human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively . However , the effects of diets high in whole versus refined grains on circulating bile acids , which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor ( FXR ) and G protein-coupled bile acid receptor 1 ( TGR5 ) , have not been studied . MATERIAL S AND METHODS We conducted a secondary analysis from a r and omized controlled crossover feeding trial ( NCT00622661 ) in 80 healthy adults ( 40 women/40 men , age 18 - 45 years ) from the greater Seattle Area , half of which were normal weight ( BMI 18.5 - 25.0 kg/m2 ) and half overweight to obese ( BMI 28.0 - 39.9 kg/m2 ) . Participants consumed two four-week controlled diets in r and omized order : 1 ) a whole grain diet ( WG diet ) , design ed to be low in glycemic load ( GL ) , high in whole grains , legumes , and fruits and vegetables , and 2 ) a refined grain diet ( RG diet ) , design ed to be high GL , high in refined grains and added sugars , separated by a four-week washout period . Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography t and em mass spectrometry . Concentrations of glucose , insulin , and CRP were measured in fasting serum . Linear mixed models were used to test the effects of diet on bile acid concentrations , and determine the association between plasma bile acid concentrations and HOMA-IR and CRP . Benjamini-Hochberg false discovery rate ( FDR ) < 0.05 was used to control for multiple testing . RESULTS A total of 29 plasma bile acids were reliably detected and retained for analysis . Taurolithocholic acid ( TLCA ) , taurocholic acid ( TCA ) and glycocholic acid ( GCA ) were statistically significantly higher after the WG compared to the RG diet ( FDR < 0.05 ) . There were no significant differences by BMI or sex . When evaluating the association of bile acids and HOMA-IR , GCA , taurochenodeoxycholic acid , ursodeoxycholic acid ( UDCA ) , 5β‑cholanic acid‑3β,12α‑diol , 5‑cholanic acid‑3β‑ol , and glycodeoxycholic acid ( GDCA ) were statistically significantly positively associated with HOMA-IR individually , and as a group , total , 12α‑hydroxylated , primary and secondary bile acids were also significant ( FDR < 0.05 ) . When stratifying by BMI , chenodeoxycholic acid ( CDCA ) , cholic acid ( CA ) , UDCA , 5β-cholanic acid-3β , deoxycholic acid , and total , 12α-hydroxylated , primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals ( FDR < 0.05 ) . When stratifying by sex , GCA , CDCA , TCA , CA , UDCA , GDCA , glycolithocholic acid ( GLCA ) , total , primary , 12α‑hydroxylated , and glycine-conjugated bile acids were significantly associated with HOMA-IR among women , and CDCA , GDCA , and GLCA were significantly associated among men ( FDR < 0.05 ) . There were no significant associations between bile acids and CRP . CONCLUSIONS Diets with comparable macronutrient and energy composition , but differing in carbohydrate source , affected fasting plasma bile acids differently . Specifically , a diet characterized by whole grains , legumes , and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA , TCA and GCA , lig and s for FXR and TGR5 , which may have beneficial effects on glucose homeostasis Background Bile acids ( BAs ) are post-pr and ial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure . Total and glycine-ami date d BAs increase after sleeve gastrectomy ( SG ) and correlate to improved metabolic disease . No specific bile acid subtype has been shown conclusively to mediate the weight loss effect . Therefore , the objective of this study was to prospect ively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response . Methods Patients were prospect ively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity . Primary and secondary plasma bile acids and their ami date d ( glycine , G- , or taurine , T- ) subtypes were measured at fasting , 30 and 60 min after a liquid meal performed pre-op , and at 6 and 12 weeks post-op . Area under the curve ( AUC ) was calculated for the hour meal test for each bile acid subtype . BAs that were significantly increased post-op were correlated to body mass index ( BMI ) loss . Results Total BA AUC was significantly increased at 6 ( p < 0.01 ) and 12 weeks post-op ( p < 0.01 ) compared to pre-operative values . The increase in total BA AUC was due to a statistically significant increase in G-BAs . Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op . Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss ( p = 0.03 ) . Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 ( p = 0.05 ) and 12 weeks ( p = 0.006 ) . Conclusions SG induced an early and persistent post-pr and ial surge in multiple bile acid subtypes . Increased G-hyocholic consistently correlated with greater early BMI loss . This study provides evidence for a role of BAs in the surgical weight loss response after SG 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 Summary Bariatric surgery is currently the most effective procedure for the treatment of obesity . Given the role of the gut microbiota in regulating host metabolism and adiposity , we investigated the long-term effects of bariatric surgery on the microbiome of patients r and omized to Roux-en-Y gastric bypass or vertical b and ed gastroplasty and matched for weight and fat mass loss . The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and result ed in altered levels of fecal and circulating metabolites compared with obese controls . By colonizing germ-free mice with stools from the patients , we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice . These mice also had a lower respiratory quotient , indicating decreased utilization of carbohydrates as fuel . Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction . Laparoscopic sleeve gastrectomy ( LSG ) , a surgical intervention for obesity , is classified as predominantly restrictive procedure . In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects ( n = 5 per group ) demonstrating identical weight loss during a follow-up period of six months . For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics . The energy-reabsorbing potential of the gut microbiota decreased following LSG , indicated by the Bacteroidetes/Firmicutes ratio , but increased during diet . Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups . No alteration of faecal butyrate was observed , but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention . LSG result ed in enhanced faecal excretion of nonesterified fatty acids and bile acids .  LSG , but not dietetic restriction , improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype . Moreover , LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation . This trial is registered with Clinical Trials.gov NCT01344525 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 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 2 
    Output:
    
agent
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 .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively . However , the effects of diets high in whole versus refined grains on circulating bile acids , which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor ( FXR ) and G protein-coupled bile acid receptor 1 ( TGR5 ) , have not been studied . MATERIAL S AND METHODS We conducted a secondary analysis from a r and omized controlled crossover feeding trial ( NCT00622661 ) in 80 healthy adults ( 40 women/40 men , age 18 - 45 years ) from the greater Seattle Area , half of which were normal weight ( BMI 18.5 - 25.0 kg/m2 ) and half overweight to obese ( BMI 28.0 - 39.9 kg/m2 ) . Participants consumed two four-week controlled diets in r and omized order : 1 ) a whole grain diet ( WG diet ) , design ed to be low in glycemic load ( GL ) , high in whole grains , legumes , and fruits and vegetables , and 2 ) a refined grain diet ( RG diet ) , design ed to be high GL , high in refined grains and added sugars , separated by a four-week washout period . Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography t and em mass spectrometry . Concentrations of glucose , insulin , and CRP were measured in fasting serum . Linear mixed models were used to test the effects of diet on bile acid concentrations , and determine the association between plasma bile acid concentrations and HOMA-IR and CRP . Benjamini-Hochberg false discovery rate ( FDR ) < 0.05 was used to control for multiple testing . RESULTS A total of 29 plasma bile acids were reliably detected and retained for analysis . Taurolithocholic acid ( TLCA ) , taurocholic acid ( TCA ) and glycocholic acid ( GCA ) were statistically significantly higher after the WG compared to the RG diet ( FDR < 0.05 ) . There were no significant differences by BMI or sex . When evaluating the association of bile acids and HOMA-IR , GCA , taurochenodeoxycholic acid , ursodeoxycholic acid ( UDCA ) , 5β‑cholanic acid‑3β,12α‑diol , 5‑cholanic acid‑3β‑ol , and glycodeoxycholic acid ( GDCA ) were statistically significantly positively associated with HOMA-IR individually , and as a group , total , 12α‑hydroxylated , primary and secondary bile acids were also significant ( FDR < 0.05 ) . When stratifying by BMI , chenodeoxycholic acid ( CDCA ) , cholic acid ( CA ) , UDCA , 5β-cholanic acid-3β , deoxycholic acid , and total , 12α-hydroxylated , primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals ( FDR < 0.05 ) . When stratifying by sex , GCA , CDCA , TCA , CA , UDCA , GDCA , glycolithocholic acid ( GLCA ) , total , primary , 12α‑hydroxylated , and glycine-conjugated bile acids were significantly associated with HOMA-IR among women , and CDCA , GDCA , and GLCA were significantly associated among men ( FDR < 0.05 ) . There were no significant associations between bile acids and CRP . CONCLUSIONS Diets with comparable macronutrient and energy composition , but differing in carbohydrate source , affected fasting plasma bile acids differently . Specifically , a diet characterized by whole grains , legumes , and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA , TCA and GCA , lig and s for FXR and TGR5 , which may have beneficial effects on glucose homeostasis Background Bile acids ( BAs ) are post-pr and ial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure . Total and glycine-ami date d BAs increase after sleeve gastrectomy ( SG ) and correlate to improved metabolic disease . No specific bile acid subtype has been shown conclusively to mediate the weight loss effect . Therefore , the objective of this study was to prospect ively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response . Methods Patients were prospect ively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity . Primary and secondary plasma bile acids and their ami date d ( glycine , G- , or taurine , T- ) subtypes were measured at fasting , 30 and 60 min after a liquid meal performed pre-op , and at 6 and 12 weeks post-op . Area under the curve ( AUC ) was calculated for the hour meal test for each bile acid subtype . BAs that were significantly increased post-op were correlated to body mass index ( BMI ) loss . Results Total BA AUC was significantly increased at 6 ( p < 0.01 ) and 12 weeks post-op ( p < 0.01 ) compared to pre-operative values . The increase in total BA AUC was due to a statistically significant increase in G-BAs . Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op . Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss ( p = 0.03 ) . Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 ( p = 0.05 ) and 12 weeks ( p = 0.006 ) . Conclusions SG induced an early and persistent post-pr and ial surge in multiple bile acid subtypes . Increased G-hyocholic consistently correlated with greater early BMI loss . This study provides evidence for a role of BAs in the surgical weight loss response after SG 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 Summary Bariatric surgery is currently the most effective procedure for the treatment of obesity . Given the role of the gut microbiota in regulating host metabolism and adiposity , we investigated the long-term effects of bariatric surgery on the microbiome of patients r and omized to Roux-en-Y gastric bypass or vertical b and ed gastroplasty and matched for weight and fat mass loss . The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and result ed in altered levels of fecal and circulating metabolites compared with obese controls . By colonizing germ-free mice with stools from the patients , we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice . These mice also had a lower respiratory quotient , indicating decreased utilization of carbohydrates as fuel . Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction . Laparoscopic sleeve gastrectomy ( LSG ) , a surgical intervention for obesity , is classified as predominantly restrictive procedure . In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects ( n = 5 per group ) demonstrating identical weight loss during a follow-up period of six months . For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics . The energy-reabsorbing potential of the gut microbiota decreased following LSG , indicated by the Bacteroidetes/Firmicutes ratio , but increased during diet . Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups . No alteration of faecal butyrate was observed , but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention . LSG result ed in enhanced faecal excretion of nonesterified fatty acids and bile acids .  LSG , but not dietetic restriction , improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype . Moreover , LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation . This trial is registered with Clinical Trials.gov NCT01344525 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 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 2 
    Output:
    