Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model.
Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model.
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DOI：
10.1371/journal.pone.0131829
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Warren CA
中科院分区：
文献类型：
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作者：
Moore JH;Pinheiro CC;Zaenker EI;Bolick DT;Kolling GL;van Opstal E;Noronha FJ;De Medeiros PH;Rodriguez RS;Lima AA;Guerrant RL;Warren CA
艰难梭菌是抗生素相关性腹泻的主要可识别和可治疗的病因。营养不良会导致宿主对各种病原体的防御能力减弱，从而导致死亡。本研究的主要目的是评估在小鼠模型中减少蛋白质饮食对艰难梭菌感染结果的贡献。C57BL/6小鼠分别饲喂传统家鼠饲料或蛋白质含量为20%或2%的限定日粮，感染艰难梭菌VPI10463。监测动物的疾病严重程度、梭菌脱落和粪便毒素水平。研究人员测量了未处理或抗生素处理小鼠饲喂不同日粮的粪便中选定的肠道微生物群，并定量了肠道内容物中艰难梭菌的生长和毒素的产生。艰难梭菌感染的小鼠用特定的饮食喂养，特别是（出乎意料的）蛋白质缺乏饮食，增加了存活率，减轻了体重减轻，降低了总体疾病严重程度。感染后1 d，传统饮食组粪便中梭状芽孢杆菌的排出量和毒素均高于常规饮食组。与2%或20%的蛋白质营养饮食相比，传统饮食喂养的小鼠在抗生素暴露后肠道厚壁菌门与拟杆菌门的比例增加。体外接种经抗生素处理的小鼠盲肠内容物显示，与传统饮食相比，这两种饮食中毒素的产生和艰难梭菌的生长都有所减少。研究发现，低蛋白饮食和一般的营养饮食对小鼠的CDI有保护作用。与传统饮食相比，特定营养饮食中肠道微生物群的相关饮食诱导改变可能影响定植抗性和梭菌毒素的产生，从而提高生存率。然而，导致2%和20%蛋白质定义的营养饮食之间生存差异的机制需要进一步阐明。
Clostridium difficile is a major identifiable and treatable cause of antibiotic-associated diarrhea. Poor nutritional status contributes to mortality through weakened host defenses against various pathogens. The primary goal of this study was to assess the contribution of a reduced protein diet to the outcomes of C. difficile infection in a murine model. C57BL/6 mice were fed a traditional house chow or a defined diet with either 20% protein or 2% protein and infected with C. difficile strain VPI10463. Animals were monitored for disease severity, clostridial shedding and fecal toxin levels. Select intestinal microbiota were measured in stool and C. difficile growth and toxin production were quantified ex vivo in intestinal contents from untreated or antibiotic-treated mice fed with the different diets. C. difficile infected mice fed with defined diets, particularly (and unexpectedly) with protein deficient diet, had increased survival, decreased weight loss, and decreased overall disease severity. C. difficile shedding and toxin in the stool of the traditional diet group was increased compared with either defined diet 1 day post infection. Mice fed with traditional diet had an increased intestinal Firmicutes to Bacteroidetes ratio following antibiotic exposure compared with either a 2% or 20% protein defined nutrient diet. Ex vivo inoculation of cecal contents from antibiotic-treated mice showed decreased toxin production and C. difficile growth in both defined diets compared with a traditional diet. Low protein diets, and defined nutrient diets in general, were found to be protective against CDI in mice. Associated diet-induced alterations in intestinal microbiota may influence colonization resistance and clostridial toxin production in a defined nutrient diet compared to a traditional diet, leading to increased survival. However, mechanisms which led to survival differences between 2% and 20% protein defined nutrient diets need to be further elucidated.