Hoek Milan J A van, Merks Roeland M H
Life Sciences Group, Centrum Wiskunde & Informatica, Science Park 123, Amsterdam, 1098 XG, The Netherlands.
Mathematical Institute, Leiden University, Niels Bohrweg 1, Leiden, 2333, CA, The Netherlands.
BMC Syst Biol. 2017 May 16;11(1):56. doi: 10.1186/s12918-017-0430-4.
The human gut contains approximately 10 bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution.
In this model, cross-feeding interactions emerge readily, despite the species' ability to metabolize sugars autonomously. Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea.
In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall.
人类肠道中约含有10种细菌，分属于数百个不同的物种。这些微生物物种共同构成了一个复杂的食物网，能够分解我们自身消化酶无法处理的营养源，包括复杂多糖，产生短链脂肪酸和其他代谢产物，如维生素K。微生物多样性对结肠健康很重要：微生物群组成的变化与炎症性肠病、糖尿病、肥胖症和克罗恩病有关，还会使微生物群更容易受到有害物种的侵扰，如艰难梭菌。为了掌握肠道微生物多样性的控制因素，我们在此提出一个多尺度、时空动态通量平衡分析模型，以研究在类似肠道的管状空间环境中代谢多样性的出现。该模型的特点包括微生物种群的基因组尺度代谢模型（GEM）、通过细胞外代谢产物进行资源共享以及空间种群动态和进化。
在这个模型中，尽管物种能够自主代谢糖类，但交叉喂养相互作用很容易出现。有趣的是，群落需要通过交叉喂养才能从葡萄糖输入中产生一组实际的短链脂肪酸。如果我们让微生物亚群的组成在相邻空间的入侵过程中发生变化，就会进化出一个复杂且分层的微生物群，其中亚种通过补偿性性状丧失机制专门进行交叉喂养相互作用。如果增强通过肠道的通量以模拟腹泻，微生物多样性和分层就会崩溃。
总之，这个计算机模拟模型是系统生物学中预测和解释肠道微生物多样性控制因素的有用工具。它可以扩展到包括例如复杂营养源以及通过肠壁的宿主-微生物群相互作用。
