Suboptimal community growth mediated through metabolite crossfeeding promotes species diversity in the gut microbiota.
Suboptimal community growth mediated through metabolite crossfeeding promotes species diversity in the gut microbiota.
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DOI：
10.1371/journal.pcbi.1006558
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发表时间：
2018-10
影响因子：
4.3
通讯作者：
Phalak P
中科院分区：
文献类型：
--
作者：
Henson MA;Phalak P
肠道微生物群代表了一个高度复杂的生态系统，由大约1000个物种组成，与人类宿主形成互惠关系。微生物群的一个关键属性是高度的物种多样性，这通过重叠和冗余的代谢能力提供了系统的鲁棒性。细菌多样性的逐渐丧失与广泛的肠道病理和疾病有关，包括营养不良、肥胖、糖尿病和炎症性肠病。我们通过结合28种代表性物种的基因组规模的代谢重建，制定了肠道微生物群的电子社区模型，以探索物种多样性和社区增长之间的关系。虽然个别物种提供了广泛的代谢能力，社区优化的最大增长模拟西方和高纤维饮食有低的dilution和不平衡的短链脂肪酸（SCFA）的合成特征为醋酸盐生产过剩。与28种模型和减少20种模型进行的社区通量变异分析表明，增强物种多样性和更平衡的SCFA生产是可以实现的次优增长率。我们开发了一种简单的方法来限制物种丰度的增长多样性的权衡，并使用20种模型来显示，西方和高纤维饮食的权衡曲线类似于帕累托最优表面。与最大生长解相比，次优生长解的特征在于更高的物种多样性、更平衡的SCFA合成和更低的物种间交叉代谢物交换率。我们假设，通过宿主-微生物群相互作用调节交叉喂养关系可能是维持物种多样性的重要手段，并建议需要更真实地模拟复杂群落的多目标优化生长和多样性的群落代谢建模方法。肠道微生物群在维持人类宿主的健康状态方面起着关键作用。肠道含有大约1,000种细菌，提供广泛的代谢能力，包括分解膳食化合物和合成有用的代谢物。肠道群落的强大功能与其多样性密切相关，无论是在物种数量还是这些物种的相对丰度方面。多样性的逐渐丧失是微生物群生态失调的关键因素，这与包括炎症性肠病在内的广泛健康问题有关。为了研究肠道微生物群中的物种多样性，我们通过结合人类肠道中最丰富的属的28种代表性物种的基因组规模代谢重建，开发了一个计算机社区模型。我们的模型预测，最大的社区增长产生的物种多样性低，没有促进健康的代谢产物丁酸的合成。在将社区模型减少到20个物种后，我们发现，次优的社区增长允许更高的物种多样性和丁酸合成更符合体内研究。该模型预测，增加的多样性可以通过调节物种之间的代谢物互食关系来实现，这是一个实验可验证的假设。
The gut microbiota represent a highly complex ecosystem comprised of approximately 1000 species that forms a mutualistic relationship with the human host. A critical attribute of the microbiota is high species diversity, which provides system robustness through overlapping and redundant metabolic capabilities. The gradual loss of bacterial diversity has been associated with a broad array of gut pathologies and diseases including malnutrition, obesity, diabetes and inflammatory bowel disease. We formulated an in silico community model of the gut microbiota by combining genome-scale metabolic reconstructions of 28 representative species to explore the relationship between species diversity and community growth. While the individual species offered a broad range of metabolic capabilities, communities optimized for maximal growth on simulated Western and high-fiber diets had low diversities and imbalances in short-chain fatty acid (SCFA) synthesis characterized by acetate overproduction. Community flux variability analysis performed with the 28-species model and a reduced 20-species model suggested that enhanced species diversity and more balanced SCFA production were achievable at suboptimal growth rates. We developed a simple method for constraining species abundances to sample the growth-diversity tradeoff and used the 20-species model to show that tradeoff curves for Western and high-fiber diets resembled Pareto-optimal surfaces. Compared to maximal growth solutions, suboptimal growth solutions were characterized by higher species diversity, more balanced SCFA synthesis and lower exchange rates of crossfed metabolites between more species. We hypothesized that modulation of crossfeeding relationships through host-microbiota interactions could be an important means for maintaining species diversity and suggest that community metabolic modeling approaches that allow multiobjective optimization of growth and diversity are needed for more realistic simulation of complex communities. The gut microbiota serve a critical role in maintaining a healthy state in the human host. The gut contains approximately 1,000 bacterial species that provide a wide range of metabolic capabilities including the breakdown of dietary compounds and the synthesis of useful metabolites. The robust function of the gut community is intimately connected to its diversity, both with respect to the number of species and the relative abundance of those species. The gradual loss of diversity is a key element of microbiota dysbiosis, which has been correlated with a wide range of health problems including inflammatory bowel disease. To investigate species diversity in the gut microbiota, we developed an in silico community model by combining genome-scale metabolic reconstructions of 28 representative species from the most abundant genera in the human gut. Our model predicted that maximal community growth produced low species diversity and no synthesis of the health-promoting metabolite butyrate. After reducing the community model to 20 species, we showed that suboptimal community growth allowed much higher species diversity and butyrate synthesis more consistent with in vivo studies. The model predicted that increased diversity could be achieved through modulation of metabolite crossfeeding relationships between species, an experimentally testable hypothesis.
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DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
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影响因子：
4.4
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DOI：
10.1038/ijo.2015.84
发表时间：
2015-09
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Byrne CS;Chambers ES;Morrison DJ;Frost G
通讯作者：
Frost G
影响因子：
5.2
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