Baseline Gut Microbiota Composition Is Associated With Schistosoma mansoni Infection Burden in Rodent Models.

Alba Cortés,Alexandre Almeida,Catherine Mccarthy,Charlotte Tolley,James Rooney,Trevor Lawley,Gabriel Rinaldi,Cordelia Brandt,Katherine Harcourt,Simon Clare,Matthew Berriman,Alice Costain,Andrew S Macdonald,Cinzia Cantacessi

doi:10.3389/fimmu.2020.593838

Abstract

In spite of growing evidence supporting the occurrence of complex interactions between Schistosoma and gut bacteria in mice and humans, no data is yet available on whether worm-mediated changes in microbiota composition are dependent on the baseline gut microbial profile of the vertebrate host. In addition, the impact of such changes on the susceptibility to, and pathophysiology of, schistosomiasis remains largely unexplored. In this study, mice colonized with gut microbial populations from a human donor (HMA mice), as well as microbiota-wild type (WT) animals, were infected with Schistosoma mansoni, and alterations of their gut microbial profiles at 50 days post-infection were compared to those occurring in uninfected HMA and WT rodents, respectively. Significantly higher worm and egg burdens, together with increased specific antibody responses to parasite antigens, were observed in HMA compared to WT mice. These differences were associated to extensive dissimilarities between the gut microbial profiles of each HMA and WT groups of mice at baseline; in particular, the gut microbiota of HMA animals was characterized by low microbial alpha diversity and expanded Proteobacteria, as well as by the absence of putative immunomodulatory bacteria (e.g. Lactobacillus). Furthermore, differences in infection-associated changes in gut microbiota composition were observed between HMA and WT mice. Altogether, our findings support the hypothesis that susceptibility to S. mansoni infection in mice is partially dependent on the composition of the host baseline microbiota. Moreover, this study highlights the applicability of HMA mouse models to address key biological questions on host-parasite-microbiota relationships in human helminthiases.

Highlights

The study of the interactions between the resident microbiota of the vertebrate gut and both enteric and non-enteric parasitic worms is emerging as a key area of research [1,2,3]
All human microbiota-associated (HMA) mice of both experimental batches were successfully infected with S. mansoni, whereas no adult worms or eggs were recovered from two Exposed to Schistosoma mansoni cercariae (Sm-exp) wild type (WT) animals included in the second experiment at post mortem; the latter were removed from subsequent analyses (Table 1)
The higher infection burdens observed in HMA compared to WT mice were accompanied by significantly higher levels of Schistosoma-specific antibodies in sera from HMA animals (Supplementary Figures 1 and 2)

Summary

Introduction

The study of the interactions between the resident microbiota of the vertebrate gut and both enteric and non-enteric parasitic worms is emerging as a key area of research [1,2,3]. Over the last decade, several studies performed under both experimental and natural conditions of parasite infections, have provided evidence of quantitative and qualitative changes in populations of gut and/or fecal bacterial communities associated with worm establishment [4, 5]. Some of these studies have shown that infection-associated alterations of the host gut microbiota impact on the pathogenesis and pathophysiology of helminthiases, e.g. via changes to worm burdens [6] and effects on parasite immune-modulatory properties [6,7,8,9]. Such knowledge will assist the development of intervention strategies for parasite control, and/or of novel therapeutics for the prevention and treatment of chronic inflammatory diseases, based on the rational manipulation of the host gut microbiota [12]

Methods

Results

Discussion

Conclusion