Protein- and zinc-deficient diets modulate the murine microbiome and metabolic phenotype.

Protein- and zinc-deficient diets modulate the murine microbiome and metabolic phenotype.
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DOI:
10.3945/ajcn.116.131797
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发表时间:
2016-11
期刊:
The American journal of clinical nutrition
影响因子:
--
通讯作者:
Guerrant RL
Guerrant RL
中科院分区:
其他
文献类型:
--
作者:
Mayneris-Perxachs J;Bolick DT;Leng J;Medlock GL;Kolling GL;Papin JA;Swann JR;Guerrant RL

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背景资料:环境性肠病与营养不良和慢性感染有关,影响全世界发展中地区儿童的身心发育。了解这些因素如何结合联合收割机来塑造发育结果的关键是首先了解营养缺乏对哺乳动物系统的影响,包括对肠道微生物群的影响。目的:我们通过分析与营养良好的对照组相比,锌或蛋白质缺乏的断奶小鼠模型中发生的特定代谢和肠道微生物群变化,剖析了环境性肠病的营养成分。设计图:通过使用基于1H核磁共振光谱的代谢分析方法和匹配的16 S微生物群分析,在小鼠模型中独立探索蛋白质和锌缺乏对粪便微生物群的代谢后果和特定影响。结果如下:我们发现,在维持正常饮食的小鼠中,断奶后14-24天肠道微生物群发生了相当大的变化(包括变形菌门的增加和拟杆菌门的显著减少)。虽然缺锌的微生物群与年龄匹配的营养良好的概况相当,但蛋白质限制的微生物群在组成上仍然更接近于保留拟杆菌的断奶肠型。断奶后14天,在营养良好和蛋白质缺乏的小鼠中均观察到疣微菌(主要是嗜粘蛋白阿克曼氏菌)显著增加。我们发现,蛋白质营养不良会损害生长,并产生主要的代谢后果(比缺锌严重得多),包括能量、多胺、嘌呤和嘧啶代谢的改变。与肠道微生物群的主要变化一致,观察到微生物蛋白水解的减少和微生物膳食胆碱加工的增加。结论:这些发现与我们以前在营养不良儿童中观察到的代谢改变一致。结果表明,我们可以模拟小鼠营养不良的代谢后果,以帮助剖析营养不良影响及其对环境肠道功能障碍的贡献的相关途径。
Background: Environmental enteropathy, which is linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide. Key to understanding how these factors combine to shape developmental outcomes is to first understand the effects of nutritional deficiencies on the mammalian system including the effect on the gut microbiota. Objective: We dissected the nutritional components of environmental enteropathy by analyzing the specific metabolic and gut-microbiota changes that occur in weaned-mouse models of zinc or protein deficiency compared with well-nourished controls. Design: With the use of a 1H nuclear magnetic resonance spectroscopy–based metabolic profiling approach with matching 16S microbiota analyses, the metabolic consequences and specific effects on the fecal microbiota of protein and zinc deficiency were probed independently in a murine model. Results: We showed considerable shifts within the intestinal microbiota 14–24 d postweaning in mice that were maintained on a normal diet (including increases in Proteobacteria and striking decreases in Bacterioidetes). Although the zinc-deficient microbiota were comparable to the age-matched, well-nourished profile, the protein-restricted microbiota remained closer in composition to the weaned enterotype with retention of Bacteroidetes. Striking increases in Verrucomicrobia (predominantly Akkermansia muciniphila) were observed in both well-nourished and protein-deficient mice 14 d postweaning. We showed that protein malnutrition impaired growth and had major metabolic consequences (much more than with zinc deficiency) that included altered energy, polyamine, and purine and pyrimidine metabolism. Consistent with major changes in the gut microbiota, reductions in microbial proteolysis and increases in microbial dietary choline processing were observed. Conclusions: These findings are consistent with metabolic alterations that we previously observed in malnourished children. The results show that we can model the metabolic consequences of malnutrition in the mouse to help dissect relevant pathways involved in the effects of undernutrition and their contribution to environmental enteric dysfunction.
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