AUTHOR=Cao Feng , Pan Feng , Gong Xin , Wang Wen , Xu Yanyan , Cao Pengwei , Wang Yong 

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

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1285982

DOI=10.3389/fmicb.2023.1285982

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Background</title><p>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.</p></sec><sec id="sec2"><title>Methods</title><p>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.</p></sec><sec id="sec3"><title>Results</title><p>IVW results demonstrated that <italic>Betaproteobacteria</italic> were protective factors for SAT production (OR = 0.88, 95% CI: 0.80–0.96, <italic>p</italic> = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83–0.99, <italic>p</italic> = 0.030). Various bacterial taxa including <italic>Ruminococcaceae UCG002</italic> (OR = 0.94, 95% CI: 0.89–0.99, <italic>p</italic> = 0.017), <italic>Methanobacteria class</italic> (OR = 0.96, 95% CI: 0.92–1.00, <italic>p</italic> = 0.029), and <italic>Burkholderiales</italic> (OR = 0.90, 95% CI: 0.83–0.98, <italic>p</italic> = 0.012) were associated only with decreased SAT production. <italic>Rikenellaceae RC9 gut group</italic> (OR = 1.05, 95% CI: 1.02–1.10, <italic>p</italic> = 0.005), <italic>Eubacterium hallii group</italic> (OR = 1.08, 95% CI: 1.01–1.15, <italic>p</italic> = 0.028), <italic>Peptococcaceae</italic> (OR = 1.08, 95% CI: 1.01–1.17, <italic>p</italic> = 0.034), and <italic>Peptococcus</italic> (OR = 1.05, 95% CI: 1.00–1.10, <italic>p</italic> = 0.047) were risk factors for SAT production. Meanwhile, <italic>Eubacterium fissicatena group</italic> (OR = 0.95, 95% CI: 0.91–0.99, <italic>p</italic> = 0.019), <italic>Turicibacter</italic> (OR = 0.93, 95% CI: 0.88–0.99, <italic>p</italic> = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89–0.99, <italic>p</italic> = 0.024) were protective factors for VAT production. Furthermore, <italic>Bacteroidetes</italic> (OR = 1.09, 95% CI: 1.01–1.17, <italic>p</italic> = 0.018), <italic>Eubacterium eligens group</italic> (OR = 1.09, 95% CI: 1.01–1.19, <italic>p</italic> = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00–1.10, <italic>p</italic> = 0.038), and <italic>Phascolarctobacterium</italic> (OR = 1.07, 95% CI: 1.00–1.15, <italic>p</italic> = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and <italic>Rikenellaceae RC9 gut group</italic> (IVW: OR = 1.57, 95% CI: 1.18–2.09, <italic>p</italic> = 0.002) as well as <italic>Betaproteobacteria</italic> (IVW: OR = 1.14, 95% CI: 1.01–1.29, <italic>p</italic> = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy.</p></sec><sec id="sec4"><title>Conclusion</title><p>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.</p></sec>