Mendelian randomization combined with real-world study reveals that Streptococcus anginosus exacerbates dietary triglyceride metabolism disorders in obese mice.

Mendelian Randomization (MR) analysis can link the host gut microbiome to cardiovascular diseases. Streptococcus anginosus (S. anginosus) has been found to be positively correlated with early atherosclerosis, but its role in lipid metabolism remains to be explored. To investigate the impact of S. anginosus on lipid metabolism, we employed M methods using large-scale population genome-wide association study (GWAS) sequencing data, combined with a C57BL/6J mouse obesity model to assess the role of S. anginosus in lipid metabolism. Throughout the entire experiment, we monitored the dynamic changes in serum blood lipids in mice and the abundance of S. anginosus in feces. We evaluated the accumulation of lipid droplets in the liver and adipose tissue, as well as examined the gene-level expression changes of lipid metabolism enzymes and transcription factors. The findings from MR analysis indicate that ten specific gut microbial taxa including Streptococcaceae exhibit a causal relationship with disorders of lipoprotein metabolism. Notably, Streptococcaceae has been identified as a risk factor for it. Furthermore, S. anginosus has been shown to elevate serum triglycerides (TG) levels, diminish the accumulation of lipid droplets in both hepatic and adipose tissues, and downregulate the gene expression of enzymes involved in TG synthesis and metabolism. These findings suggest that S. anginosus is a risk factor for lipoprotein disorders and reduces dietary lipid metabolism in a mouse obesity model, leading to TG metabolism dysfunction. This study combines bioinformatics analysis and animal experiments to provide new insights into S. anginosus as a risk factor for lipid metabolism disorders.