Microbiome diversity protects against pathogens by nutrient blocking

The human gut microbiome plays an important role in resisting colonisation of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonisation of two major bacterial pathogens, both in vitro and in gnotobiotic mice. While single species alone had negligible effects, colonisation resistance greatly increased with community diversity. Moreover, this community-level resistance rested critically upon certain species being present. We explain these ecological patterns via the collective ability of resistant communities to consume nutrients that overlap with those used by the pathogen. Further, we apply our findings to successfully predict communities that resist a novel target strain. Our work provides a reason why microbiome diversity is beneficial and suggests a route for the rational design of pathogen-resistant communities.

人体肠道微生物组（human gut microbiome）在抵御病原体定植宿主的过程中发挥着关键作用，但目前我们仍无法精准预测哪些微生物群落可发挥保护性定植抵抗作用。本研究通过体外实验与限菌小鼠（gnotobiotic mice）模型，探究了人体肠道细菌对两种主要细菌性病原体定植过程的影响。尽管单一肠道细菌菌株的定植抵抗效果可忽略不计，但群落多样性的提升可显著增强定植抵抗能力。此外，这种群落水平的定植抵抗能力关键依赖于特定物种的存在。我们借助抗性群落与病原体共享营养物质的集体代谢能力，阐释了上述生态学规律。进一步地，我们将研究结论应用于实践，成功预测出可抵御新型目标菌株的微生物群落。本研究阐明了微生物组多样性具有益处的内在机制，并为理性设计抗病原体微生物群落提供了可行路径。