| Autor: |
Jiao N; Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.; Department of Bioinformatics, Putuo People's Hospital, Tongji University, Shanghai, People's Republic of China., Loomba R; Division of Gastroenterology and Epidemiology, Department of Medicine, NAFLD Research Center, University of California San Diego, La Jolla, California., Yang ZH; Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China., Wu D; Department of Bioinformatics, Putuo People's Hospital, Tongji University, Shanghai, People's Republic of China., Fang S; Department of Bioinformatics, Putuo People's Hospital, Tongji University, Shanghai, People's Republic of China., Bettencourt R; Division of Gastroenterology and Epidemiology, Department of Medicine, NAFLD Research Center, University of California San Diego, La Jolla, California., Lan P; Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China., Zhu R; Department of Bioinformatics, Putuo People's Hospital, Tongji University, Shanghai, People's Republic of China., Zhu L; Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.; Department of Biochemistry, Genome, Environment and Microbiome Community of Excellence, The State University of New York at Buffalo, Buffalo, New York. |
| Abstrakt: |
Multiple mechanisms for the gut microbiome contributing to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) have been implicated. Here, we aim to investigate the contribution and potential application for altered bile acids (BA) metabolizing microbes in NAFLD by post hoc analysis of whole metagenome sequencing (WMS) data. The discovery cohort consisted of 86 well-characterized patients with biopsy-proven NAFLD and 38 healthy controls. Assembly-based analysis was performed to identify BA-metabolizing microbes. Statistical tests, feature selection, and microbial coabundance analysis were integrated to identify microbial alterations and markers in NAFLD. An independent validation cohort was subjected to similar analyses. NAFLD microbiota exhibited decreased diversity and microbial associations. We established a classifier model with 53 differential species exhibiting a robust diagnostic accuracy [area under the receiver-operator curve (AUC) = 0.97] for detecting NAFLD. Next, eight important differential pathway markers including secondary BA biosynthesis were identified. Specifically, increased abundance of 7α-hydroxysteroid dehydrogenase (7α-HSDH), 3α-hydroxysteroid dehydrogenase (baiA), and bile acid-coenzyme A ligase (baiB) was detected in NAFLD. Furthermore, 10 of 50 BA-metabolizing metagenome-assembled genomes (MAGs) from Bacteroides ovatus and Eubacterium biforme were dominant in NAFLD and interplayed as a synergetic ecological guild. Importantly, two subtypes of patients with NAFLD were observed according to secondary BA metabolism potentials. Elevated capability for secondary BA biosynthesis was also observed in the validation cohort. These bacterial BA-metabolizing genes and microbes identified in this study may serve as disease markers. Microbial differences in BA-metabolism and strain-specific differences among patients highlight the potential for precision medicine in NAFLD treatment. |
