Assessment of relationships between faecal yeast overgrowth and yeast species, protozoan parasites, and bacterial population dynamics: a Dutch retrospective, single-centre, cohort study

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Background Yeast overgrowth in the human intestine is common, but its pathogenesis remains underexplored. In this study, we investigated the relationship between faecal yeast overgrowth and residing yeast species, protozoan parasites, and bacterial population dynamics. Methods In this Dutch single-centre observational cohort study, 2848 faecal samples from individuals undergoing parasitology exams were analysed for yeast growth by culture and species identification via CHROMagar and matrix-assisted laser desorption or ionisation time-of-flight mass spectrometry. Participants with 10 5 or more yeast colony-forming units (CFUs; overgrowth) without antibiotic exposure in the past 3 months were included and age-matched and sex-matched to participants without antibiotic exposure in the past 3 months who had no yeast growth or had less than 10 5 yeast CFU (ie, normal or elevated yeast growth) in a 1:1:1 ratio, to identify changes in fungal, parasitic, and bacterial microbiota associated with intestinal yeast overgrowth. Parasitological diagnosis was performed with microscopy and PCR. 16S bacterial microbiota sequencing was performed in a nested case–control study of 102 individuals. Samples from 78 healthy donors were used to establish normal yeast growth thresholds. In-vitro cultures of Blastocystis spp and Candida were used to study the effects of oxygen on growth. Findings Faecal samples were collected between 2015 and 2020. Of the 2848 samples, yeasts were isolated in 1855 (65·1%). Yeast growth varied markedly among individuals: normal growth (1–7300 CFU/g; 1440 [50·6%]), elevated growth (7301–10 5 CFU/g; 297 [10·4%]), and yeast overgrowth (>10 5 CFU/g; 118 [4·1%]). Yeast overgrowth was linked to antibiotic use in the 3 months before sample collection (p<0·0001) and proton-pump inhibitor use (p=0·0001). Candida albicans (87 [76%] of 115 of participants) and Candida glabrata (38 [33%] of 115) were the most common in yeast overgrowth. Compared with normal growth, prevalence of C glabrata rose significantly (from 2% to 33%, p<0·001), whereas that of Candida parapsilosis declined (from 10% to 2%, p<0·001). Overgrowth was associated with reduced prevalence of Dientamoeba fragilis (from 14% to 5%, p=0·0055) and Blastocystis spp (from 26% to 14%, p=0·0062). Bacterial alpha diversity declined (p=0·027) as the abundance of obligate anaerobes decreased. In vitro, C albicans growth was absent under strict anaerobic conditions but thrived in oxygen-rich environments, whereas Blastocystis grew abundantly in anaerobic conditions and was inhibited in the presence of oxygen. Interpretation Yeast overgrowth is associated with increased prevalence of C albicans and C glabrata , decreased prevalence of C parapsilosis , a marked reduction in the obligate anaerobic parasites D fragilis and Blastocystis spp, and a shift from anaerobic to facultative anaerobic bacteria. Elevated colonic luminal oxygen can drive these disturbances. These findings underscore the importance of understanding colonic oxygen regulation and its associated microbiota changes. Funding Netherlands Organization for Scientific Research; Amsterdam UMC; National Centre for Advancing Translational Sciences, National Institutes of Health.