Bacterial evolution during chronic inflammation and its potential for ancestral state restorative therapy

自然选择适应的基本进化原理适用于我们肠道中的细菌。即使在人的一生中，细菌也会作为健康个体微生物群的成员而进化。进化理论预测，炎症性肠病（IBD）期间的肠道环境为细菌特征的进化创造了额外的选择压力，我们目前还没有意识到这一点，我们可能会利用这一点来帮助恢复患者的微生物群。为了验证这一假设，我们将在IBD小鼠模型中进行进化实验，以识别和表征疾病背景下选择下的细菌特征。我们的目标是：(i)确定在慢性炎症期间选择的细菌特征；（ii）确定在存在和不存在炎症的情况下进化特征的相对成本和收益；（iii）测试细菌祖先在缓解期间战胜进化变异的能力，以治疗性地恢复微生物群；（iv）追踪患者的细菌进化，以测试祖先状态恢复疗法的潜力；发展和应用创新的成像方法，以确定细菌进化出的适应性表型的性质。我们的研究结果将提高我们对IBD期间微生物群变化的理解，并为基于进化医学的治疗应用提供原理证明。

The basic evolutionary principle of adaptation by natural selection applies to bacteria in our intestine. Even within a person’s lifetime, bacteria evolve as members of the microbiota in healthy individuals. Evolutionary theory predicts that the intestinal environment during inflammatory bowel diseases (IBD) creates additional selection pressures for the evolution of bacterial traits we are currently not aware of, and that we might take advantage of to help restore a patient’s microbiota. To test this hypothesis, we will perform evolution experiments in a mouse model of IBD to identify and characterize bacterial traits under selection in the context of disease. Our aims are to (i) Identify bacterial traits that are selected for during chronic inflammation; (ii) Determine the relative costs and benefits of evolved traits in the presence and absence of inflammation; (iii) Test the ability of the bacterial ancestor to outcompete evolved variants during remission to therapeutically restore the microbiota; (iv) Track bacterial evolution in patients to test the potential for ancestral state restorative therapy; (v) Develop and apply innovative imaging methods to characterize the nature of adaptive phenotypes evolved by bacteria. Our results will improve our understanding of the altered microbiota during IBD and provide the proof of principle for a therapeutic application based on evolutionary medicine.