AUTHOR=Zhang Wenchuan , Zhang Shuwan , Zhao Feng , Du Jinda , Wang Zhe 

TITLE=Causal relationship between gut microbes and cardiovascular protein expression

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1048519

DOI=10.3389/fcimb.2022.1048519

ISSN=2235-2988

ABSTRACT=<p>Evidence supports associations between gut microbiota and cardiovascular protein levels in plasma. However, it is unclear whether these associations reflect a causal relationship. To reveal the causal relationship between gut microbiota and cardiovascular protein levels in plasma, we estimated their causal effects using two-sample Mendelian randomization (MR) analysis. Sensitivity analysis was also performed to assess the robustness of our results. Genome-wide association study (GWAS) of microbiomes in the MiBioGen study included 211 bacterial taxa (18,473 individuals), and GWAS of 90 cardiovascular proteins included 30,931 individuals. There were 196 bacterial taxa from five levels available for analysis. The following 14 causal relationships were identified: phylum <italic>Euryarchaeota</italic> and carbohydrate antigen 125 (β = 0.289), order <italic>Bacillales</italic> and CSF-1 (β = -0.211), genus <italic>Dorea</italic> and HSP-27 (β = 0.465), phylum <italic>Actinobacteria</italic> and IL-8 (β = 0.274), order <italic>Enterobacteriales</italic> and KIM-1 (β = -0.499), class <italic>Actinobacteria</italic>, genus <italic>Bifidobacterium</italic>, phylum <italic>Actinobacteria</italic> and LEP (β = -0.219, β = -0.201, and β = -0.221), genus <italic>Methanobrevibacter</italic> and NT-proBNP (β = 0.371), family <italic>Peptostreptococcaceae</italic> and SRC (β = 0.191), order <italic>Verrucomicrobiales</italic>, phylum <italic>Verrucomicrobia</italic> and TNF-R2 (β = 0.251 and β = 0.233), family <italic>Veillonellaceae</italic> and t-PA (β = 0.271), and class <italic>Erysipelotrichia</italic> and VEGF-D (β = 0.390). Sensitivity analysis showed no evidence of pleiotropy or heterogeneity. The results of the reverse MR analysis showed no reverse causality for any of the 13 gut microbes and 11 cardiovascular proteins. Mendelian randomization estimates provide strong evidence for a causal effect of gut microbiota-mediated alterations on cardiovascular protein expression.</p>