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EXPERIMENTAL INFECTIONS WITH TWO DIFFERENT BLASTOCYSTIS SUBTYPES ARE ASSOCIATED WITH STRIKINGLY DIFFERENT MICROBIOME FEATURES AND PATHOBIOLOGICAL OUTCOMES (ID 688)
Abstract
Introduction
The associations between Blastocystis and gut microbiota have been extensively studied, but no study so far has examined the influence of different subtypes (STs) of Blastocystis on gut microbiota under experimentally controlled conditions. Furthermore, whether Blastocystis-altered gut microbiota affects the development of intestinal inflammatory diseases remains to be determined.
Methods
In this study, we first investigated the effect of ST4, a common subtype in Europe, and ST7, a rare pathogenic subtype in humans, on the intestinal microbiota in normal healthy mice, and then explored the role of Blastocystis-altered gut microbiome in the development of dextran sulfate sodium (DSS)-induced colitis in antibiotic treated wild type and Rag1-/- mice.
Results
We showed that ST4 infection increased the bacterial diversity and abundance of Clostridia, whereas ST7 infection showed opposite effects. Transplantation of ST4-altered microbiota was able to prevent DSS-induced colitis by enhancing the Treg response (increased Foxp3 and IL-10) in the colon lamina propria of recipient mice, while ST7-altered microbiota exacerbated the severity of the colitis by inducing Th1 cell differentiation (increased IFN-γ, and TNF-α). Furthermore, the protective or exacerbating effects of Blastocystis-altered gut microbiota on colitis are adaptive immune cell dependent.
Conclusions
Our data showed that ST4 and ST7 infections are associated with strikingly different microbiome features, and these alterations have significantly different effects on the severity of DSS-induced colitis. This study supports accumulating evidence that clinical outcomes of Blastocystis infection is subtype dependent.