Study On The Antagonistic Effect Of Koumiss On Mice Infected With Toxoplasma Gondii

Toxoplasma gondii is an important food-borne zoonotic parasite,and approximately one third of people worldwide are positive for T.gondii antibody.So far,there are no specific drugs and vaccines against T.gondii.Antibiotics are mainly used to treat clinical toxoplasmosis,yet which mostly have side effects and are ineffective in chronic T.gondii infection.Therefore,developing a new safe and effective way has become a new trend in treating toxoplasmosis.Koumiss has many functional components,modern medicine alleviates the clinical symptoms of many diseases by using the functional characteristics of koumiss and its regulation on intestinal flora.In order to explore the antagonistic effect of koumiss on T.gondii infection in BALB/c mice,this study established three models of acute infection,chronic infection and latent infection activation of T.gondii in mice.Mice were inoculated with 50 cysts of T.gondii PRU strain to establish a model of acute T.gondii infection.After infected with T.gondii,koumiss were fed by gavage daily and the survival rate,SHIRPA score,serum cytokines levels and intestinal flora changes were measured.The results showed that all mice were dead on 14 dpi and koumiss did not improve the survival rate of mice infected with acute T.gondii.However,after feeding koumiss,the clinical symptoms of mice were improved on 6 dpi and the SHIRPA score was decreased(P < 0.05).At the same time,the levels of IL-4,IFN-γ and TNF-α were decreased(P < 0.001,P < 0.001,P < 0.01).Moreover,the species composition of intestinal flora in mice were changed.The chronic T.gondii infection model in mice was established and koumiss were fed at the same time.The number of brain cysts,histopathological changes,β Amyloid deposition,serum cytokines levels and intestinal flora changes were measured to verify the effect of feeding koumiss.The results showed that koumiss could significantly reduce the number of brain cysts in mice(P < 0.05),relieve the infiltration of inflammatory reaction in brain tissue,improve β Amyloid deposition in hippocampus(P < 0.01)and down regulate the levels of IFN-γ and TNF-α(P < 0.01,P < 0.05).In addition,further study suggested that there were significant differences in the relative abundance of Lachnospiraceae and Akkermansia muciniphila(P < 0.05,P < 0.001)after feeding koumiss.Heat map analysis indicated that they had a close relation with specific pathways inhibiting T.gondii infection.BALB/c mice were inoculated with 3 cysts and dexamethasone(8 mg/L)was added into water at 28 dpi to establish a model of latent infection activation of T.gondii.Meanwhile,koumiss was fed by gavage every day.The results indicated the survival rate of mice was not increased after feeding koumiss.However,the clinical symptoms of mice were improved on 7dpi,the SHIRPA score was decreased(P < 0.05),and the parasite burden of T.gondii in brain,heart,liver and spleen was decreased significantly.In addition,the results showed that there were significant differences in the levels of IFN-γ and TNF-αand changes of the community structure of intestinal flora in experimental animals.This study demonstrated that koumiss had an significant effect on chronic T.gondii infection in mice and could improve the relevant indicators of acute T.gondii infection and latent infection activation of T.gondii in mice.The research provided a new ideas for developing safe and effective anti-T.gondii methods,and broadened thoughts for utilization of koumiss.