Colonization with two different <i>Blastocystis</i> subtypes in DSS-induced colitis mice is associated with strikingly different microbiome and pathological features

Abstract

<b>Rationale:</b> The gut microbiota plays a significant role in the pathogenesis of inflammatory bowel disease (IBD). However, the role of <i>Blastocystis</i> infection and <i>Blastocystis</i>-altered gut microbiota in the development of inflammatory diseases and their underlying mechanisms are not well understood. <b>Methods:</b> We investigated the effect of <i>Blastocystis</i> ST4 and ST7 infection on the intestinal microbiota, metabolism, and host immune responses, and then explored the role of <i>Blastocystis</i>-altered gut microbiome in the development of dextran sulfate sodium (DSS)-induced colitis in mice. <b>Results:</b> This study showed that prior colonization with ST4 conferred protection from DSS-induced colitis through elevating the abundance of beneficial bacteria, short-chain fatty acid (SCFA) production and the proportion of Foxp3⁺ and IL-10-producing CD4⁺ T cells. Conversely, prior ST7 infection exacerbated the severity of colitis by increasing the proportion of pathogenic bacteria and inducing pro-inflammatory IL-17A and TNF-α-producing CD4⁺ T cells. Furthermore, transplantation of ST4- and ST7-altered microbiota resulted in similar phenotypes. <b>Conclusions:</b> Our data showed that ST4 and ST7 infection exert strikingly differential effects on the gut microbiota, and these could influence the susceptibility to colitis. ST4 colonization prevented DSS-induced colitis in mice and may be considered as a novel therapeutic strategy against immunological diseases in the future, while ST7 infection is a potential risk factor for the development of experimentally induced colitis that warrants attention.