Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile Acids
The perturbations in bile acids (BAs) in alcohol‐associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the r...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2022-05-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1885 |
| _version_ | 1797758980233101312 |
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| author | Mark D. Muthiah Ekaterina Smirnova Puneet Puri Naga Chalasani Vijay H. Shah Calvin Kiani Stephanie Taylor Faridoddin Mirshahi Arun J. Sanyal |
| author_facet | Mark D. Muthiah Ekaterina Smirnova Puneet Puri Naga Chalasani Vijay H. Shah Calvin Kiani Stephanie Taylor Faridoddin Mirshahi Arun J. Sanyal |
| author_sort | Mark D. Muthiah |
| collection | DOAJ |
| description | The perturbations in bile acids (BAs) in alcohol‐associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the relationship of these changes to disease severity. In this multicenter study, plasma and fecal BAs and related microbiome were interrogated in healthy individuals, heavy drinking controls (HDCs) without overt liver disease, and AH. Compared to healthy controls, HDCs had increased glycine‐conjugated 7α and 27α primary BAs and increased secondary BA glycocholenic sulfate (multiple‐comparison adjusted P < 0.05 for all). Plasma‐conjugated cholic and chenodeoxycholic acid increased in AH along with the secondary BAs ursodeoxycholic and lithocholic acid (P < 0.001 for all), whereas deoxycholic acid decreased; however fecal concentrations of both deoxycholic acid and lithocholic acid were decreased. Glycocholenic acid further increased significantly from HDCs to AH. HDCs and AH had distinct plasma and fecal BA profiles (area under the curve, 0.99 and 0.93, respectively). Plasma taurochenodeoxycholic acid and tauroursodeoxycholic acid were directly related to disease severity, whereas fecal ursodeoxycholic acid was inversely related. The fecal abundance of multiple taxa involved in formation of secondary BAs, especially deoxycholic acid (Clostridium cluster XIVa) was decreased in AH. Multiple genera containing taxa expressing 3α, 3β, 7α, and 7β epimerases were decreased with concordant changes in fecal BAs that required these functions for formation. Conclusion: There are distinct changes in BA‐transforming microbiota and corresponding BAs in AH that are related to disease severity. |
| first_indexed | 2024-03-12T18:37:49Z |
| format | Article |
| id | doaj.art-5ba72c522fbc46c18e6bf22c0522b8cf |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-03-12T18:37:49Z |
| publishDate | 2022-05-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-5ba72c522fbc46c18e6bf22c0522b8cf2023-08-02T07:55:56ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2022-05-01651073108910.1002/hep4.1885Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile AcidsMark D. Muthiah0Ekaterina Smirnova1Puneet Puri2Naga Chalasani3Vijay H. Shah4Calvin Kiani5Stephanie Taylor6Faridoddin Mirshahi7Arun J. Sanyal8Department of Medicine Yong Loo Lin School of MedicineNational University of Singapore SingaporeDepartment of Biostatistics Virginia Commonwealth University Richmond VA USADivision of Gastroenterology, Hepatology, and Nutrition Department of Internal Medicine Virginia Commonwealth University Richmond VA USADivision of Gastroenterology Department of Internal Medicine Indiana University Indianapolis IN USADivision of Gastroenterology Department of Internal Medicine Mayo Clinic Rochester MN USADivision of Gastroenterology, Hepatology, and Nutrition Department of Internal Medicine Virginia Commonwealth University Richmond VA USADivision of Gastroenterology, Hepatology, and Nutrition Department of Internal Medicine Virginia Commonwealth University Richmond VA USADivision of Gastroenterology, Hepatology, and Nutrition Department of Internal Medicine Virginia Commonwealth University Richmond VA USADivision of Gastroenterology, Hepatology, and Nutrition Department of Internal Medicine Virginia Commonwealth University Richmond VA USAThe perturbations in bile acids (BAs) in alcohol‐associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the relationship of these changes to disease severity. In this multicenter study, plasma and fecal BAs and related microbiome were interrogated in healthy individuals, heavy drinking controls (HDCs) without overt liver disease, and AH. Compared to healthy controls, HDCs had increased glycine‐conjugated 7α and 27α primary BAs and increased secondary BA glycocholenic sulfate (multiple‐comparison adjusted P < 0.05 for all). Plasma‐conjugated cholic and chenodeoxycholic acid increased in AH along with the secondary BAs ursodeoxycholic and lithocholic acid (P < 0.001 for all), whereas deoxycholic acid decreased; however fecal concentrations of both deoxycholic acid and lithocholic acid were decreased. Glycocholenic acid further increased significantly from HDCs to AH. HDCs and AH had distinct plasma and fecal BA profiles (area under the curve, 0.99 and 0.93, respectively). Plasma taurochenodeoxycholic acid and tauroursodeoxycholic acid were directly related to disease severity, whereas fecal ursodeoxycholic acid was inversely related. The fecal abundance of multiple taxa involved in formation of secondary BAs, especially deoxycholic acid (Clostridium cluster XIVa) was decreased in AH. Multiple genera containing taxa expressing 3α, 3β, 7α, and 7β epimerases were decreased with concordant changes in fecal BAs that required these functions for formation. Conclusion: There are distinct changes in BA‐transforming microbiota and corresponding BAs in AH that are related to disease severity.https://doi.org/10.1002/hep4.1885 |
| spellingShingle | Mark D. Muthiah Ekaterina Smirnova Puneet Puri Naga Chalasani Vijay H. Shah Calvin Kiani Stephanie Taylor Faridoddin Mirshahi Arun J. Sanyal Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile Acids Hepatology Communications |
| title | Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile Acids |
| title_full | Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile Acids |
| title_fullStr | Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile Acids |
| title_full_unstemmed | Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile Acids |
| title_short | Development of Alcohol‐Associated Hepatitis Is Associated With Specific Changes in Gut‐Modified Bile Acids |
| title_sort | development of alcohol associated hepatitis is associated with specific changes in gut modified bile acids |
| url | https://doi.org/10.1002/hep4.1885 |
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