Gunsalus Kearney T W, Tornberg-Belanger Stephanie N, Matthan Nirupa R, Lichtenstein Alice H, Kumamoto Carol A
Training in Education and Critical Research Skills (TEACRS) Program, Tufts University, Boston, Massachusetts, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
mSphere. 2015 Nov 18;1(1). doi: 10.1128/mSphere.00020-15. eCollection 2016 Jan-Feb.
Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~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 ~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. Podcast: A podcast concerning this article is available.
白色念珠菌是最常见的人类真菌病原体，可引发全身感染，死亡率约为40%。感染源于胃肠道（GI）定植，白色念珠菌是正常微生物群的一部分。使用抗真菌药物减少高危患者的定植可预防白色念珠菌相关死亡。白色念珠菌为研究饮食与微生物群之间的关系（涉及共生和致病性）提供了一个临床相关系统。作为减少白色念珠菌胃肠道定植的饮食干预的第一步，我们研究了饮食脂质对白色念珠菌在小鼠体内定植的影响。椰子油及其组成脂肪酸在体外具有抗真菌活性；我们假设饮食中的椰子油会减少白色念珠菌在胃肠道的定植。喂食富含椰子油饮食的小鼠的定植率低于喂食富含牛脂或大豆油饮食的小鼠。将喂食牛脂的小鼠改为椰子油饮食可降低先前存在的定植率。即使饮食中也含有牛脂，椰子油仍能降低定植率。饮食中的椰子油还改变了定植的白色念珠菌细胞的代谢程序。喂食椰子油的小鼠盲肠内容物中的长链脂肪酸比喂食牛脂的小鼠盲肠内容物中的少；喂食椰子油的小鼠体内白色念珠菌中参与脂肪酸利用的基因表达低于喂食牛脂的小鼠体内白色念珠菌中的表达。推断到人类，这些发现表明椰子油可能成为减少白色念珠菌胃肠道定植的首个饮食干预措施。重要性白色念珠菌是最常见的人类真菌病原体，可导致死亡率约为40%的感染。白色念珠菌是正常肠道菌群的一部分，但当患者免疫系统受损时，它会离开肠道并引发感染。通过减少易感患者肠道内白色念珠菌的数量，可以预防感染（以及由此导致的死亡）。目前，这是通过使用抗菌药物来实现的；为了“保留”用于治疗感染的药物，我们寻找一种饮食改变来减少肠道内白色念珠菌的数量。使用小鼠模型，我们表明在饮食中添加椰子油可能成为减少肠道内白色念珠菌的首个无药物方法。更广泛地说，这个模型使我们能够研究饮食与体内微生物之间的相互作用，以及为什么其中一些微生物在某些条件下会引发疾病。播客：有关本文的播客可供收听。
