Authors

A O Kildemoes³; G Schramm²; B Pakkenberg¹; A M Jensen³; D S Nielsen³; S Skov³; A K Hansen³; B J Vennervald³;  ¹ Bispebjerg University Hospital, Denmark;  ² Research Center Borstel, Germany;  ³ University of Copenhagen, Denmark

Discussion

Chronic infection with the parasitic blood fluke, Schistosoma mansoni, present the most severe pathology related to egg-induced host immune responses and fibrosis development. Commensal gut microbial composition influences host immune homeostasis and hence potentially affects systemic immunopathology induced by pathogens such as S. mansoni. Both humans and experimental models show metabonomic changes related to gut microbial and liver metabolism associated with S. mansoni infection. These points towards a role for gut microbiota in S. mansoni pathology regulation via the host immune response. To investigate whether different gut microbial compositions would result in differences in pathology induced by S. mansoni eggs, a controlled mouse model combining antibiotics treatment and infection was established. The commensal gut microbial composition was altered by oral administration of ampicillin/vancomycin and combined with subsequent S. mansoni infection in a C57BL/6-NTAC mouse model. Here egg-induced hepatomegaly and relative degree of inflammation were quantified in liver and ileum tissues by stereological principles. A significantly lesser degree of inflammation in liver tissue in the combined antibiotics treated and S. mansoni infected group compared to the infected only group was seen. This difference in degree of inflammation was not observed in ileum tissue and could not be explained by infection burden. Furthermore, differences in liver panel parameters, number of collagen depositions and cytokines (IFN-ɣ, IL-33) underscore an altered response to S. mansoni eggs in the liver when the gut microbial composition is strongly altered before infection. Our results implicate a role for intestinal immune milieu influenced by gut microbial composition in liver pathology development and hence morbidity. Further research is necessary to determine whether more subtle alterations of gut microbial compositions by factors such as diet, other infections, food-associated antibiotics or drugs facilitate a strong enough change in immune milieu to affect systemic pathology.