Compelling evidence now indicates that gut microbiota can influence host cardiovascular health and disease, since modulation of gut microbiota composition and function may alter host profile in favorable/unfavorable fashion (1). In particular, evidence that high circulating levels of the microbiota-generated metabolite trimethyl-amine-N-oxide (TMAO) are linked to an increased risk of atherosclerosis and cardiovascular risk is now solid (2-3).
In a recent issue of Circulation Research, Brandsma et al, add new pieces to this intricate puzzle. Here the Authors show that transplantation of gut microbiota from Casp1-/- mice induces inflammation and atherosclerosis in antibiotic-treated Ldlr -/- mice fed with a high-fat cholesterol-rich diet, establishing a causal relationship between microbiota composition, inflammation and atherosclerosis independent of plasma lipids, gut integrity and TMAO levels (4).
This important and interesting work raises several questions for future research. Further investigations will be required to define the fingerprint of a “healthy” microbiota, and to identify microbial metabolites mediating the crosstalk between host and bacteria, to be used as novel biomarkers and/or potential pharmacological targets (5). Only few studies have provided so far a mechanistic link between specific bacterial species and the monitored phenotype.
Moreover, multiple discrepancies can still be noted when comparing major bacterial groups identified in different studies, raising reproducibility concerns, considering also that microbe-microbe interactions might represent an additional knowledge gap. Finally, confounding effects related to environment, comorbidities, treatments and “reverse” effects of microbiota on drug metabolism should be taken into account when translating such preclinical observations to the clinical arena.
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