Causal relationship between gut microbiota with subcutaneous and visceral adipose tissue: a bidirectional two-sample Mendelian Randomization study

Frontiers in Microbiology, vol. 14, pp. 1285982

Abstract

Background Numerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships with adipose tissue production in different regions of the body remain unclear. Methods We conducted a bidirectional two-sample Mendelian Randomization (MR) study using aggregated data from genome-wide association studies (GWAS) for gut microbiota and adipose tissue. We employed methods such as inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the causal relationships between gut microbiota and subcutaneous adipose tissue (SAT) as well as visceral adipose tissue (VAT). Cochran’s Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to test for heterogeneity, pleiotropy, and outliers of the instrumental variables, respectively. Reverse MR was employed to evaluate the reverse causal relationships between SAT, VAT, and gut microbiota with significant associations. Results IVW results demonstrated that Betaproteobacteria were protective factors for SAT production (OR = 0.88, 95% CI: 0.80–0.96, p = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83–0.99, p = 0.030). Various bacterial taxa including Ruminococcaceae UCG002 (OR = 0.94, 95% CI: 0.89–0.99, p = 0.017), Methanobacteria class (OR = 0.96, 95% CI: 0.92–1.00, p = 0.029), and Burkholderiales (OR = 0.90, 95% CI: 0.83–0.98, p = 0.012) were associated only with decreased SAT production. Rikenellaceae RC9 gut group (OR = 1.05, 95% CI: 1.02–1.10, p = 0.005), Eubacterium hallii group (OR = 1.08, 95% CI: 1.01–1.15, p = 0.028), Peptococcaceae (OR = 1.08, 95% CI: 1.01–1.17, p = 0.034), and Peptococcus (OR = 1.05, 95% CI: 1.00–1.10, p = 0.047) were risk factors for SAT production. Meanwhile, Eubacterium fissicatena group (OR = 0.95, 95% CI: 0.91–0.99, p = 0.019), Turicibacter (OR = 0.93, 95% CI: 0.88–0.99, p = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89–0.99, p = 0.024) were protective factors for VAT production. Furthermore, Bacteroidetes (OR = 1.09, 95% CI: 1.01–1.17, p = 0.018), Eubacterium eligens group (OR = 1.09, 95% CI: 1.01–1.19, p = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00–1.10, p = 0.038), and Phascolarctobacterium (OR = 1.07, 95% CI: 1.00–1.15, p = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and Rikenellaceae RC9 gut group (IVW: OR = 1.57, 95% CI: 1.18–2.09, p = 0.002) as well as Betaproteobacteria (IVW: OR = 1.14, 95% CI: 1.01–1.29, p = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy. Conclusion This study unveils complex causal relationships between gut microbiota and SAT/VAT, providing novel insights into the diagnostic and therapeutic potential of gut microbiota in obesity and related metabolic disorders.

Authors 7

1. Feng Cao Aachen Department of General Surgery

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of General Surgery, University Hospital RWTH Aachen, Aachen, Germany

   Department of General Surgery, University Hospital RWTH Aachen, Germany

2. Feng Pan

   Second Affiliated Hospital of Anhui Medical University · Anhui Medical University

   Affiliation as printed

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, China

3. Xin Gong

   Second Affiliated Hospital of Anhui Medical University · Anhui Medical University

   Affiliation as printed

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, China

4. Wen Wang

   Anhui Medical University · Anqing City Hospital

   Affiliation as printed

   Department of General Practice, Anqing Hospital Affiliated Hospital of Anhui Medical University, Anqing, China

   Department of General Practice, Anqing Hospital Affiliated Hospital of Anhui Medical University, China

5. Yanyan Xu

   Second Affiliated Hospital of Anhui Medical University · Anhui Medical University

   Affiliation as printed

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, China

6. Pengwei Cao corresponding

   Anhui Medical University · First Affiliated Hospital of Anhui Medical University

   Affiliation as printed

   Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China

   Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, China

7. Yong Wang corresponding

   Southern Medical University · Second Affiliated Hospital of Anhui Medical University · Anhui Medical University · Southern Medical University Shenzhen Hospital

   Affiliation as printed

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

   Department of General Surgery, The Shenzhen Hospital of Southern Medical University, Shenzhen, China

   Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, China

   Department of General Surgery, The Shenzhen Hospital of Southern Medical University, China