Composition and Functional Capacity of Gut Microbes are Associated with Arterial Stiffness: A Prospective Study

Abstract

Objective: Arterial stiffness is an important predictor of cardiovascular disease. Microbial diversity in the gut has been shown to be associated inversely with arterial stiffness in Caucasian populations. However, due to the different profiles of the gut microbiota among ethnicities, the relationship between gut-microbiota dysbiosis and the progression of arterial stiffness merits further investigation. This study aimed to investigate the association between the composition and functional capacity of the gut microbiota and the progression of arterial stiffness. Methods: “Shotgun” metagenomics sequencing were undertaken in 96 individuals from a hypertension-associated gut-microbiota study in the Kailuan cohort, who measured brachial-ankle pulse wave velocity (baPWV) and provided fecal samples between September 2014 and February 2015 at Kailuan General Hospital and 11 affiliated hospitals. The different composition and functional capacity of the gut microbiota were compared between individuals without arterial stiffness (normal arterial stiffness group, baPWV <1,400  cm/s, n = 27) and participants with arterial stiffness (increased arterial stiffness group, baPWV ≥1,400 cm/s, n = 69) at baseline. These participants were followed up prospectively for a mean duration of 2.6 years, and 50 underwent a repeat baPWV measurement. Associations between the gut microbiota and severity and progression of arterial stiffness were assessed using MaAsLin2 software after adjustment for age, sex, and mean arterial blood pressure and correction for multiple testing. Gene “catalogs” were aligned to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to obtain information for potential functional capacities of the gut microbiota. Results: In this study, 14 genera and 50 species of bacteria were identified to be abundant in participants with normal arterial stiffness compared with those with increased arterial stiffness. Of 14 genera, the prevalence of beneficial bacteria of the genera Leadbetterella and Cytophaga was correlated inversely with baPWV (P < 0.05). Analyses of functional capacity revealed gut-microbial dysfunctions in the synthetic processes of “threonine dehydratase” “hypothetical protein” “mannosyl transferase” and “type-IV secretion-system proteins” in individuals suffering from arterial stiffness. During follow-up, bacteria of the proinflammatory genera Escherichia, Shigella, and Ruegeria were enriched in individuals with increased baPWV. Functional analyses showed that 26 KEGG orthologs of gut microbes were associated with an increase in baPWV and involved in “carbohydrate metabolism” “amino acid metabolism” and “protein families related to genetic information processing.” Conclusions: The composition and functional capacity of the microbial community in the gut of people suffering from arterial stiffness differed from those in individuals not suffering from arterial stiffness. Our data provide a new direction for the causality of the host-gut microbiota in arterial stiffness.