Abstract Body (Do not enter title and authors here): Introduction: Alloprevotella (Allo) represents a commensal microbiota in the gut of healthy people, whereas it is depleted in the sets of various metabolic disorders. Although the reduction of Allo has been associated with a heightened cardiovascular risk, its causal role has not yet been studied. Interestingly, our previous study revealed that Allo was negatively associated with atherosclerotic burden in Apolipoprotein E-deficient (ApoE-/-) mice, suggesting a potential protective role in atherogenesis.
Research Questions: We speculated that Allo may be a potential probiotic protecting against the progression of atherosclerosis.
Goals: To explore the influence of Allo on atherogenesis and its underlying molecular mechanisms.
Methods: A real-time qPCR was performed to identify the fecal abundance of A.rava in patients with atherosclerosis and healthy individuals. Five-week-old male ApoE-/- mice fed a Western diet (WD) were daily gavaged with live or heat-killed (HK) Alloprevotella Rava (A. rava) strain, or vehicle for 8 weeks. Parameters of systemic metabolism and atherosclerosis were evaluated. Fecal metagenome was employed to determine the alteration of gut microbial community and plasma untargeted metabolome was conducted to explore the impact of host metabolism among groups.
Results: We found that A.rava was robustly decreased in atherosclerotic patients. Importantly, either administration of live or HK A.rava was sufficient to reduce gut permeability, improve lipid metabolic homeostasis, and ameliorate atherosclerosis in ApoE-/- mice, whereas live A.rava exhibited more pronouncing athero-protective effects. Moreover, live A.rava treatment partially normalized the WD-induced gut microbiota dysbiosis. Of note, nor-deoxycholic acid (norDCA), a secondary bile acid, was prominently reduced in mice fed a Western diet, while it was largely reversed following live A.rava treatment. Interestingly, the plasma levels of norDCA were negatively associated with the severity of atherosclerosis. In addition, supplementation of norDCA was demonstrated to alleviate the progression of atherosclerosis, probably attributable to the inhibition of foam cell formation in a FABP4-dependent manner.
Conclusions: Our study revealed that A. rava may attenuate atherosclerosis through modulating norDCA transformation, making it a promising probiotic to prevent and treat for atherosclerosis.