<i>eIF6</i> deficiency regulates gut microbiota, decreases systemic inflammation, and alleviates atherosclerosis

Altered composition of the gut microbiota affects immunity and metabolism. This study previously found that <i>eIF6</i> gene knockdown changes the composition of the intestinal flora in the <i>eIF6</i> gene knockdown mouse model. <i>Lactobacillus acidophilus</i> is significantly increased in the model. This study was designed to investigate the role of <i>L. acidophilus</i> in the pathogenesis of atherosclerosis. Transcriptomic data from 117 patients with coronary artery disease (CAD) and 79 healthy individuals were obtained. <i>ApoE</i>^-/- and <i>ApoE</i>^-/-/<i>eIF6</i>^+/- mice on normal chow diet or a high-fat diet were treated for 16 weeks; <i>eIF6</i> deficiency was evaluated atherosclerosis. <i>ApoE</i>^-/- mice on normal chow diet or a high-fat diet were treated with <i>L. acidophilus</i> by daily oral gavage for 16 weeks. Moreover, one group was treated with lipopolysaccharide at 12 weeks. The levels of <i>eIF6</i>, <i>RNASE3</i>, and <i>RSAD2</i> were notably higher in the patients with CAD than in the healthy individuals. <i>eIF6</i> deficiency altered the composition of gut microbiota. <i>eIF6</i> deficiency reduced the atherosclerotic lesion formation in <i>ApoE</i>^-/-/<i>eIF6</i>^+/- mice compared with the <i>ApoE</i>^-/- mice. The microbial sequencing and metabolomics analysis demonstrated some beneficial bacterial (<i>L. acidophilus</i>, <i>Ileibacterium</i>, and <i>Bifidobacterium</i>) and metabolic levels significantly had deference in <i>ApoE</i>^-/-/<i>eIF6</i>^+/- mice compared with the <i>ApoE</i>^-/- mice. Correlational studies indicated that <i>L. acidophilus</i> had close correlations with low-density lipoprotein cholesterol, lesion area, and necrotic area. <i>L. acidophilus</i> inhibited high-fat diet-induced inflammation and atherosclerotic lesion, increasing the expression of tight junction proteins (ZO-1 and claudin-1) and reducing the gut permeability. However, lipopolysaccharide reversed the protective effect of <i>L. acidophilus</i> against atherosclerosis. <i>eIF6</i> deficiency protected against atherosclerosis by regulating the composition of gut microbiota and metabolites. <i>L. acidophilus</i> attenuated atherosclerotic lesions by reducing inflammation and increasing gut permeability.IMPORTANCE<i>eIF6</i> deficiency modulates the gut microbiota and multiple metabolites in atherosclerotic <i>ApoE</i>^<i>-/-</i> mice. <i>L. acidophilus</i> was reduced in the gut of atherosclerotic <i>ApoE</i>^<i>-/-</i> mice, but administration of <i>Lactobacillus acidophilus</i> reversed intestinal barrier dysfunction and vascular inflammation. Our findings suggest that targeting individual species is a beneficial therapeutic strategy to prevent inflammation and atherosclerosis.