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

Feng Cao; Feng Pan; Xin Gong; Wen Wang; Yanyan Xu; Pengwei Cao; Yong Wang

doi:10.3389/fmicb.2023.1285982

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

Front Microbiol. 2023 Oct 31:14:1285982. doi: 10.3389/fmicb.2023.1285982. eCollection 2023.

Authors

Feng Cao^#¹, Feng Pan^#², Xin Gong^#², Wen Wang³, Yanyan Xu², Pengwei Cao⁴, Yong Wang^{2

5}

Affiliations

¹ Department of General Surgery, University Hospital RWTH Aachen, Aachen, Germany.
² Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
³ Department of General Practice, Anqing Hospital Affiliated Hospital of Anhui Medical University, Anqing, China.
⁴ Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
⁵ Department of General Surgery, The Shenzhen Hospital of Southern Medical University, Shenzhen, China.

^# Contributed equally.

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.

Keywords: Mendelian Randomization; causal inference; gut microbiota; subcutaneous adipose; visceral adipose.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by The Research Projects of Anhui Medical University, grant number: no. 2022xkj173, and Key Research and Development Program of Anhui Province, grant number: no. 2022e07020049.