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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut
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Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut

机译:史密斯甲烷短杆菌对人类肠道的基因组和代谢适应

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The human gut is home to trillions of microbes, thousands of bacterial phylotypes, as well as hydrogen-consuming methanogenic archaea. Studies in gnotobiotic mice indicate that Methanobrevibacter smithii, the dominant archaeon in the human gut ecosystem, affects the specificity and efficiency of bacterial digestion of dietary polysaccharides, thereby influencing host calorie harvest and adiposity. Metagenomic studies of the gut microbial communities of genetically obese mice and their lean littermates have shown that the former contain an enhanced representation of genes involved in polysaccharide degradation, possess more archaea, and exhibit a greater capacity to promote adiposity when transplanted into germ-free recipients. These findings have led to the hypothesis that M. smithii may be a therapeutic target for reducing energy harvest in obese humans. To explore this possibility, we have sequenced its 1,853, 160-bp genome and compared it to other human gut-associated M. smithii strains and other Archaea. We have also examined M. smithii's transcriptome and metabolome in gnotobiotic mice that do or do not harbor Bacte-roides thetaiotaomicron, a prominent saccharolytic bacterial member of our gut microbiota. Our results indicate that M. smithii is well equipped to persist in the distal intestine through (ⅰ) production of surface glycans resembling those found in the gut mucosa, (ⅱ) regulated expression of adhesin-like proteins, (ⅲ) consumption of a variety of fermentation products produced by saccharolytic bacteria, and (ⅳ) effective competition for nitrogenous nutrient pools. These findings provide a framework for designing strategies to change the representation and/or properties of M. smithii in the human gut microbiota.
机译:人类的肠道拥有数万亿个微生物,数千种细菌菌型以及耗氢的产甲烷古细菌。 gnotobiotic小鼠的研究表明,人类肠道生态系统中占主导地位的古细菌Methanobrevibacter smithii影响膳食多糖的细菌消化的特异性和效率,从而影响宿主的热量收集和肥胖。对遗传性肥胖小鼠及其瘦肉同窝仔的肠道微生物群落的元基因组学研究表明,前者包含与多糖降解有关的基因的增强表示,拥有更多的古细菌,并且在移植到无菌受体中时具有更大的促进肥胖的能力。 。这些发现导致了假说史密斯氏菌可能是减少肥胖人类能量收集的治疗靶点的假设。为了探索这种可能性,我们已经对其1,853个160 bp的基因组进行了测序,并将其与其他与人类肠道相关的史密斯氏菌和其他古细菌进行了比较。我们还检查了在有或没有隐匿细菌-拟杆菌thetaiotaomicron(我们肠道菌群中重要的糖酵解细菌成员)的生生物小鼠中的M. smithii的转录组和代谢组。我们的结果表明,史密斯分枝杆菌通过(ⅰ)产生类似于在肠粘膜中发现的表面聚糖,(ⅱ)调节粘附素样蛋白的表达,(ⅲ)食用各种糖,可以在远端肠中持久生存。糖酵解细菌产生的发酵产物,以及(ⅳ)有效竞争含氮营养库。这些发现为设计策略以改变人类肠道菌群中史密斯氏菌的表达和/或特性提供了框架。

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