Short-chain fatty acids (SCFAs) are important anti-inflammatory metabolites of intestinal flora. Oxidized low-density lipoprotein (ox-LDL)-induced macrophage activation is critical for the formation of atherosclerosis plaque. However, the association between SCFAs and ox-LDL-induced macrophage activation with respect to the formation of atherosclerosis plaque has not yet been elucidated. The present study investigated whether SCFAs (sodium acetate, sodium propionate, and sodium butyrate) can affect ox-LDL-induced macrophage activation and potential signaling pathways via regulation of the expression of the NLRP3/Caspase-1 pathway. Using human monocyte-macrophage (THP-1) cells as a model system, it was observed that ox-LDL not only induced cell inflammatory injury but also activated the NLRP3/Caspase-1 pathway. The exogenous supplementation of three SCFAs could significantly inhibit cell inflammatory injury induced by ox-LDL. Moreover, three SCFAs decreased the expression of IL-1β and TNF-α via the inactivation of the NLRP3/Caspase-1 pathway induced by ox-LDL. Furthermore, three SCFAs affected cellular metabolism in ox-LDL-induced macrophages, as detected by untargeted metabolomics analysis. The results of the present study indicated that three SCFAs inhibited ox-LDL-induced cell inflammatory injury by blocking the NLRP3/Caspase-1 pathway, thereby improving cellular metabolism. These findings may provide novel insights into the role of SCFA intervention in the progression of atherosclerotic plaque formation.

The overactivation of macrophages causes chronic inflammatory diseases. Short-chain fatty acids (SCFAs), potential drugs for clinical treatment, are modulators of macrophage inflammatory reaction. Therefore, the modulation of macrophage-mediated cell activity is expected to become a new therapeutic strategy for inflammatory diseases caused by Mycoplasma pneumoniae. In this study, 2 kinds of SCFAs (propionate and butyrate) were found to have anti-inflammatory effects in M. pneumoniae-stimulated THP-1 cells inflammatory. They inhibited the expressions of IL-4, IL-6, ROS, and NLRP3 inflammasome, while enhancing the expressions of IL-10 and IFN-γ. Our study revealed these 2 agents to repress transcriptional activities of NF-κB, which are important modulators of inflammation. Meanwhile, SCFAs can significantly enhance the autophagy induced by M. pneumoniae. Considering that SCFAs have few side effects, they might be the promising adjuvant therapy for the prevention and/or treatment of various inflammatory diseases.

In this study, we established a mouse colitis model using DSS to investigate the impact of curcumin on gut injury, the intestinal microbiota, and fecal metabolites. The findings indicated that curcumin effectively mitigated weight loss and colon shortening caused by colitis, enhanced the expression of anti-inflammatory factor IL-10 mRNA (p < 0.05), and suppressed the expression of pro-inflammatory factors (IL-1β, IL-6, and TNF-α mRNA; p < 0.05). 16S rDNA sequencing analysis showed that in the CUR group, compared to the NC and DSS groups, the abundances of Bacteroides, Lachnospiraceae NK4A136, and Ruminococcaceae UGC 014 significantly increased, while that of Lactobacillus markedly decreased. Additionally, compared with the DSS group, the CUR group demonstrated a significant decrease in levels of metabolites associated with nucleic acid and fat metabolism, including xanthosine, isocitric acid, and D-xylose. Conversely, levels of metabolites of curcumin, such as demethoxycurcumin and tetrahydrocurcumin, were significantly elevated in the CUR group. Curcumin appears to offer protection against mouse colitis by potentially enhancing the composition of the gut microbiota and regulating metabolic and inflammatory processes through its metabolites.