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

Jesus A Romo¹, Laura Markey², Carol A Kumamoto¹

¹Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA.

Journal of Fungi (Basel, Switzerland)

|July 9, 2020

Abstract:

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.

Insights

Commensal fungus Candida albicans colonization alters gut lipids, protecting against Clostridioides difficile infection (CDI). Unsaturated fatty acids, like oleic acid, reduce CDI virulence and enhance host survival.

Area of Science:

Microbiology
Immunology
Gastroenterology

Background:

Antibiotic treatment increases risk for Clostridioides difficile infection (CDI).
Gut microbiota composition influences host susceptibility to CDI.
Commensal fungus Candida albicans colonization protects mice against lethal C. difficile challenge.

Purpose of the Study:

To investigate the mechanisms by which Candida albicans colonization protects against C. difficile infection.
To identify specific metabolites altered by C. albicans colonization that affect C. difficile virulence.

Main Methods:

Analysis of cecum contents from antibiotic-treated mice colonized with C. albicans versus non-colonized controls.
Assessment of survival rates in mice fed olive oil or PBS and challenged with C. difficile spores.
In vitro exposure of C. difficile to oleic acid to evaluate toxin gene expression and bacterial survival.

Main Results:

Cecum contents of C. albicans-colonized mice showed altered levels of unsaturated long-chain fatty acids.
Olive oil feeding enhanced survival against C. difficile challenge without altering bacterial microbiota.
Oleic acid exposure reduced C. difficile toxin gene transcription and post-exponential phase survival.

Conclusions:

Candida albicans colonization modifies the gut metabolite milieu, including unsaturated fatty acids.
Unsaturated fatty acids, such as oleic acid, can directly attenuate C. difficile virulence.
These findings suggest a mechanism for fungal-mediated protection against bacterial infections by altering host metabolism.

Read full analysis

Keywords:

Candida albicans Clostridioides difficile colonization non-esterified fatty acids susceptibility

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