Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland.
Institute of Microbiology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Elife. 2023 Feb 9;12:e81212. doi: 10.7554/eLife.81212.
Many microbiota-based therapeutics rely on our ability to introduce a microbe of choice into an already-colonized intestine. In this study, we used genetically barcoded () strains to quantify population bottlenecks experienced by a population during colonization of the mouse gut. As expected, this reveals an inverse relationship between microbiota complexity and the probability that an individual wildtype clone will colonize the gut. The polysaccharide capsule of is important for resistance against attacks from other bacteria, phage, and the host immune system, and correspondingly acapsular loses in competitive colonization against the wildtype strain. Surprisingly, the acapsular strain did not show a colonization defect in mice with a low-complexity microbiota, as we found that acapsular strains have an indistinguishable colonization probability to the wildtype strain on single-strain colonization. This discrepancy could be resolved by tracking in vivo growth dynamics of both strains: acapsular shows a longer lag phase in the gut lumen as well as a slightly slower net growth rate. Therefore, as long as there is no niche competitor for the acapsular strain, this has only a small influence on colonization probability. However, the presence of a strong niche competitor (i.e., wildtype , SPF microbiota) rapidly excludes the acapsular strain during competitive colonization. Correspondingly, the acapsular strain shows a similarly low colonization probability in the context of a co-colonization with the wildtype strain or a complete microbiota. In summary, neutral tagging and detailed analysis of bacterial growth kinetics can therefore quantify the mechanisms of colonization resistance in differently-colonized animals.
许多基于微生物组的疗法依赖于我们将所选微生物引入已定植肠道的能力。在这项研究中，我们使用遗传条形码标记的 () 菌株来量化群体在定植小鼠肠道过程中经历的种群瓶颈。正如预期的那样，这揭示了微生物组复杂性与个体野生型 () 克隆定植肠道的概率之间的反比关系。 的多糖荚膜对于抵抗来自其他细菌、噬菌体和宿主免疫系统的攻击很重要，相应地，无荚膜的 () 在与野生型菌株的竞争定植中会丧失优势。令人惊讶的是，无荚膜菌株在微生物组复杂性低的小鼠中没有表现出定植缺陷，因为我们发现无荚膜菌株在单菌株定植时与野生型菌株具有相同的定植概率。这种差异可以通过跟踪两种菌株的体内生长动态来解决：无荚膜的 () 在肠道腔中表现出更长的迟滞期以及略慢的净生长率。因此，只要无荚膜菌株没有适合的生态位竞争者，这对定植概率的影响很小。然而，当存在强大的生态位竞争者（即野生型、SPF 微生物组）时，无荚膜菌株在竞争定植过程中会迅速被排除。相应地，无荚膜菌株在与野生型菌株或完整微生物组共同定植的情况下，定植概率也相似较低。总之，因此，中性标记和对细菌生长动力学的详细分析可以定量评估在不同定植动物中定植抗性的机制。
