Schistosoma mansoni infection is associated with quantitative and qualitative modifications of the mammalian intestinal microbiota

Timothy P Jenkins,Laura E Peachey,Michael H Hsieh,Andrew S Macdonald,Gabriel Rinaldi,Cinzia Cantacessi,Paul J Brindley,Nadim J Ajami

doi:10.1038/s41598-018-30412-x

Abstract

In spite of the extensive contribution of intestinal pathology to the pathophysiology of schistosomiasis, little is known of the impact of schistosome infection on the composition of the gut microbiota of its mammalian host. Here, we characterised the fluctuations in the composition of the gut microbial flora of the small and large intestine, as well as the changes in abundance of individual microbial species, of mice experimentally infected with Schistosoma mansoni with the goal of identifying microbial taxa with potential roles in the pathophysiology of infection and disease. Bioinformatic analyses of bacterial 16S rRNA gene data revealed an overall reduction in gut microbial alpha diversity, alongside a significant increase in microbial beta diversity characterised by expanded populations of Akkermansia muciniphila (phylum Verrucomicrobia) and lactobacilli, in the gut microbiota of S. mansoni-infected mice when compared to uninfected control animals. These data support a role of the mammalian gut microbiota in the pathogenesis of hepato-intestinal schistosomiasis 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.

Highlights

Schistosomiasis, a major neglected tropical disease, is considered the most problematic of the human helminthiases in terms of morbidity and mortality[1]
Granuloma formation is mediated by host immunity to egg antigens; in particular, while a strongly polarised Th2-mediated immune response is responsible for the development of large granulomas during the initial phases of parasite establishment, chronic infections are accompanied by the onset of regulatory responses that lead to the formation of smaller granulomas around newly deposited eggs[7]
An average of 40 mixed-sex adult parasites were recovered from individual S+ mice at D28 p.i., with comparable numbers being collected at D50 p.i

Summary

Introduction

Schistosomiasis, a major neglected tropical disease, is considered the most problematic of the human helminthiases in terms of morbidity and mortality[1]. The adult worms, which exhibit sexual dimorphism, migrate into the mesenteries of the intestines (S. japonicum and S. mansoni) or the blood vessels of the urinary bladder and other pelvic organs (S. haematobium), where they commence sexual reproduction releasing hundreds to thousands of eggs per day, depending on the species These parasites can live for decades[3,6]. Infection of SFB-deficient mice results in unaltered IL-17 gene expression[12], thereby supporting a key role for selected taxa of bacteria in helminth-driven modulation of immunity Based on these observations, it seems plausible to hypothesise that the shift between Th2-type and regulatory responses that accompany egg production and characterises chronic schistosomiasis may be triggered, at least in part and directly or indirectly, by parasite-associated modifications in the composition of the intestinal commensal microbiota. We have directly addressed this issue by defining qualitative and quantitative fluctuations in intestinal microbial community profiles during infection with S. mansoni, and identified groups of bacteria with known roles in immune-modulation (e.g. lactobacilli), maintenance of epithelial barrier function integrity (i.e. Akkermansia muciniphila), and intestinal inflammation (e.g. Dorea and Bacteroides acidifaciens) that may play significant roles in the pathophysiology of acute and chronic schistosomiasis

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Results

Conclusion