| Title: | Mendelian Randomization Analysis Reveals Causal Effects of the Human Gut Microbiota on Abdominal Obesity |
| Journal: | Journal of Nutrition |
| Published: | 1 Jun 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33768223/ |
| DOI: | https://doi.org/10.1093/jn/nxab025 |
| URL: | https://academic.oup.com/jn/article-pdf/151/6/1401/38444227/nxab025.pdf |
| Citations: | 15 (11 in last 2 years) as of 8 Aug 2024 |
Publication 5375
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Abstract
BACKGROUND: Although recent studies have revealed an association between the composition of the gut microbiota and obesity, whether specific gut microbiota cause obesity has not been determined.</p>
OBJECTIVES: The aim of this study is to determine the causal relationship between specific gut microbiota and abdominal obesity. Based on genome-wide association study (GWAS) summary statistics, we performed a 2-sample Mendelian randomization (MR) analysis to evaluate whether the gut microbiota affects abdominal obesity.</p>
METHODS: Gut microbiota GWAS in 1126 twin pairs (age range, 18-89 years; 89% were females) from the TwinsUK study were used as exposure data. The primary outcome tested was trunk fat mass (TFM) GWAS in 492,805 participants (age range, 40-69 years; 54% were females) from the UK Biobank. The gut microbiota were classified at family, genus, and species levels. A feature was defined as a distinct family, genus, or species. MR analysis was mainly performed by an inverse variance-weighted test or Wald ratio test, depending on the number of instrumental variables (IVs) involved. A sensitivity analysis was performed on significant results by a weighted median test and a weighted genetic risk score (GRS) analysis.</p>
RESULTS: Results of MR analyses provided evidence of a causal association between 3 microbiota features and TFM, including 1 family [Lachnosiraceae; P = 0.02; β = 0.001 (SEE, 4.28 × 10-4)], 1 genus [Bifidobacterium; P = 5.0 × 10-9; β = -0.08 (SEE, 0.14)], and 1 species [Prausnitzii; P = 0.03; β = -0.007 (SEE, 0.003)]. Both the weighted median test and GRS analysis successfully validated the association of the genetically predicted family, Lachnosiraceae (Pweighted median = 0.03; PGRS = 0.004).</p>
CONCLUSIONS: Our findings provided evidence of a causal association between gut microbiota and TFM in UK adults and identified specific bacteria taxa that may regulate the fat metabolism, thus offering new direction for the treatment of obesity.</p>
13 Keywords
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Female
- Gastrointestinal Microbiome
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Obesity, Abdominal
- Young Adult
10 Authors
- Qian Xu
- Shan-Shan Zhang
- Rui-Rui Wang
- Yu-Jing Weng
- Xun Cui
- Xin-Tong Wei
- Jing-Jing Ni
- Hai-Gang Ren
- Lei Zhang
- Yu-Fang Pei
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