A metagenomics pipeline reveals insertion sequence-driven evolution of the microbiota

Insertion sequence (IS) elements are mobile genetic elements in bacterial genomes that support adaptation. We developed a database of IS elements coupled to a computational pipeline that identifies IS element insertions in the microbiota. We discovered that diverse IS elements insert into the genomes of intestinal bacteria regardless of human host lifestyle. These insertions target bacterial accessory genes that aid in their adaptation to unique environmental conditions. Using IS expansion in Bacteroides, we show that IS activity leads to the insertion of “hot spots” in accessory genes. We show that IS insertions are stable and can be transferred between humans. Extreme environmental perturbations force IS elements to fall out of the microbiota, and many fail to rebound following homeostasis. Our work shows that IS elements drive bacterial genome diversification within the microbiota and establishes a framework for understanding how strain-level variation within the microbiota impacts human health. [Display omitted] •Insertion sequence (IS) element database and pipeline identify IS insertions•Intestinal bacteria have diverse IS insertions maintained over long timescales•IS insertions are enriched in accessory genes, such as susCD/tonB transporters•IS insertion activity is sensitive to perturbation (e.g., nutrients and phage) Insertion sequence (IS) elements are small transposons found in the genomes of bacteria. Leveraging an assembled database of IS elements, Kirsch et al. developed a computational pipeline that reveals the presence, abundance, and dynamics of IS insertions in the human intestinal microbiota with high resolution.