23 Nov 2020

Role of Schistosomiasis in dysbiosis, inflammation and bacterial translocation in children from Nigeria (Acronym: SiDIC study)

Duration:30 months
Project Value: €149,775

Coordinator: Dr Olumide Ajibola

Summary of the Project

Schistosoma infections are most prevalent and intense in children. Salmonella is another infection that can impact this population and it has similar modes of transmission as schistosomiasis, due to a lack of good hygiene practices, access to clean water, and poor health care facilities in affected countries. Since S. Typhi, the causative agent of typhoid fever is a human host-restricted pathogen a comprehensive understanding of the co-morbid risk factors associated with infection and bacterial shedding is critical for disease control. Schistosomiasis has been long recognized for establishing a symbiotic relationship with Salmonella, yet its contribution to the epidemiology of Salmonella and asymptomatic shedding is unknown. There is evidence to demonstrate that schistosomiasis infection modulates the gut microbiome causing dysbiosis and a bloom in Proteobacteria.

Based on this evidence, I aim to determine the impact of Schistosoma infection on the gut microbiome, gut barrier function and Salmonella translocation. To achieve this aim, this study will carry out three objectives (i) Characterise the microbiome and gut barrier function of Schistosoma, Salmonella and Schistosoma-Salmonella co-morbid infections in Nigerian children (ii) Evaluate the temporal changes in microbiome structure after praziquantel administration (iii) Determine the impact of S. haematobium-infected microbiome on Salmonella colonization and shedding by utilizing fecal microbiome transplant mice models.

In the first objective, a hospital-based surveillance for, mono and coinfections of Schistosoma-Salmonella patients will be carried out, and blood, stool and urine profiled to investigate gut dysbiosis and elevation of gut inflammation markers. Second, to demonstrate that S. haematobium indeed impacts the microbiome and is associated with dysbiosis in the gut, a one-year longitudinal survey on children identified to be infected with schistosomiasis, and treated, will be carried out to determine the impacts of treatment on the restoration of the gut microbiome to homeostasis. Third, to validate that S. haematobium induced inflammation promotes bacterial translocation, germ free mice will be used for fecal microbiome transplant of S. haematobium infected versus uninfected children to assess susceptibility of the mice to S. enterica infections.

Together, the proposed work here will provide important information on the burden of coinfections of Schistosoma and Salmonella among children and the role of the parasite as a risk factor for bacteremia. The findings could encourage the inclusion of screening for schistosomiasis in the clinical diagnosis algorithm for children that are bacteremic, in order to improve their standard of care, recovery,and disease control.