Aarti Kumar, Pranav Gwalani, Prasad G Iyer, Kenneth K Wang, Gary W Falk, Gregory G Ginsberg, Charles J Lightdale, Armando Del Portillo, Stephen M Lagana, Yun Li, Hongzhe Li, Jeanine Genkinger, Zhezhen Jin, Anil K Rustgi, Timothy C Wang, Harris H Wang, Michael Quante, Julian A Abrams
{"title":"与巴雷特食管和食管腺癌进展阶段相关的血清胆汁酸谱变化","authors":"Aarti Kumar, Pranav Gwalani, Prasad G Iyer, Kenneth K Wang, Gary W Falk, Gregory G Ginsberg, Charles J Lightdale, Armando Del Portillo, Stephen M Lagana, Yun Li, Hongzhe Li, Jeanine Genkinger, Zhezhen Jin, Anil K Rustgi, Timothy C Wang, Harris H Wang, Michael Quante, Julian A Abrams","doi":"10.14309/ctg.0000000000000762","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression.</p><p><strong>Methods: </strong>Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression.</p><p><strong>Results: </strong>A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11-3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04-3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes.</p><p><strong>Discussion: </strong>Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500780/pdf/","citationCount":"0","resultStr":"{\"title\":\"Shifts in Serum Bile Acid Profiles Associated With Barrett's Esophagus and Stages of Progression to Esophageal Adenocarcinoma.\",\"authors\":\"Aarti Kumar, Pranav Gwalani, Prasad G Iyer, Kenneth K Wang, Gary W Falk, Gregory G Ginsberg, Charles J Lightdale, Armando Del Portillo, Stephen M Lagana, Yun Li, Hongzhe Li, Jeanine Genkinger, Zhezhen Jin, Anil K Rustgi, Timothy C Wang, Harris H Wang, Michael Quante, Julian A Abrams\",\"doi\":\"10.14309/ctg.0000000000000762\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. 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Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11-3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04-3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes.</p><p><strong>Discussion: </strong>Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.</p>\",\"PeriodicalId\":10278,\"journal\":{\"name\":\"Clinical and Translational Gastroenterology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500780/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.14309/ctg.0000000000000762\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.14309/ctg.0000000000000762","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
导言:反流胆汁酸被认为会促进EAC,但全身胆汁酸的作用尚不清楚。本研究旨在评估全身胆汁酸与巴雷特食管(BE)进展阶段之间的关系:这项多中心横断面研究招募了患有和未患有BE的受试者。方法:这项多中心横断面研究招募了患有和未患有BE的受试者,进行了有针对性的血清胆汁酸分析,一部分受试者填写了有效的食物频率问卷。对 BE 或胃贲门组织进行了 RNA 测序,以评估胆汁酸与基因表达的关系:结果:141名受试者的血清胆汁酸得到分析(49名非BE受试者;92名BE受试者:44名无发育不良,25名不确定/低度发育不良,23名高度发育不良/EAC)。健康饮食指数得分较低、年龄较大、体重指数较高以及未使用质子泵抑制剂与多种胆汁酸水平升高有关。非胆汁瘤和胆汁瘤各期之间的总体胆汁酸库是不同的(p=0.004)。与非 BE 相比,胆汁酸的增加与高级别发育不良/EAC 相关,即使在调整了 EAC 风险因素后也是如此(aOR 2.03,95% CI 1.11-3.71),非结合型初级胆汁酸的组合也是如此(aOR 1.81,95% CI 1.04-3.13)。高胆汁酸水平与组织基因表达变化有关,包括 DNA 复制增加和淋巴细胞分化基因减少:讨论:血清胆汁酸的变化与BE晚期肿瘤独立相关,并可能导致肿瘤进展。未来的研究应探讨相关的肠道微生物组变化、胆汁酸的促肿瘤作用,以及这些胆汁酸(尤其是胆酸)是否代表潜在的生物标志物或治疗 BE 晚期肿瘤的可行靶点。
Shifts in Serum Bile Acid Profiles Associated With Barrett's Esophagus and Stages of Progression to Esophageal Adenocarcinoma.
Introduction: Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression.
Methods: Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression.
Results: A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11-3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04-3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes.
Discussion: Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.
期刊介绍:
Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease.
Colon and small bowel
Endoscopy and novel diagnostics
Esophagus
Functional GI disorders
Immunology of the GI tract
Microbiology of the GI tract
Inflammatory bowel disease
Pancreas and biliary tract
Liver
Pathology
Pediatrics
Preventative medicine
Nutrition/obesity
Stomach.