Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus
Bile acids are a major component of gastro-esophageal refluxate, thought to contribute to the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). As the microbiome shifts with EAC progression and bile acids influence bacterial composition, we examined these connections in a...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2545420 |
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| author | Ceylan Tanes Yun Li Gary W. Falk Gregory G. Ginsberg Kenneth K. Wang Prasad G. Iyer Charles J. Lightdale Armando Del Portillo Stephen M. Lagana Timothy C. Wang Anil K. Rustgi Michael Quante Zhezhen Jin Gary D. Wu Elliot S. Friedman Kyle Bittinger Hongzhe Li Julian A. Abrams |
| author_facet | Ceylan Tanes Yun Li Gary W. Falk Gregory G. Ginsberg Kenneth K. Wang Prasad G. Iyer Charles J. Lightdale Armando Del Portillo Stephen M. Lagana Timothy C. Wang Anil K. Rustgi Michael Quante Zhezhen Jin Gary D. Wu Elliot S. Friedman Kyle Bittinger Hongzhe Li Julian A. Abrams |
| author_sort | Ceylan Tanes |
| collection | DOAJ |
| description | Bile acids are a major component of gastro-esophageal refluxate, thought to contribute to the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). As the microbiome shifts with EAC progression and bile acids influence bacterial composition, we examined these connections in a multi-center, cross-sectional study. We analyzed biospecimens from patients undergoing endoscopy using LC-MS to quantify bile acids in gastric aspirates, 16S rRNA sequencing for tissue microbiome profiling, and RNA sequencing on BE or cardia tissue. Among 153 patients (52 controls, 101 BE: 50 no dysplasia, 10 indefinite, 17 low-grade dysplasia, 17 high-grade dysplasia, and 7 EAC), we observed increased Streptococcus in BE tissue; dysplasia and EAC were associated with more Lactobacillus and decreased Actinomyces and other genera. Refluxate bile acids were mainly conjugated, indicating minimal bacterial metabolism, while BE patients had elevated secondary bile acid levels. Streptococcus correlated with upregulation of IL6, FGF2, and HGF, and decreased Actinomyces showed the most associations with gene expression, including the oxidative phosphorylation pathway. We identified two distinct BE gene expression clusters independent of histology, bile acid, or microbiome composition. These findings suggest bile acids shape the BE microbiome and associate with gene expression changes potentially relevant to EAC development. |
| format | Article |
| id | doaj-art-dbfd5e12b94f4db8bb2a53b84ce25d30 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-dbfd5e12b94f4db8bb2a53b84ce25d302025-08-22T13:15:10ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2545420Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagusCeylan Tanes0Yun Li1Gary W. Falk2Gregory G. Ginsberg3Kenneth K. Wang4Prasad G. Iyer5Charles J. Lightdale6Armando Del Portillo7Stephen M. Lagana8Timothy C. Wang9Anil K. Rustgi10Michael Quante11Zhezhen Jin12Gary D. Wu13Elliot S. Friedman14Kyle Bittinger15Hongzhe Li16Julian A. Abrams17Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USADepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADivision of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADivision of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USADivision of Digestive & Liver Diseases, Columbia University Irving Medical Center, New York, NY, USADepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USADepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USADivision of Digestive & Liver Diseases, Columbia University Irving Medical Center, New York, NY, USADivision of Digestive & Liver Diseases, Columbia University Irving Medical Center, New York, NY, USADepartment of Medicine II, University of Freiburg, Freiburg, GermanyDepartment of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USADivision of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADivision of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADivision of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USADepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADivision of Digestive & Liver Diseases, Columbia University Irving Medical Center, New York, NY, USABile acids are a major component of gastro-esophageal refluxate, thought to contribute to the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). As the microbiome shifts with EAC progression and bile acids influence bacterial composition, we examined these connections in a multi-center, cross-sectional study. We analyzed biospecimens from patients undergoing endoscopy using LC-MS to quantify bile acids in gastric aspirates, 16S rRNA sequencing for tissue microbiome profiling, and RNA sequencing on BE or cardia tissue. Among 153 patients (52 controls, 101 BE: 50 no dysplasia, 10 indefinite, 17 low-grade dysplasia, 17 high-grade dysplasia, and 7 EAC), we observed increased Streptococcus in BE tissue; dysplasia and EAC were associated with more Lactobacillus and decreased Actinomyces and other genera. Refluxate bile acids were mainly conjugated, indicating minimal bacterial metabolism, while BE patients had elevated secondary bile acid levels. Streptococcus correlated with upregulation of IL6, FGF2, and HGF, and decreased Actinomyces showed the most associations with gene expression, including the oxidative phosphorylation pathway. We identified two distinct BE gene expression clusters independent of histology, bile acid, or microbiome composition. These findings suggest bile acids shape the BE microbiome and associate with gene expression changes potentially relevant to EAC development.https://www.tandfonline.com/doi/10.1080/19490976.2025.2545420Barrett’s esophagusesophageal adenocarcinomabile acidsmicrobiome |
| spellingShingle | Ceylan Tanes Yun Li Gary W. Falk Gregory G. Ginsberg Kenneth K. Wang Prasad G. Iyer Charles J. Lightdale Armando Del Portillo Stephen M. Lagana Timothy C. Wang Anil K. Rustgi Michael Quante Zhezhen Jin Gary D. Wu Elliot S. Friedman Kyle Bittinger Hongzhe Li Julian A. Abrams Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus Gut Microbes Barrett’s esophagus esophageal adenocarcinoma bile acids microbiome |
| title | Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus |
| title_full | Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus |
| title_fullStr | Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus |
| title_full_unstemmed | Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus |
| title_short | Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett’s esophagus |
| title_sort | increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in barrett s esophagus |
| topic | Barrett’s esophagus esophageal adenocarcinoma bile acids microbiome |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2545420 |
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