Abstract

BackgroundThe multifaceted interactions between gastrointestinal (GI) helminth parasites, host gut microbiota and immune system are emerging as a key area of research within the field of host-parasite relationships. In spite of the plethora of data available on the impact that GI helminths exert on the composition of the gut microflora, whether alterations of microbial profiles are caused by direct parasite-bacteria interactions or, indirectly, by alterations of the GI environment (e.g. mucosal immunity) remains to be determined. Furthermore, no data is thus far available on the downstream roles that qualitative and quantitative changes in gut microbial composition play in the overall pathophysiology of parasite infection and disease.ResultsIn this study, we investigated the fluctuations in microbiota composition and local immune microenvironment of sheep vaccinated against, and experimentally infected with, the ‘brown stomach worm’ Teladorsagia circumcincta, a parasite of worldwide socio-economic significance. We compared the faecal microbial profiles of vaccinated and subsequently infected sheep with those obtained from groups of unvaccinated/infected and unvaccinated/uninfected animals. We show that alterations of gut microbial composition are associated mainly with parasite infection, and that this involves the expansion of populations of bacteria with known pro-inflammatory properties that may contribute to the immunopathology of helminth disease. Using novel quantitative approaches for the analysis of confocal microscopy-derived images, we also show that gastric tissue infiltration of T cells is driven by parasitic infection rather than anti-helminth vaccination.ConclusionsTeladorsagia circumcincta infection leads to an expansion of potentially pro-inflammatory gut microbial species and abomasal T cells. This data paves the way for future experiments aimed to determine the contribution of the gut flora to the pathophysiology of parasitic disease, with the ultimate aim to design and develop novel treatment/control strategies focused on preventing and/or restricting bacterial-mediated inflammation upon infection by GI helminths.DCvTgHLrMa4pPTvhPWGjhoVideo

Highlights

  • The multifaceted interactions between gastrointestinal (GI) helminth parasites, host gut microbiota and immune system are emerging as a key area of research within the field of host-parasite relationships

  • Vac/Tc+ sheep had, on average, 66% fewer T. circumcincta eggs per gram of faeces at the point of peak egg shedding than Adj/Tc+ sheep and mean cumulative faecal egg counts (FEC) values for each sheep (cFEC) and worm burdens at post mortem showed overall reductions of 30% and 50% in vaccinated versus adjuvant-inoculated sheep

  • Determining the impact that colonisation by GI helminth parasites exerts on the composition of the gut microbial flora of their vertebrate hosts is key to the identification of populations of bacteria that may play active roles in immune and/or pathophysiological mechanisms that contribute to the outcome of infection and disease; in turn, this new knowledge could be exploited for the development of novel treatment and/or control strategies against parasitic diseases based on the manipulation of the gut microbiota

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Summary

Introduction

The multifaceted interactions between gastrointestinal (GI) helminth parasites, host gut microbiota and immune system are emerging as a key area of research within the field of host-parasite relationships. [9,10,11,12,13,14,15,16]) This raises the question of whether parasite-associated qualitative and quantitative modifications in gut microbiota, and of its metabolism, may represent mechanisms by which helminths establish chronic infections [9]. Whether such modifications are caused by direct interactions of the microbial flora with helminth parasites and/or, indirectly, by changes in the mucosal immune environment, remains to be established. One host-parasite pair in which such investigations are possible is the sheepTeladorsagia system

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