Department of Chemical Engineering, University of Massachusetts, Amherst, Massachusetts, USA.
Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts, USA.
PLoS Comput Biol. 2018 Oct 30;14(10):e1006558. doi: 10.1371/journal.pcbi.1006558. eCollection 2018 Oct.
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.
肠道微生物群代表了一个高度复杂的生态系统,大约由 1000 种物种组成,与人类宿主形成共生关系。微生物群的一个关键属性是高度的物种多样性,它通过重叠和冗余的代谢能力提供系统的鲁棒性。细菌多样性的逐渐丧失与广泛的肠道病理学和疾病有关,包括营养不良、肥胖、糖尿病和炎症性肠病。我们通过组合 28 个代表性物种的基因组规模代谢重建来构建肠道微生物群的计算群落模型,以探索物种多样性和群落生长之间的关系。虽然单个物种提供了广泛的代谢能力,但优化为最大化生长的社区在模拟的西方饮食和高纤维饮食中具有低多样性和短链脂肪酸 (SCFA) 合成的不平衡,其特征是乙酸盐过量产生。使用 28 个物种模型和简化的 20 个物种模型进行的群落通量可变性分析表明,在次优生长速率下可以实现增强的物种多样性和更平衡的 SCFA 产生。我们开发了一种简单的方法来约束物种丰度,以采样生长多样性的权衡,并使用 20 个物种模型表明,西方饮食和高纤维饮食的权衡曲线类似于帕累托最优曲面。与最大生长解决方案相比,次优生长解决方案的特点是物种多样性更高,SCFA 合成更平衡,更多物种之间的交叉喂养代谢物交换率更低。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,并建议需要允许生长和多样性的多目标优化的群落代谢建模方法来更真实地模拟复杂群落。