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

慢性炎症期间的细菌进化及其用于祖先状态恢复治疗的潜力

• 批准号: 436131115
• 负责人: Professor Dr. John F. Baines
• 金额: --
• 依托单位: Institut für Experimentelle Medizin (IEM)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/436131115?language=en
• 关键词: Bacterial; evolution; during; chronic; inflammation

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.

自然选择适应的基本进化原理适用于我们肠道中的细菌。即使在一个人的一生中，细菌也会作为健康个体的微生物群成员进化。进化理论预测，炎症性肠病（IBD）期间的肠道环境为我们目前不知道的细菌特征的进化创造了额外的选择压力，我们可能会利用这些压力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，以鉴定和表征疾病背景下选择的细菌性状。我们的目标是（i）鉴定在慢性炎症期间选择的细菌性状;（ii）确定在存在和不存在炎症的情况下进化性状的相对成本和益处;（iii）测试细菌祖先在缓解期间胜过进化变体以治疗性恢复微生物群的能力; ㈣追踪病人体内的细菌演变，以测试祖先状态恢复疗法的潜力; ㈤开发和应用创新的成像方法，以确定细菌演变的适应性表型的性质。我们的研究结果将提高我们对IBD期间改变的微生物群的理解，并为基于进化医学的治疗应用提供原理证明。