Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogenCandida albicans

Abstract

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.

Unveiling Candida albicans intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response

“…All of these bacteria are short-chain fatty acid (SCFA) producers, but the concentration and type of SCFA varied greatly between the species ( Figure 3a ). In agreement with a previous study, 18 B. adolescentis was the largest producer of SCFA, especially acetate, whereas R. intestinalis was the species that produced the largest amount of butyrate, with an average of 42.5 mM ( Figure 3a ). However, except for B. adolescentis , none of the supernatants of the tested species were able to inhibit C. albicans growth in vitro ( Figure 3b ).…”

“…We used Bifidobacterium adolescentis , strain L2–32 as a C. albicans inhibition control, since this strain has been recently shown to have a strong inhibitory effect on both C. albicans growth and morphology. 18 …”

Impact of Changes at the Candida Albicans Cell Surface Upon Immunogenicity and Colonisation in the Gastrointestinal Tract

“…B. thetaiotaomicron B5482 (DSM 2079) (Russell et al, 2013), B. adolescentis L2-32 (Barcenilla et al, 2000) and C. eutactus ART55/1 (Alessi et al, 2020) were obtained from strain collections at the Rowett Institute, University of Aberdeen, UK, and grown in anaerobic M2GSC medium (Miyazaki et al, 1997) at 37 • C overnight (Ricci et al, 2021). Note that B. thetaiotaomicron B5482 (DSM 2079) is the same strain as VPI-5482, which was used previously to examine mannan degradation (Cuskin et al, 2015).…”

“…To generate culture supernatants from B. thetaiotaomicron B5482 (DSM 2079), B. adolescentis L2-32 and C. eutactus ART55/1, each organism was cultured in anaerobic Hungate tubes containing M2GSC medium with 30 % clarified bovine rumen fluid and incubated at 37 • C overnight (Miyazaki et al, 1997;Ricci et al, 2021). Cultures were then centrifuged at 658 × g for 10 min and the supernatants sterilised by passage through 0.2 μm syringe-driven filter units (Millex, Merck Millipore ltd, Cork, Ireland) (Ricci et al, 2021).…”

“…Host-generated mucins and bile acids provide additional protection by suppressing C. albicans virulence traits (Kavanaugh et al, 2014;Guinan et al, 2019). Meanwhile, the gut microbiota limits the outgrowth of C. albicans via colonisation resistance, a phenomenon that includes the manipulation of gut pH and oxygen levels (Ubeda et al, 2010;Lawley and Walker, 2013;d'Enfert et al, 2021), as well as competition for nutrients and the generation of inhibitory metabolites such as short chain fatty acids (SCFAs) (Cummings, 1981;Kennedy and Volz, 1985a;Louis et al, 2007;Guinan et al, 2019;Ricci et al, 2021). For example, the SCFAs acetate, propionate and butyrate inhibit the growth and morphogenesis of C. albicans in vitro (Cottier et al, 2015;Cottier et al, 2017;Noverr and Huffnagle, 2004).…”