BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationsh...BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.展开更多
The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs.The bile acids with varying levels within two types of pigs were found and then in vitro exper...The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs.The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation.Fourteen pigs,including seven lean and seven obese pigs with body weights of approximately 80 kg,were fed the same diet at an amount approximately equivalent to 3%of their respective body weights daily for 42 d.In vitro,3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium.Then,bile acids were added to mature adipocytes for 4 d.The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs(P<0.05).According to the results of gut microbial function prediction,the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig.Sixty-five bile acids were further screened by metabolomics,of which 4 were upregulated(P<0.05)and 2 were downregulated(P<0.05)in obese pigs compared to lean pigs.The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-β-D-glucuronide(CDCA-3Gln)andω-muricholic acid(ω-MCA)had a negative correlation with abdominal fat weight and abdominal fat rate,while isoallolithocholic acid(IALCA)was positively associated with crude fat in the liver and abdominal fat rate.There was a positive correlation between loin muscle area and CDCA-3Gln andω-MCA(P<0.05),however,IALCA and 3-oxodeoxycholic acid(3-oxo-DCA)were negatively associated with loin eye muscle area(P<0.05).Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma(PPARG)and the number of lipid droplets(P<0.05),promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro.In conclusion,the concentration of bile acids,especially gut microbiota related-secondary bile acids,in obese pigs was different from that in lean pigs,which may contribute to lipid accumulation within obese pigs.展开更多
Background The liver manifestations of Alagille syndrome(ALGS)are highly variable,and factors affecting its prognosis are poorly understood.We asked whether the composition of bile acids in ALGS patients with good cli...Background The liver manifestations of Alagille syndrome(ALGS)are highly variable,and factors affecting its prognosis are poorly understood.We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.Methods Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age.A good prognosis was defined as survival with native liver and total bilirubin(TB)<85.5 μmol/L,while a poor prognosis was defined as either liver transplantation,death from liver failure,or TB ≥ 85.5 μmol/L at the last follow-up.Results We found that the concentrations of two poly-hydroxylated bile acids,tauro-2β,3α,7α,12α-tetrahydroxylated bile acid(THBA)and glyco-hyocholic acid(GHCA),were significantly increased in patients with good prognosis compared to those with poor prognosis[area under curve(AUC)=0.836 and 0.782,respectively]in the discovery cohort.The same trend was also observed in the molar ratios of GHCA to glyco-chenodeoxycholic acid(GCDCA)and tetrahydroxylated bile acid(THCA)to tauro-chenodeoxycholic acid(TCDCA)(both AUC=0.836).A validation cohort confirmed these findings.Notably,tauro-2β,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00%(92.31%sensitivity and 83.33%specificity);GHCA at>607.69 nmol/L was associated with native liver survival[hazard ratio:13.03,95%confidence interval(CI):(2.662-63.753),P=0.002].Conclusions We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients.Enhanced hydroxylation of bile acids may result in better clinical outcomes.展开更多
文摘BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.
基金funded by National Natural Science Foundation of China (31730091).
文摘The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs.The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation.Fourteen pigs,including seven lean and seven obese pigs with body weights of approximately 80 kg,were fed the same diet at an amount approximately equivalent to 3%of their respective body weights daily for 42 d.In vitro,3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium.Then,bile acids were added to mature adipocytes for 4 d.The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs(P<0.05).According to the results of gut microbial function prediction,the bile acid biosynthesis in colonic digesta of obese pigs were different from that in lean pig.Sixty-five bile acids were further screened by metabolomics,of which 4 were upregulated(P<0.05)and 2 were downregulated(P<0.05)in obese pigs compared to lean pigs.The results of the correlation analysis demonstrated that chenodeoxycholic acid-3-β-D-glucuronide(CDCA-3Gln)andω-muricholic acid(ω-MCA)had a negative correlation with abdominal fat weight and abdominal fat rate,while isoallolithocholic acid(IALCA)was positively associated with crude fat in the liver and abdominal fat rate.There was a positive correlation between loin muscle area and CDCA-3Gln andω-MCA(P<0.05),however,IALCA and 3-oxodeoxycholic acid(3-oxo-DCA)were negatively associated with loin eye muscle area(P<0.05).Isoallolithocholic acid increased the gene expression of peroxisome proliferator-activated receptor gamma(PPARG)and the number of lipid droplets(P<0.05),promoting the lipid storage when IALCA was added to 3T3-L1 mature adipocytes in vitro.In conclusion,the concentration of bile acids,especially gut microbiota related-secondary bile acids,in obese pigs was different from that in lean pigs,which may contribute to lipid accumulation within obese pigs.
基金Key Research and Development Program of China(No.2021YFC 2,700,800 to J-S W.National Natural Science Foundation of China(No.81741056 to WJS)National Natural Science Foundation of China(No.81873543 to WJS)Natural Science Foundation of Shanghai(20YF1402900 to T L).
文摘Background The liver manifestations of Alagille syndrome(ALGS)are highly variable,and factors affecting its prognosis are poorly understood.We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.Methods Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age.A good prognosis was defined as survival with native liver and total bilirubin(TB)<85.5 μmol/L,while a poor prognosis was defined as either liver transplantation,death from liver failure,or TB ≥ 85.5 μmol/L at the last follow-up.Results We found that the concentrations of two poly-hydroxylated bile acids,tauro-2β,3α,7α,12α-tetrahydroxylated bile acid(THBA)and glyco-hyocholic acid(GHCA),were significantly increased in patients with good prognosis compared to those with poor prognosis[area under curve(AUC)=0.836 and 0.782,respectively]in the discovery cohort.The same trend was also observed in the molar ratios of GHCA to glyco-chenodeoxycholic acid(GCDCA)and tetrahydroxylated bile acid(THCA)to tauro-chenodeoxycholic acid(TCDCA)(both AUC=0.836).A validation cohort confirmed these findings.Notably,tauro-2β,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00%(92.31%sensitivity and 83.33%specificity);GHCA at>607.69 nmol/L was associated with native liver survival[hazard ratio:13.03,95%confidence interval(CI):(2.662-63.753),P=0.002].Conclusions We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients.Enhanced hydroxylation of bile acids may result in better clinical outcomes.