Regulation of schistosomiasis by the host gut microbiome

<title>Abstract</title> <p> <bold>Background</bold> : Host responses to helminth infections, such as schistosomiasis, are influenced by genetic factors and the microbiome, which play crucial roles in shaping immune response. This study investigates the interplay between host genetics and the gut microbiome during chronic schistosomiasis. <bold>Results</bold> : Using two genetically different murine models (SPF1 C57BL/6 and SPF2 C57BL/6), with different susceptibility to chronic schistosomiasis, we found that the gut microbial profile is vital for the host resistance. Fecal microbiota transfer from the resistant SPF1 C57BL/6 strain to the susceptible SPF2 C57BL/6 strain reduced key pathological features and extended survival. In humans, shotgun metagenomics sequencing and qPCR analysis of stool DNA from school-aged children in <italic>S. mansoni</italic> -endemic areas revealed significant and consensual alterations in gut microbiome composition of schistosomiasis-affected individuals. Notably, we identified two gut bacterial species as reliable biomarkers of schistosomiasis: <italic>Bacteroides ovatus</italic> negatively associated with <italic>S. mansoni</italic> infection, and <italic>Turicibacter sanguinis</italic> correlated positively with liver fibrosis. Multi-omics integration analysis links these bacterial species to distinct altered metabolic pathways, especially the heavy solicitation by both of the purine metabolism and signaling pathway, aligning with the known dependence on the salvage pathway of the <italic>de novo</italic> synthesis of purines by schistosomes during the infection of human hosts. <bold>Conclusion</bold> Overall, our findings position the gut microbiome as both determinant of schistosomiasis outcomes and a promising source of biomarkers for the monitoring of infection and morbidity. </p>