‐mass index ( BMI ; the weight in kilograms divided by the square of the height in meters ) of 27 to 43 were r and omly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux‐en‐Y gastric bypass or sleeve gastrectomy . The primary outcome was a glycated hemoglobin level of 6.0 % or less with or without the use of diabetes medications . RESULTS Of the 150 patients who underwent r and omization , 1 patient died during the 5‐year follow‐up period ; 134 of the remaining 149 patients ( 90 % ) completed 5 years of follow‐up . At baseline , the mean ( ±SD ) age of the 134 patients was 49±8 years , 66 % were women , the mean glycated hemoglobin level was 9.2±1.5 % , and the mean BMI was 37±3.5 . At 5 years , the criterion for the primary end point was met by 2 of 38 patients ( 5 % ) who received medical therapy alone , as compared with 14 of 49 patients ( 29 % ) who underwent gastric bypass ( unadjusted P=0.01 , adjusted P=0.03 , P=0.08 in the intention‐to‐treat analysis ) and 11 of 47 patients ( 23 % ) who underwent sleeve gastrectomy ( unadjusted P=0.03 , adjusted P=0.07 , P=0.17 in the intention‐to‐treat analysis ) . Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone ( 2.1 % vs. 0.3 % , P=0.003 ) . At 5 years , changes from baseline observed in the gastric‐bypass and sleeve‐gastrectomy groups were superior to the changes seen in the medical‐therapy group with respect to body weight ( ‐23 % , ‐19 % , and ‐5 % in the gastric‐bypass , sleeve‐gastrectomy , and medical‐therapy groups , respectively ) , triglyceride level ( ‐40 % , ‐29 % , and ‐8 % ) , high‐density lipoprotein cholesterol level ( 32 % , 30 % , and 7 % ) , use of insulin ( ‐35 % , ‐34 % , and ‐13 % ) , and quality ‐of‐life measures ( general health score increases of 17 , 16 , and 0.3 ; scores on the R AND 36‐Item Health Survey ranged from 0 to 100 , with higher scores indicating better health ) ( P<0.05 for all comparisons ) . No major late surgical complications were reported except for one reoperation . CONCLUSIONS Five‐year outcome data showed that , among patients with type 2 diabetes and a BMI of 27 to 43  , bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing , or in some cases resolving , hyperglycemia . ( Funded by Ethicon Endo‐Surgery and others ; STAMPEDE Clinical Trials.gov number , NCT00432809 . Two groups of beneficial bacteria are dominant in the human gut , the Bacteroidetes and the Firmicutes . Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people , and that this proportion increases with weight loss on two types of low-calorie diet . Our findings indicate that obesity has a microbial component , which might have potential therapeutic implication Complex gene – environment interactions are considered important in the development of obesity . The composition of the gut microbiota can determine the efficacy of energy harvest from food and changes in dietary composition have been associated with changes in the composition of gut microbial population s. The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches , which have already allowed production of the first human gut microbial gene catalogue and stratifying individuals by their gut genomic profile into different enterotypes , but the analyses were carried out mainly in non-intervention setting s. To investigate the temporal relationships between food intake , gut microbiota and metabolic and inflammatory phenotypes , we conducted diet-induced weight-loss and weight-stabilization interventions in a study sample of 38 obese and 11 overweight individuals . Here we report that individuals with reduced microbial gene richness ( 40 % ) present more pronounced dys-metabolism and low- grade inflammation , as observed concomitantly in the accompanying paper . Dietary intervention  improves low gene richness and clinical phenotypes , but seems to be less efficient for inflammation variables in individuals with lower gene richness . Low gene richness may therefore have predictive potential for the efficacy of intervention CONTEXT It has been hypothesized that increased plasma bile acids ( BAs ) contribute to metabolic improvements after Roux-en-Y gastric bypass ( RYGB ) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones . OBJECTIVE The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis ( insulin secretion and sensitivity ) and energy metabolism ( resting energy expenditure and thyroid hormone axis ) . DESIGN , PARTICIPANTS , INTERVENTION , AND MAIN OUTCOME MEASURE : Eighteen extremely obese subjects were studied before and after 20 % weight loss , induced by either laparoscopic adjustable gastric b and ing ( LAGB ) ( n = 10 ) or RYGB surgery ( n = 8) . RESULTS Plasma BAs more than doubled after RYGB [ fasting : 1.08 ( 0.26 - 1.42 ) to 2.28 ( 1.59 - 3.28 ) μmol/L , P = .03 ; postpr and ial : 2.46 ± 1.59 to 6.00 ± 2.75 μmol/L , P = .01 ] but were either lower or did not change after LAGB [ fasting : 1.80 ( 1.49 - 2.19 ) to 0.92 ( 0.73 - 1.15 ) μmol/L , P = .02 ; postpr and ial : 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L , P = .14 ] . Skeletal muscle expression of TGR5 targets , Kir6.2 and cyclooxygenase IV , increased after RYGB but not LAGB . Surgery-induced changes in BAs were associated with increased peak postpr and ial plasma glucagon-like peptide-1 ( r(2 ) = 0.509 , P = .001 ) and decreased serum TSH ( r(2 ) = 0.562 , P < .001 ) but did not correlate with the change in insulin response to a meal ( r(2 ) = 0.013 , P = .658 ) , insulin sensitivity ( assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure ) ( r(2 ) = 0.001 , P = .995 ) , or resting energy expenditure ( r(2 ) = 0.004 , P = .807 ) . CONCLUSIONS Compared with LAGB , RYGB increases circulating BAs and TGR5 signaling , but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism
target: The findings support the effects of BAs on satiety , lipid and cholesterol metabolism , incretins and glucose homoeostasis , energy metabolism , gut microbiota and endoplasmic reticulum stress following bariatric surgery .
  Many of these metabolic effects are modulated through the BA receptors FXR and TGR5 .
  We also explore a possible link between BAs and carcinogenesis following bariatric surgery .
  Conclusions : Overall there is good evidence to support the role of BAs in the metabolic effects of bariatric surgery through the above mechanisms .
  BAs could serve as a novel therapeutic pharmacological target for the treatment of obesity and its associated co-morbidities
background: Background : Bariatric surgery is currently the most efficacious treatment for obesity and its associated metabolic co-morbidities , such as diabetes .
  The metabolic improvements occur through both weight-dependent and weight-independent mechanisms .
  Bile acids ( BAs ) have emerged as key signalling molecules that have a central role in modulating many of the physiological effects seen after bariatric surgery .
  This systematic review assesses the evidence from both human and animal studies for the role of BAs in reducing the metabolic complications of obesity following bariatric surgery .