The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via a process called colonisation resistance. Here, we investigated the antagonistic activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections in susceptible individuals. Co-culture batch incubations of C. albicans in the presence of faecal microbiota from six healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene amplicon profiling of these faecal co-culture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow up mechanistic studies performed under anaerobic conditions confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis, inhibited C. albicans in vitro. Fermentation acids, including acetate and lactate, present in the bifidobacterial supernatants were important contributors to inhibitory activity. However, increasing the pH of both bacterial supernatants and mixtures of fermentation acids reduced their anti-Candida effects, indicating a combinatorial effect of prevailing pH and fermentation acids. This work therefore demonstrates potential mechanisms underpinning gut microbiome-mediated colonisation resistance against C. albicans, and identifies particularly inhibitory components such as bifidobacteria and fermentation acids as targets for further study.
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Funding: Initial studies were funded from a Wellcome Institutional Strategic Support Fund (ISSF) Seed Corn Award [105625/Z/14/Z]. Thereafter, the research was funded by the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. AJPB was supported by programme grants from the UK Medical Research Council (MR/M026663/1; MR/M026663/2) and by the Medical Research Council Centre for Medical Mycology (MR/N006364/1; MR/N006364/2).
Acknowledgements: We thank Dr Donna M. MacCallum for critical reading of the manuscript, the Centre for Genome-Enabled Biology and Medicine at the University of Aberdeen for carrying out the 16S rRNA gene sequencing, and Donna Henderson for GC analysis of bacterial fermentation acids. The authors also acknowledge the support of the Maxwell computer cluster funded by the University of Aberdeen.
- Human gut microbiota
- colonisation resistance
- Candida albicans
- short chain fatty acids