The Anti-Inflammatory Effect of Lactococcus lactis-Ling-Zhi 8 on Ameliorating Atherosclerosis and Nonalcoholic Fatty Liver in High-Fat Diet Rabbits

Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant <i>Lactococcus lactis</i> strain expressing the Ling-Zhi immunomodulatory protein (<i>L. lactis</i>-LZ8). This study investigated the anti-atherosclerotic effects of <i>L. lactis</i>-LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of <i>L. lactis</i>-LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving <i>L. lactis</i>-LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the <i>L. lactis</i>-LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the <i>L. lactis</i>-LZ8 group. Our studies underscore LZ8's role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD.