Fungal-bacterial gut microbiota interactions in patients withClostridioides difficilecolonisation and infection

Abstract

AbstractObjectivesThe bacterial microbiota is well-recognised for its role inClostridioides difficilecolonisation and infection, while fungi and yeasts remain understudied. The aim of this study was to analyse the mycobiota and its interactions with the bacterial microbiota in light ofC. difficilecolonisation and infection.MethodsThe mycobiota was profiled by ITS2 sequencing of faecal DNA from infected patients (CDI; n = 29), asymptomatically colonised patients (CDC; n = 38) and hospitalised controls withC. difficilenegative stool culture (Controls; n = 38). Previously published 16S rRNA gene sequencing data of the same cohort were used additionally for machine learning and fungal-bacterial network analysis.ResultsCDI patients were characterised by a significantly higher abundance ofCandidaspp. (MD 0.270 ± 0.089,P= 0.002) andCandida albicans(MD 0.165 ± 0.082,P= 0.023) compared to Controls. Additionally, they were deprived ofAspergillusspp. (MD -0.067 ± 0.026,P= 0.000) andPenicilliumspp. (MD -0.118 ± 0.043,P= 0.000) compared to CDC patients. Network analysis revealed a positive association between several fungi and bacteria in CDI and CDC, although the analysis did not reveal a direct association betweenClostridioidesspp. and fungi. Furthermore, the microbiota machine learning model outperformed the models based on the mycobiota and the joint microbiota-mycobiota model. The microbiota classifier successfully distinguished CDI from CDC (AUROC = 0.884) and CDI from Controls (AUROC = 0.905).BlautiaandBifidobacteriumwere marker genera associated with CDC patients and Controls.ConclusionsThe gut mycobiota differs between CDI, CDC, and Controls, and may affectClostridioidesspp. through indirect interactions. The identification of bacterial marker genera associated with CDC and Controls warrants further investigation. Although the mycobiota’s predictive value ofC. difficilestatus was low, fungal-bacterial interactions might be considered when diagnosing and treatingC. difficileinfection.