Decreased Ecological Resistance of the Gut Microbiota in Response to Clindamycin Challenge in Mice Colonized with the Fungus Candida albicans

Abstract

The mammalian gut microbiota is a complex community of microorganisms which typically exhibits remarkable stability. As the gut microbiota has been shown to affect many aspects of host health, the molecular keys to developing and maintaining a “healthy” gut microbiota are highly sought after. Yet, the qualities that define a microbiota as healthy remain elusive. We used the ability to resist change in response to antibiotic disruption, a quality we refer to as ecological resistance, as a metric for the health of the bacterial microbiota. Using a mouse model, we found that colonization with the commensal fungus Candida albicans decreased the ecological resistance of the bacterial microbiota in response to the antibiotic clindamycin such that increased microbiota disruption was observed in C. albicans-colonized mice compared to that in uncolonized mice. C. albicans colonization resulted in decreased alpha diversity and small changes in abundance of bacterial genera prior to clindamycin challenge. Strikingly, co-occurrence network analysis demonstrated that C. albicans colonization resulted in sweeping changes to the co-occurrence network structure, including decreased modularity and centrality and increased density. Thus, C. albicans colonization resulted in changes to the bacterial microbiota community and reduced its ecological resistance. IMPORTANCE Candida albicans is the most common fungal member of the human gut microbiota, yet its ability to interact with and affect the bacterial gut microbiota is largely uncharacterized. Previous reports showed limited changes in microbiota composition as defined by bacterial species abundance as a consequence of C. albicans colonization. We also observed only a few bacterial genera that were significantly altered in abundance in C. albicans-colonized mice; however, C. albicans colonization significantly changed the structure of the bacterial microbiota co-occurrence network. Additionally, C. albicans colonization changed the response of the bacterial microbiota ecosystem to a clinically relevant perturbation, challenge with the antibiotic clindamycin.

Leaky gut biomarkers in casein- and gluten-rich diet fed rat model of autism

“…It is suggested that the strictly anaerobic bacterial populations which predominate in the gut in CL-treated rats ( Enterobacteriaceae) are responsible for the inhibition of C. albicans adhesion, colonization, and diffusion from the intestinal tract ( Table 3 ; Groups 2, 3, and 4). This explanation could be further supported through considering the most recent work of Markey et al [ 64 ], who reported that bacterial colonization and the C. albicans are more easily changed by CL treatment providing perception into the microbiota response to acute CL challenge and the effect of C. albicans colonization on ecological resistance.…”

The interplay between gut bacteria and the yeast Candida albicans

“… 20 , 21 The fungus also has a role in the ability of intestinal microbial consortia to resist change in response to antibiotic disruption, which is termed ecological resistance. 22 Furthermore, gut fungal dysbiosis has been associated with reduced efficacy in fecal transplants currently in use to treat recurrent Clostridium difficile infections. 23 …”

“…20,21 The fungus also has a role in the ability of intestinal microbial consortia to resist change in response to antibiotic disruption, which is termed ecological resistance. 22 Furthermore, gut fungal dysbiosis has been associated with reduced efficacy in fecal transplants currently in use to treat recurrent Clostridium difficile infections. 23 In a longitudinal study of a cohort of 178 preterm infants in which the assembly of the intestinal microbiota was monitored, Rao et al 24 were able to infer several interdependencies between specific fungi and bacterial taxa.…”