A metagenome-wide association study of gut microbiome and visceral fat accumulation

Xiaomin Nie; Jiarui Chen; Xiaojing Ma; Yueqiong Ni; Yun Shen; Haoyong Yu; Gianni Panagiotou; Yuqian Bao

doi:10.1016/j.csbj.2020.09.026

A metagenome-wide association study of gut microbiome and visceral fat accumulation

Comput Struct Biotechnol J. 2020 Sep 20:18:2596-2609. doi: 10.1016/j.csbj.2020.09.026. eCollection 2020.

Authors

Xiaomin Nie¹, Jiarui Chen^{2

3}, Xiaojing Ma¹, Yueqiong Ni², Yun Shen¹, Haoyong Yu¹, Gianni Panagiotou^{2

3

4}, Yuqian Bao¹

Affiliations

¹ Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, China.
² Leibniz Institute for Natural Product Research and Infection Biology - Systems Biology and Bioinformatics, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745 Jena, Germany.
³ School of Biological Sciences, The University of Hong Kong, Kadoorie Biological Sciences Building, Pok Fu Lam Road, Hong Kong Special Administrative Region.
⁴ Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong Special Administrative Region.

Abstract

Purpose: Visceral fat is an independent risk factor for metabolic and cardiovascular disease. The study aimed to investigate the associations between gut microbiome and visceral fat.

Methods: We recruited 32 obese adults and 30 healthy controls at baseline. Among the obese subjects, 14 subjects underwent laparoscopic sleeve gastrectomy (LSG) and were followed 6 months after surgery. Abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by magnetic resonance imaging. Waist, hipline, waist-to-hip ratio (WHR) and body mass index (BMI) were included as simple obese parameters. Gut microbiome was analyzed by metagenomic sequencing.

Results: Among the obese parameters, VFA had the largest number of correlations with the species that were differentially enriched between obese and healthy subjects, following by waist, WHR, BMI, hipline, and SFA. Within the species negatively correlated with VFA, Eubacterium eligens had the strongest correlation, following by Clostridium citroniae, C. symbiosum, Bacteroides uniformis, E. ventriosum, Ruminococcaceae bacterium D16, C. hathewayi, etc. C. hathewayi and C. citroniae were increased after LSG. Functional analyses showed that among all the obese parameters, VFA had strongest correlation coefficients with the obesity-related microbial pathways. Microbial pathways involved in carbohydrate fermentation and biosynthesis of L-glutamate and L-glutamine might contribute to visceral fat accumulation.

Conclusions: Visceral fat was more closely correlated with gut microbiome compared with subcutaneous fat, suggesting an intrinsic connection between gut microbiome and metabolic cardiovascular diseases. Specific microbial species and pathways which were closely associated with visceral fat accumulation might contribute to new targeted therapies for metabolic disorders.

Keywords: 2hCP, 2-hour C-peptide; 2hPG, 2-hour plasma glucose; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCAAs, branched chain amino acids; BMI, body mass index; CoDA, Compositional Data Analysis; Cr, creatinine; DBP, diastolic blood pressure; FCp, fasting C-peptide; FDR, false discovery rate; FMT, fecal microbiota transplantation; FPG, fasting plasma glucose; GPR43, G-protein coupled receptor 43; Gut microbiome; HDL, high-density lipoprotein cholesterol; HbA1c, glycated hemoglobin A1c; LDL, low-density lipoprotein cholesterol; LPS, lipopolysaccharides; LSG, laparoscopic sleeve gastrectomy; Laparoscopic sleeve gastrectomy; MRI, magnetic resonance imaging; MSG, monosodium glutamate; Metagenomics; Obesity; SBP, systolic blood pressure; SCFAs, short chain fatty acids; SFA, subcutaneous fat area; TC, total cholesterol; TCA, tricarboxylic acid cycle; TG, triglyceride; UA, uric acid; VFA, visceral fat area; Visceral fat; WBC, white blood cell count; WHR, waist-to-hip ratio.