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

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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.