Abstract

A wealth of both experimental and epidemiological data supports the occurrence of complex interactions between parasites of the genus Schistosoma and the gut microbiota of their vertebrate hosts. Moreover, increasing evidence shows that signals from the host gut flora might be involved in the immunological cascade that culminates with the formation of tissue granulomas underlaying the pathophysiology of schistosomiasis. In two recent studies we investigated the impact of experimental S. mansoni infections on the gut microbiome composition and metabolic capacity of mice colonised with gut microbial populations from a healthy human donor (HMA mice), as well as microbiota-wild type (WT) rodents. Our results showed significantly higher infection burdens in HMA compared to WT mice, which were linked to extensive dissimilarities between the gut microbial profiles of each mouse line at baseline. Infection-associated alterations of the gut microbiota composition also differed between the two mouse lines. However, remarkably, selected metabolic pathways were consistently affected by parasite infection in HMA and WT mice. In particular, the gut microbiomes of infected mice of both lines displayed enhanced capacity for tryptophan and butyrate production, which might be linked to the activation of mechanisms aimed at preventing excessive injuries caused by migrating parasite eggs. Thus, complementing data from previous studies, our findings suggest that the host gut microbiome might play a dual role in the pathophysiology of schistosomiasis, where intestinal bacteria may contribute to egg-associated pathology while, in turn, protect the host from uncontrolled tissue damage. Indeed, the immunomodulatory ability of the schistosome-associated microbiota is supported by our preliminary observation that faecal microbial transplants from S. mansoni-infected to germ free mice ameliorate allergic airway inflammation. Future investigations are necessary to identify specific bacteria-derived products mediating such protective effects. Thus far, studies undertaking this task have mainly focused on selected microbial metabolites (e.g., short chain fatty acids). However, recent advances in gut microbiome research point towards an important role for microbiota-derived extracellular vesicles in the regulation of both intestinal barrier function and host immunity; therefore, these nanoparticles might represent yet overlooked key mediators of host-helminth-microbiota crosstalk.

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