Parabacteroides distasonis-derived ursodeoxycholic acid alleviates macrophage foaming and atherosclerosis progression by targeting NLRP3

Atherosclerosis (AS) is a persistent immune-mediated inflammatory condition characterized by high morbidity and mortality rates. Ursodeoxycholic acid (UDCA) exhibits anti-inflammatory properties and the ability to reduce lipid levels. This study aimed to investigate the action and mechanisms of Parabacteroides distasonis ( P. distasonis )-derived UDCA on AS. The anti-atherosclerotic effect of UDCA in THP-1-derived macrophages exposed to oxidized low-density lipoprotein (ox-LDLs) was investigated using Oil red O staining, biochemical analyses, qRT-PCR, western blot, and ELISA in vitro . Also, apolipoprotein E knockout (ApoE −/− ) mice fed a high-fat diet (HFD) were established to investigate the anti-atherosclerotic effects of UDCA in vivo . UDCA suppressed macrophage foaming, M1 polarization, and ox-LDL-induced NLRP3 inflammasome activation in THP-1-derived macrophages. However, NLRP3 overexpression demonstrated an opposite effect and reversed the effect of UDCA in ox-LDL-induced THP-1 macrophages. Furthermore, P . distasonis alleviated the atherosclerotic lesion area, M1 polarization, and NLRP3 inflammasome activation in HFD-fed ApoE −/− mice. UDCA alleviated ox-LDL-triggered foam cell production, M1 polarization, and inflammatory response in macrophages derived from THP-1 cells through NLRP3 inhibition.