Villarino Nicolas F, LeCleir Gary R, Denny Joshua E, Dearth Stephen P, Harding Christopher L, Sloan Sarah S, Gribble Jennifer L, Campagna Shawn R, Wilhelm Steven W, Schmidt Nathan W
Department of Microbiology, University of Tennessee, Knoxville, TN 37996;
Department of Microbiology, University of Tennessee, Knoxville, TN 37996; Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202;
Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2235-40. doi: 10.1073/pnas.1504887113. Epub 2016 Feb 8.
Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.
疟原虫感染导致的临床表现从无症状到严重疟疾不等，每年造成约100万人死亡。尽管给人类带来了如此巨大的损失，但决定疾病严重程度的因素仍知之甚少。在此，我们表明小鼠的肠道微生物群会影响疟疾的发病机制。来自不同商业供应商的基因相似的小鼠，其肠道细菌群落存在差异，在感染多种疟原虫物种后，它们的寄生虫负荷和死亡率有显著差异。接受来自“抗性”或“易感”小鼠盲肠内容物移植的无菌小鼠，分别具有低和高的寄生虫负荷，这表明肠道微生物群决定了疟疾的严重程度。抗性小鼠肠道菌群的差异包括乳酸杆菌和双歧杆菌的丰度增加。先用抗生素治疗易感小鼠，然后用这些细菌属制成的酸奶进行处理，其寄生虫负荷降低。与寄生虫负荷的差异一致，抗性小鼠与易感小鼠相比表现出更高的体液免疫反应。总体而言，这些结果确定肠道微生物群的组成是严重疟疾先前未被识别的风险因素，而调节肠道微生物群（如益生菌）是降低寄生虫负荷的潜在治疗方法。
