Modulation of bacterial re-colonization and host mucosal response during broad spectrum antibiotic recovery by the yeast <italic>Candida albicans</italic>.

Abstract

<italic>Candida albicans</italic> is an opportunistic fungal pathogen that remains a significant cause of human morbidity and mortality. This ubiquitous yeast is able to colonize diverse mucosal surfaces, including the oral cavity, gastrointestinal (GI) tract, and vaginal tract, but is considered to be a commensal in healthy individuals. Recent research has implicated alterations in the microbiota in initiating or exacerbating multiple mucosal diseases, and may increase the risk of systemic <italic>Candida</italic> infections. While <italic>Candida</italic> species are normal members of the human GI microbiota, little is known about its ability to modify the bacterial community structure. Previous studies have shown a number of culturable bacteria demonstrate antagonism towards <italic>C. albicans</italic> morphogenesis <italic>in vitro </italic>, however the unculturable nature of the microbiota has prevented further studies. We hypothesized that the effect of <italic>C. albicans</italic> colonization in the murine GI tract, during re-colonization dynamics following broad-spectrum antibiotic treatment, would result in alterations in the bacterial microbiota and host mucosal response. To investigate this, we utilized Terminal Restriction Fragment Length Polymorphism (T-RFLP) and clone libraries to study the unculturable GI bacteria following dysbiosis (<italic>C. albicans CHN1 </italic> and <italic>SC5314</italic> colonization during cefoperazone treatment). Following dysbiosis, <italic>CHN1</italic> is able to stably colonize the GI tract of mice long-term. This colonization resulted in ulcerations at the limiting ridge, but no other overt inflammation. Despite this lack of apparent histological inflammation, there was significantly elevated IL-17a and IL-13 expression in the mesenteric lymph nodes (MLN). The long-term presence of <italic>CHN1</italic>, following dysbiosis, resulted in an altered Lactic Acid Bacteria (LAB) population: from predominantly <italic>Lactobacillus</italic> to <italic>Enterococcus</italic>. To investigate the role of <italic>C. albicans </italic> in the absence of the indigenous microbiota, germfree mice were mono-associated with <italic>C. albicans</italic>. Colonized germfree mice had elevated <italic>C. albicans</italic> colonization, elevated ulcer occurrence, and elevated IL-4 and IL-13 expression in the MLN. These findings point towards a vital interaction between the microbiota and <italic>CHN1</italic> in shaping the microbial composition and inflammatory response in the GI tract.