Lipid Species in the GI Tract are Increased by the Commensal Fungus Candida albicans and Decrease the Virulence of Clostridioides difficile

Abstract

<jats:p>Prior antibiotic treatment is a risk factor for Clostridioides difficile infection (CDI); the commensal gut microbiota plays a key role in determining host susceptibility to the disease. Previous studies demonstrate that the pre-colonization of mice with a commensal fungus, Candida albicans, protects against a lethal challenge with C. difficile spores. The results reported here demonstrate that the cecum contents of antibiotic-treated mice with C. albicans colonization contained different levels of several lipid species, including non-esterified, unsaturated long-chain fatty acids compared to non-C. albicans-colonized mice. Mice fed olive oil for one week and challenged with C. difficile spores showed enhanced survival compared to PBS-fed mice. The amount of olive oil administered was not sufficient to cause weight gain or to result in significant changes to the bacterial microbiota, in contrast to the effects of a high-fat diet. Furthermore, the direct exposure of C. difficile bacteria in laboratory culture to the unsaturated fatty acid oleic acid, the major fatty acid found in olive oil, reduced the transcription of genes encoding the toxins and reduced the survival of bacteria in the post-exponential phase. Therefore, the effects of C. albicans on the metabolite milieu contributed to the attenuation of C. difficile virulence.</jats:p>

Pre-colonization with the fungus Candida glabrata exacerbates infection by the bacterial pathogen Clostridioides difficile in a murine model

“…Total levels of bacteria were measured using qPCR and universal 16S rRNA primers as previously described ( 60 ). Relative abundance was multiplied by the total level of bacteria per milligram of cecum sample ( Fig.…”

“…While the contributions of commensal fungi during bacterial infections are not well understood, fungi have been implicated in a variety of polymicrobial interactions that could significantly impact host health ( 9 , 55 , 80 - 83 ) including those involving CDI ( 15 , 24 , 25 , 28 , 29 , 60 , 84 - 86 ). More recently, Santus and co-workers showed that Salmonella enterica can utilize commensal and dietary fungal siderophores which promote Salmonella colonization ( 87 ).…”

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

“…As a novel microbe colonizing the GI tract, C. albicans could have affected the bacterial microbiota through multiple physiological pathways. Previous researchers have characterized multiple changes in the immune environment of the gut in response to C. albicans colonization ( 35 , 36 ), and Romo et al demonstrated that C. albicans alters the metabolite milieu of the gut through increased abundance of nonesterified unsaturated fatty acids and other lipid species ( 37 ). In sum, our study adds to the body of work demonstrating that C. albicans , a fungus, mildly alters the composition of the bacterial microbiota in the context of the mouse GI tract environment.…”

The interplay between gut bacteria and the yeast Candida albicans

“…Another study found that the presence of C. albicans altered the levels of several lipid species in the mouse cecum, including non-esterified, unsaturated long-chain fatty acids. 83 Clearly, more comprehensive metabolome studies, ideally carried out in gnotobiotic animals, are needed to start delineating the metabolic footprint of the fungus in the intestine.…”