Gut Microbiome and Atherosclerosis: A Mendelian Randomization Study

Abstract

Background: According to recent studies, atherosclerosis and gut microbiota are related. Nevertheless, it has been discovered that the gut microbiota varies across studies, with its function still being debated, and such relationships not proven to be causal. Thus, our study aimed to identify the key gut microbiota taxa (GM taxa) at different taxonomic levels, namely, the phylum, class, order, family, and genus, to investigate any potential causal links to atherosclerosis. Methods: We employed summary data from the MiBioGen consortium on the gut microbiota to conduct a sophisticated two-sample Mendelian randomization (MR) analysis. Pertinent information regarding atherosclerosis statistics was acquired from the FinnGen Consortium R8 publication. To assess causality, the utilized principal analytical technique was the inverse variance-weighted (IVW) method. Supplementary to IVW, additional MR methodologies were employed, including weighted median, MR-Egger, weighted methods, and simple mode. Sensitivity analyses involved the application of Cochrane’s Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Results: Finally, after performing an MR study on the risk of 211 GM taxa on atherosclerosis, we discovered 20 nominal links and one strong causal link. Firmicutes (phylum ID: 1672) (odds ratio (OR) = 0.852 (0.763, 0.950), p = 0.004) continued to be connected with a lower incidence of coronary atherosclerosis, even after Bonferroni correction. Conclusions: Based on the discovered data, it was established that the phylum Firmicutes exhibits a causal relationship with a reduced occurrence of coronary atherosclerosis. This investigation could potentially provide novel insights into therapeutic objectives for atherosclerosis by focusing on the gut microbiota.

Keywords

• coronary atherosclerosis
• cerebral atherosclerosis
• intestinal microbiota
• phylum firmicutes