Identification of Causal Pathways among Gut Microbiota, Food Intake and Telomere Length: A Mendelian Randomization Study

Background: Dietary habit plays an important role in the composition and function of gut microbiota which possibly manipulates host eating behavior. Gut microflora and nutritional imbalance are associated with telomere length (TL). However, the causality among them remains unclear. We aim to explore the causal pathways among gut microbiota, food intake (FI) and TL. Results: : Firstly, we calculate the significance threshold based on genetic correlations.Then we perform bi-directional Mendelian Randomization (MR) analyses among 82 FIs (UK Biobank, N=455,146), 95 gut microbial traits (Flemish Gut Flora Project, N=2,223) and TL (genome-wide meta-analysis from 15 cohorts, N=37,684) using summary-level data from large genome-wide association studies. Fixed-effect inverse variance weighting is the main analysis method and the other eight two-sample MR methods and three sensitivity analyses are performed. Several bi-directional causal relationships among gut microbiota, FIs and TL are obtained by two-sample MR. Overall, we find suggestive evidence of three main causal pathways among them. Drinking more glasses of water per day is able to affect the habit of eating dried fruit through the host gut microbiota (Barnesiella). The change of one gut microbiota taxon (Collinsella) in the host causally influences another gut microbiota taxon (Lactonccus) through the diet habits (intake of oil-based spread). Additionally, the TL alters the habits of drinking ground coffee and further affects the gut microbiota (Acidaminococcaceae). Finally, GO enrichment analyses are used to investigate the bio-function and confirm the MR results. Conclusions: TL has an impact on diet habits and gut microbiota and there are bi-directional relationships between diet habits and gut microbiota.