Enhanced_susceptibility_to_schistosomiasis_in_mice_carrying_human_microbiome_-sc-6276
Enhanced_susceptibility_to_schistosomiasis_in_mice_carrying_human_microbiome_
n spite of the extensive contribution of hepato-intestinal pathology to the pathophysiology of schistosomiasis, little is known of the impact of schisosome infection on the composition of the gut microbiota of its mammalian host and vice versa.   In this project, we aim to profile the gut luminal microbiota of conventional and gut microbiota-humanised mice experimentally-infected with S. mansoni before and after the onset of egg laying, i.e. 28- and 50-days post-infection, and compare the findings with cohorts of uninfected mice. Preliminary 16S rRNA-amplicon sequencing data revealed that acute and chronic S. mansoni infections were associated with global shifts in the composition of the rodent gut microbiota; such shifts included significant changes in the abundance of selected bacterial taxa with likely roles in the pathophysiology of infection and disease. Strikingly, at the end of the experiment, significantly higher worm and egg burdens were observed in the gut microbiota-humanised mice compared to conventional mice. These data support a role of the mammalian gut microbiota in the pathogenesis of hepato-intestinal schistosomiasis, including infection establishment, and serves as a foundation for the design of mechanistic studies to unravel the complex relationships amongst parasitic helminths, gut microbiota, pathophysiology of infection and host immunity.  We now aim to subject gut luminal samples collected over the course of this experiment to whole shotgun metagenomic DNA sequencing. We aim to multiplex DNA preparations (32 samples in total) in a single lane of NovaSeq, 150PE.   This dataset will substantially increase the resolution of the previously generated 16S sRNA-amplicon sequencing data and, most importantly, will allow gene-based (rather than taxon-based) predictions of bacterial metabolic pathways with likely roles in the establishment of schistosome infection in the two different mouse strains. Ultimately, this dataset will represent a solid platform to build novel mechanistic hypotheses on the contribution of the gut microbiota composition and function on the establishment of schistosomes in the vertebrate hosts, hypotheses that we aim to functionally address in follow up studies.  This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Enhanced susceptibility to schistosomiasis in mice carrying human microbiome