Modulating effects of the probiotic Lactococcus lactis on the hepatic fibrotic process induced by CCl₄ in Wistar rats

Hepatic cirrhosis is a chronic disease that affects one fifth of the World's population and is the third leading cause of death in Mexico. Attempts have been made to develop treatments for this hepatic cirrhosis, which include manipulating the intestinal microbiota and thus decreasing the early inflammatory response. The microbiota is reportedly altered in patients with cirrhosis. Due to its immunomodulatory properties and its ability to survive in the gastrointestinal tract, Lactococcus lactis (L. lactis) has been used as a therapeutic measure in inflammatory disorders of the colon. The objective of the present study was to evaluate the efficacy of the L. lactis probiotic NZ9000 in preventing tetrachloromethane (CCl₄)-induced experimental hepatic fibrosis. The following 4 groups were included in the experimental stage (n=5): i) Control group; ii) L. lactis group; iii) CCl₄ group; and iv) L. lactis-CCl₄ group. For the first 2 weeks, L. lactis was orally administered to the L. lactis and L. lactis-CCl₄ groups; CCl₄ was then peritoneally administered to the lactis-CCl₄ group for a further 4 weeks (in addition to the probiotic), while the L. lactis group received the probiotic only. For the CCl₄ group, CCl₄ was administered for 4 weeks. The experimental groups were all compared with the control group and the L. lactis + CCl₄ group. Tissue samples were analyzed histologically and biochemically, and the gene expression levels of interleukin (IL)-1, IL-10 and forkhead box protein P3 (FoxP3) were determined. L. lactis decreased hepatic cirrhosis by preventing steatosis and fibrosis, and by reducing the levels of AST and ALT. Subchronic CCl₄ injury induced upregulation of the IL-1β gene in the liver, which was decreased by L. lactis. It was also found that the group treated with L. lactis showed increased expression of Foxp3 in the liver and IL-10 in the gut. These results suggested that oral administration of L. lactis may be a potential probiotic to prevent or protect against CCl₄-induced liver injury.