Negative interactions determine Clostridioides difficile growth in synthetic human gut communities.
Negative interactions determine Clostridioides difficile growth in synthetic human gut communities.
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DOI：
10.15252/msb.202110355
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发表时间：
2021-10
影响因子：
9.9
通讯作者：
Venturelli OS
中科院分区：
文献类型：
--
作者：
Hromada S;Qian Y;Jacobson TB;Clark RL;Watson L;Safdar N;Amador-Noguez D;Venturelli OS
了解肠道微生物组对病原体艰难梭菌的定殖抗性的原理将能够设计确定的细菌治疗剂。我们使用合成的人类肠道微生物组研究了社区对艰难梭菌的抗性的生态学原理。使用动态计算模型，我们证明了艰难梭菌接收最大数量和幅度的传入负面相互作用。我们的研究结果表明，艰难梭菌是一类独特的物种，表现出强烈的负相关性之间的增长和物种丰富度。我们确定了抑制的分子机制，包括环境酸化和资源竞争。我们证明，Clostridium hiranonis强烈抑制艰难梭菌部分通过资源竞争。增加艰难梭菌的初始密度可以增加其在组装的群落中的丰度，但群落环境决定了最大可实现的艰难梭菌丰度。我们的工作表明，可以通过设计具有包括物种丰富度，环境酸化和资源竞争在内的机制组合的社区来优化确定的细菌治疗剂的艰难梭菌抑制潜力。自下而上的社区组装和计算建模的结合揭示了合成人类肠道社区中艰难梭菌生长的决定因素。
Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition. A combination of bottom‐up community assembly and computational modeling reveals determinants of Clostridioides difficile growth in synthetic human gut communities.