New combination therapy of praziquantel and <i>Lactobacillus plantarum</i> for enhancing the treatment of clonorchiasis in mice.

Abstract

<i>Clonorchis sinensis</i>, a zoonotic trematode, parasitizes the bile ducts of humans and other mammals. It has been implicated in the development of liver fibrosis and cholangiocarcinoma. Currently, praziquantel is the sole drug for treating clonorchiasis, but it is not capable of reversing liver fibrosis. Therefore, it is critical to develop novel treatment strategies. Probiotics have garnered attention for their potential in treating a variety of intestinal infections, and they can influence the progression of liver diseases. In this study, a <i>C. sinensis</i>-induced liver fibrosis infection model was established in mice, with daily oral administration of <i>Lactobacillus plantarum</i> initiated immediately post-infection to investigate its anti-clonorchiasis effects. Body weight, survival time, liver/body weight ratio, parasite burden, liver lesions, and fibrosis were examined in <i>C. sinensis</i>-infected mice treated with or without <i>L. plantarum</i>. <i>L. plantarum</i> alleviated clonorchiasis in mice, as evidenced by mitigating weight loss, reducing the mortality rate by approximately 35.0%, decreasing the liver/body weight ratio, and reducing the parasite burden by 62.2%. <i>L. plantarum</i> also attenuated liver fibrosis in <i>C. sinensis</i>-infected mice, demonstrated by decreased collagen deposition and downregulated α-SMA expression. Furthermore, the synergistic effect of <i>L. plantarum</i> and praziquantel on treating clonorchiasis in mice was evaluated 35 d post-inoculation (dpi). When administered as monotherapy, praziquantel or <i>L. plantarum</i> reduced the hepatic parasite burden by 93.0% and 51.3%, respectively, resulting in a reduction of the liver fibrosis area from 21.8% to 12.2% and 9.0%, respectively. The combination of praziquantel and <i>L. plantarum</i> effectively eliminated almost all the hepatic parasites and further alleviated hepatic and biliary damage, resulting in an additional decrease in the liver fibrosis area to 6.0%. In summary, <i>L. plantarum</i> alleviated hepatic and biliary damage and liver fibrosis caused by <i>C. sinensis</i> in mice. The combination of <i>L. plantarum</i> and praziquantel showed enhanced efficacy in the treatment of clonorchiasis in mice, providing a potential novel strategy for a more effective treatment of <i>C. sinensis</i>-induced liver fibrosis.