Atherosclerosis (AS) currently lacks fully effective treatments. This study investigated the natural compound hesperidin as a potential therapy. Apolipoprotein E knockout (ApoE−/−) mice were used as a model of atherosclerosis; we found that hesperidin treatment improved physiological and metabolic health, reduced plaque formation, and decreased systemic inflammation and oxidative stress. Hesperidin also reshaped gut microbiota, increasing beneficial bacteria (Verrucomicrobia and Bacteroidota) and significantly lowering fecal levels of branched-chain amino acids (BCAAs: valine, leucine, and isoleucine) by 27.4%, 50.1%, and 40.8%, respectively. These changes were linked to specific microbial shifts. We conclude that hesperidin alleviates atherosclerosis likely by modulating the gut microbiota–BCAA–host axis, identifying it as a promising dietary intervention or therapeutic agent.
Wang et al. (Sun,) studied this question.