4.4 Article

Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans

期刊

MSPHERE
卷 1, 期 1, 页码 -

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/mSphere.00020-15

关键词

microbiome; commensal; pathogenesis; carbon metabolism; Candida; Candida albicans; host-pathogen interactions; medium-chain fatty acids; fatty acids

资金

  1. HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [R01AI081794]
  2. HHS \ NIH \ National Center for Research Resources (NCRR) [UL1RR025752]
  3. HHS \ NIH \ National Institute of General Medical Sciences (NIGMS) [K12GM074869]
  4. National Center for Advancing Translational Sciences, NIH [UL1TR000073, UL1TR001064]
  5. NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001064, UL1TR000073] Funding Source: NIH RePORTER
  6. NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025752] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI081794] Funding Source: NIH RePORTER
  8. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [K12GM074869] Funding Source: NIH RePORTER

向作者/读者索取更多资源

Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of similar to 40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal drugs prevents C. albicans- associated mortalities. C. albicans provides a clinically relevant system for studying the relationship between diet and the microbiota as it relates to commensalism and pathogenicity. As a first step toward a dietary intervention to reduce C. albicans GI colonization, we investigated the impact of dietary lipids on murine colonization by C. albicans. Coconut oil and its constituent fatty acids have antifungal activity in vitro; we hypothesized that dietary coconut oil would reduce GI colonization by C. albicans. Colonization was lower in mice fed a coconut oil-rich diet than in mice fed diets rich in beef tallow or soybean oil. Switching beef tallow-fed mice to a coconut oil diet reduced preexisting colonization. Coconut oil reduced colonization even when the diet also contained beef tallow. Dietary coconut oil also altered the metabolic program of colonizing C. albicans cells. Long-chain fatty acids were less abundant in the cecal contents of coconut oil-fed mice than in the cecal contents of beef tallow-fed mice; the expression of genes involved in fatty acid utilization was lower in C. albicans from coconut oil-fed mice than in C. albicans from beef tallow-fed mice. Extrapolating to humans, these findings suggest that coconut oil could become the first dietary intervention to reduce C. albicans GI colonization. IMPORTANCE Candida albicans, the most common human fungal pathogen, can cause infections with a mortality rate of similar to 40%. C. albicans is part of the normal gut flora, but when a patient's immune system is compromised, it can leave the gut and cause infections. By reducing the amount of C. albicans in the gut of susceptible patients, infections (and the resulting fatalities) can be prevented. Currently, this is done using antimicrobial drugs; to preserve drugs for treating infections, we looked for a dietary change to reduce the amount of C. albicans in the gut. Using a mouse model, we showed that adding coconut oil to the diet could become the first drug-free way to reduce C. albicans in the gut. More broadly, this model lets us study the interactions between our diet and the microbes in our body and the reasons why some of those microbes, under certain conditions, cause disease.

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