Long-term evolution and short-term adaptation of microbiota strains and sub-strains

Long-term evolution and short-term adaptation of microbiota strains and sub-strainsCatherine Mooser1,2,9, Bahtiyar Yilmaz1,2,9, Irene Keller1,3,9, Lars Bosshard3,8, Jakob Zimmermann1,2, Tobias Fuhrer4, Mercedes Gomez de Agüero1,2, Heidi Tschanz-Lischer1,3, Hai Li1,2, Julien P. Limenitakis1,2, Wolf-Dietrich Hardt5, Kathy D. McCoy1,2, Bärbel Stecher6,7, Laurent Excoffier3,8, Uwe Sauer4, Stephanie C. Ganal-Vonarburg1,2, Andrew J. Macpherson1,2,*SUMMARYStable animal models are essential to reproducibly investigate mechanisms of host-microbial mutualism. Isobiotic mice, with an identical stable microbiota composition, potentially allow models of host-microbial mutualism to be studied over time and between different laboratories. To understand how microbiota evolution occurs in these models, we carried out a 6-year experiment in mice colonized with 12 representative fully-sequenced taxa. External introduction of new taxa was strictly avoided to distinguish microbiota evolution without confounding immigrant microbes. Increased non-synonymous to synonymous mutation fixation rates (dN/dS > 1) indicated positive selection in multiple taxa, particularly for genes annotated for nutrient acquisition or replication. Microbial sub-strains that had evolved within a single taxon were able to stably coexist, consistent with niche partitioning of ecotypes in the complex intestinal environment. Dietary shifts triggered rapid transcriptional adaptation to macronutrient and micronutrient changes in individual taxa and alterations in taxa biomass. The proportions of different sub-strains were also rapidly altered after dietary shift. This indicates that microbial taxa adapt to changes in the intestinal environment by long-term genomic positive selection and short-term effects of transcriptional reprogramming and adjustments in sub-strain proportions.