사업성과
연구성과
Gut microbiome signatures distinguish type 2 diabetes mellitus from non-alcoholic fatty liver disease
년도 2021
날짜 Oct
페이지 /
학회지명
19:5920-5930 / Computational and Structural Biotechnology Journal
논문저자 Jiyeon Si 1, Giljae Lee 2, Hyun Ju You 2 3, Sae Kyung Joo 4, Dong Hyeon Lee 4, Bon Jeong Ku 5, Seoyeon Park 2, Won Kim 4, GwangPyo Ko 2 6 7 8
Link 관련링크 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591343/ 201회 연결
Affiliations
1 Medical Science Research Institute, School of Medicine, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
2 Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea.
3 Institute of Health and Environment, Seoul National University, Seoul 08826, Republic of Korea.
4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Republic of Korea.
5 Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea.
6 Center for Human and Environmental Microbiome, Institute of Health and Environment, Seoul National University, Seoul 08826, Republic of Korea.
7 KoBioLabs, Inc., Seoul 08826, Republic of Korea.
8 Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Republic of Korea.

Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus (T2D), and these two metabolic diseases demonstrate bidirectional influences. The identification of microbiome profiles that are specific to liver injury or impaired glucose metabolism may assist understanding of the role of the gut microbiota in the relationship between NAFLD and T2D. Here, we studied a biopsy-proven Asian NAFLD cohort (n = 329; 187 participants with NAFLD, 101 with NAFLD and T2D, and 41 with neither) and identified Enterobacter, Romboutsia, and Clostridium sensu stricto as the principal taxa associated with the severity of NAFLD and T2D, whereas Ruminococcus and Megamonas were specific to NAFLD. In particular, the taxa that were associated with both severe liver pathology and T2D were also significantly associated with markers of diabetes, such as fasting blood glucose and Hb1Ac. Enterotype analysis demonstrated that participants with NAFLD had a significantly higher proportion of Bacteroides and a lower proportion of Ruminococcus than a Korean healthy twin cohort (n = 756). However, T2D could not be clearly distinguished from NAFLD. Analysis of an independent T2D cohort (n = 185) permitted us to validate the T2D-specific bacterial signature identified in the NAFLD cohort. Functional inference analysis revealed that endotoxin biosynthesis pathways were significantly enriched in participants with NAFLD and T2D, compared with those with NAFLD alone. These findings may assist with the development of effective therapeutic approaches for metabolic diseases that are associated with specific bacterial signatures.

Keywords: ALT, alanine aminotransferase; BMI, body mass index; Biomarker; Enterotype; FBS, fasting blood sugar; FDR, false discovery rate; FLI, fatty liver index; Gut microbiome; HbA1c, glycosylated hemoglobin; LDL, low-density lipoprotein; LPS, lipopolysaccharide; MaAsLin2, microbiome multivariable association with linear models 2; NAFL, non-alcoholic fatty liver; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; NASH-CRN, non-alcoholic steatohepatitis clinical research network; Non-alcoholic fatty liver disease (NAFLD); PICRUSt2, phylogenetic investigation of communities by reconstruction of unobserved states 2; T2D, type 2 diabetes mellitus; Type 2 diabetes mellitus.

서울대학교 보건대학원 환경보건학과 BK21연구단

TEL : 02) 880-2836