| Summary: | <i>Blastocystis</i> is a common human intestinal protozoan parasite. Little is known about its prevalence in echinococcosis. This study tested whether <i>Echinococcus multilocularis</i> infection would increase host susceptibility to <i>Blastocystis</i>. A total of 114 fecal samples (68 hydatid disease patients and 46 healthy people) were collected from Tibetans in the Qinghai province in China. The presence of <i>Blastocystis</i> was identified by sequencing of the small subunit (SSU) rRNA gene. Balb/c mice were co-infected with <i>Blastocystis</i> and <i>E. multilocularis</i> and tested for host susceptibility to <i>Blastocystis</i>. The overall <i>Blastocystis</i> prevalence was 12.3%; 16.2% in the patients and 4.4% in healthy people (<i>p</i> < 0.05). Sequence analysis identified three known <i>Blastocystis</i> genotypes, including ST1, ST2, and ST3, and one unknown genotype. Experimental dual infection significantly reduced mouse survival rate (20%), induced more severe signs, and increased intestinal damages with a higher intestinal colonization level of <i>Blastocystis</i>. The mouse model showed that <i>E. multilocularis</i> infection increases host susceptibility to <i>Blastocystis</i>. Our study shows a significantly higher prevalence of <i>Blastocystis</i> in patients with liver echinococcosis and reveals that non-intestinal <i>E. multilocularis</i> infection increases host susceptibility to the <i>Blastocystis</i>. Our results highlight that <i>E. multilocularis</i> infection is associated with <i>Blastocystis</i>. These findings remind us that more attention should be paid to the gut health of the patients with a helminth infection during clinical patient care.
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