Heinken Almut, Thiele Ines
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg.
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg Faculty of Science, Technology and Communication, University of Luxembourg, Belval, Luxembourg
Appl Environ Microbiol. 2015 Jun 15;81(12):4049-61. doi: 10.1128/AEM.00101-15. Epub 2015 Apr 3.
The human gut is inhabited by thousands of microbial species, most of which are still uncharacterized. Gut microbes have adapted to each other's presence as well as to the host and engage in complex cross feeding. Constraint-based modeling has been successfully applied to predicting microbe-microbe interactions, such as commensalism, mutualism, and competition. Here, we apply a constraint-based approach to model pairwise interactions between 11 representative gut microbes. Microbe-microbe interactions were computationally modeled in conjunction with human small intestinal enterocytes, and the microbe pairs were subjected to three diets with various levels of carbohydrate, fat, and protein in normoxic or anoxic environments. Each microbe engaged in species-specific commensal, parasitic, mutualistic, or competitive interactions. For instance, Streptococcus thermophilus efficiently outcompeted microbes with which it was paired, in agreement with the domination of streptococci in the small intestinal microbiota. Under anoxic conditions, the probiotic organism Lactobacillus plantarum displayed mutualistic behavior toward six other species, which, surprisingly, were almost entirely abolished under normoxic conditions. This finding suggests that the anoxic conditions in the large intestine drive mutualistic cross feeding, leading to the evolvement of an ecosystem more complex than that of the small intestinal microbiota. Moreover, we predict that the presence of the small intestinal enterocyte induces competition over host-derived nutrients. The presented framework can readily be expanded to a larger gut microbial community. This modeling approach will be of great value for subsequent studies aiming to predict conditions favoring desirable microbes or suppressing pathogens.
人类肠道中栖息着数千种微生物，其中大多数仍未得到充分描述。肠道微生物已适应彼此的存在以及宿主，并进行复杂的交叉喂养。基于约束的建模已成功应用于预测微生物与微生物之间的相互作用，如共生、互利共生和竞争。在这里，我们应用基于约束的方法对11种代表性肠道微生物之间的成对相互作用进行建模。微生物与微生物之间的相互作用与人类小肠肠上皮细胞一起进行计算建模，并且在常氧或缺氧环境中，将微生物对置于含有不同水平碳水化合物、脂肪和蛋白质的三种饮食中。每种微生物都参与了物种特异性的共生、寄生、互利共生或竞争相互作用。例如，嗜热链球菌有效地胜过了与其配对的微生物，这与链球菌在小肠微生物群中的主导地位一致。在缺氧条件下，益生菌植物乳杆菌对其他六种物种表现出互利共生行为，令人惊讶的是，在常氧条件下这种行为几乎完全消失。这一发现表明，大肠中的缺氧条件驱动了互利共生的交叉喂养，导致了一个比小肠微生物群更复杂的生态系统的进化。此外，我们预测小肠肠上皮细胞的存在会引发对宿主衍生营养物质的竞争。所提出的框架可以很容易地扩展到更大的肠道微生物群落。这种建模方法对于后续旨在预测有利于理想微生物或抑制病原体的条件的研究将具有巨大价值。
