Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans

Jessica-Miranda Bustamante, Department of Surgery, School of Medicine, Center for Alimentary and Metabolic Science, University of California, Sacramento, CA 95817, USA.
Tyson Dawson, Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
Caitlin Loeffler, Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
Zara Marfori, Department of Surgery, School of Medicine, Center for Alimentary and Metabolic Science, University of California, Sacramento, CA 95817, USA.
Julian R. Marchesi, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St. Mary's Hospital Campus, Imperial College London, London W2 1NY, UK.
Benjamin H. Mullish, Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St. Mary's Hospital Campus, Imperial College London, London W2 1NY, UK.
Christopher C. Thompson, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Keith A. Crandall, Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
Ali Rahnavard, Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
Jessica R. Allegretti, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Bethany P. Cummings, Department of Surgery, School of Medicine, Center for Alimentary and Metabolic Science, University of California, Sacramento, CA 95817, USA.

Document Type

Journal Article

Publication Date

12-7-2022

Journal

Nutrients

Volume

14

Issue

24

DOI

10.3390/nu14245200

Keywords

bile acids; bile salt hydrolase (BSH); fecal microbiome transplant (FMT); gut microbiota; metagenomics

Abstract

Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included and . To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. and were positively correlated with unconjugated bile acids. , , and were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.

Department

Biostatistics and Bioinformatics

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