Abstract
Gut Microbiota (GM) dysbiosis associates with Atherosclerotic Cardiovascular Diseases (ACVD), but whether this also holds true in subjects without clinically manifest ACVD represents a challenge of personalized prevention. We connected exposure to diet (self-reported by food diaries) and markers of Subclinical Carotid Atherosclerosis (SCA) with individual taxonomic and functional GM profiles (from fecal metagenomic DNA) of 345 subjects without previous clinically manifest ACVD. Subjects without SCA reported consuming higher amounts of cereals, starchy vegetables, milky products, yoghurts and bakery products versus those with SCA (who reported to consume more mechanically separated meats). The variety of dietary sources significantly overlapped with the separations in GM composition between subjects without SCA and those with SCA (RV coefficient between nutrients quantities and microbial relative abundances at genus level = 0.65, p-value = 0.047). Additionally, specific bacterial species (Faecalibacterium prausnitzii in the absence of SCA and Escherichia coli in the presence of SCA) are directly related to over-representation of metagenomic pathways linked to different dietary sources (sulfur oxidation and starch degradation in absence of SCA, and metabolism of amino acids, syntheses of palmitate, choline, carnitines and Trimethylamine n-oxide in presence of SCA). These findings might contribute to hypothesize future strategies of personalized dietary intervention for primary CVD prevention setting.
Highlights
Atherosclerotic Cardiovascular Diseases (ACVD) still contribute significantly to excessive mortality, despite pharmacological weapons substantially improving their treatment [1]
Vs. +IMT/Subclinical Carotid Atherosclerosis (SCA), both on alpha (p = 0.001, permutation-based t-test on observed species metrics) and beta-diversity (p = 0.002, adonis test on Bray-Curtis distance) measures, this strategy allowed the identification of increased abundance of E. coli, as well as of members of the Streptococcus genus (i.e., S. salivarius, S. parasanguinis, S. anginosus) in metagenomes of subjects with +IMT/+SCA
The microbiome appears the most relevant potential target under this perspective, due to its involvement in the metabolism of dietary sources and since it is sensitive to rapid changes in dietary habits [7]
Summary
Atherosclerotic Cardiovascular Diseases (ACVD) still contribute significantly to excessive mortality, despite pharmacological weapons substantially improving their treatment [1]. The atherogenic properties of Trimethylamine n-oxide (TMAO), metabolized in the liver starting from dietary choline, have been deeply described [15,16,17,18,19,20] Despite these robust data, whether the individual exposure to different dietary sources relates with GM taxonomic alterations (namely, “dysbiosis”) even during initial stages of atherosclerosis and before clinical establishment of ACVD is still to be understood. Methodological criticisms affect GM composition analysis [24], the design of interventional dietary trials is scarce up to now, small-sized trials gave contrasting data about the effect of dietary intervention on changes of GM composition and subsequent effect on markers of ACVD risk [25] This sets the stage for an immediate clinical value, since the clustering of taxonomic and metagenomic signatures with individual dietary lifestyle might represent a pioneering approach of primary prevention, identifying patients among the population at increased risk of future occurrence of CVD.
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