Clostridium butyricum Ameliorates Atherosclerosis by Regulating Host Linoleic Acid Metabolism

Dysbiosis of the gut microbiota is strongly implicated in atherosclerosis (AS), thus prompting microbial modulation to be explored as a therapeutic strategy. However, limited evidence exists for probiotic interventions capable of alleviating AS. Here, we focused on <i>Clostridium butyricum</i> (<i>C. butyricum</i>; CB), a probiotic known for its production of short-chain fatty acids (SCFAs). We found that administration of <i>C. butyricum</i> to high-fat diet (HFD)-fed <i>Apoe</i> deficient (<i>Apoe^-/-</i>) mice reduced plaque area by improving blood lipid profiles, decreasing macrophage infiltration in the aortic roots, and lowering the levels of circulating pro-inflammatory monocytes and macrophages. By non-targeted serum metabolomics analysis, <i>C. butyricum</i> treatment significantly reduced the levels of both linoleic acid and its downstream metabolites. Collectively, these findings establish <i>C. butyricum</i>-mediated amelioration of AS through modulation of linoleic acid metabolism.