IBD is associated with species-specific changes in gut microbial gene diversity

ABSTRACT Intra-species genomic variation provides the raw material for natural selection and can reflect the recent diversification history of microbial populations. Environmental stress may be regarded as the ultimate accelerator of the evolutionary process, especially for microorganisms, which can alter their DNA if presented with nutrient limitation, toxins, or pathogen attack. Chronic intestinal inflammation, as in inflammatory bowel disease (IBD), represents prolonged environmental stress for gut commensal bacteria, bringing many enteric species down to undetectable levels. However, it remains unclear how microbes that colonize IBD patients actually respond to IBD-associated stressors and whether stress-driven bacterial dynamics may be identified at the population level from the bacterial gut metagenome. To investigate IBD-associated strain-level population dynamics, we performed metagenomic analyses focusing on measuring within-individual bacterial diversity for a panel of gut commensals present across IBD patients and Controls. First, we found species-specific differences in genome-level bacterial diversity. Then, we found that certain genes and functions may harbor different levels and kinds of genetic divergence within the same species across IBD patients and Controls. Functions that were enriched in IBD with both neutral divergence and functional divergence were associated with motility and iron-scavenging, among others. These results may point toward functions that are under selection in the context of IBD stress and could inform future mechanistic work, exploring previously unknown routes of bacterial diversification and adaptation to stress in the gut microbiome. IMPORTANCE Inflammatory bowel disease (IBD) is characterized by profound alterations in the gut microbiome composition, and most research so far has focused on changes in species-level abundance to understand gut microbiome contributions to disease dynamics. However, investigating strain-level variation has the potential to uncover previously unknown factors underlying bacterial persistence during gut inflammation, hence revealing key aspects driving gut dysbiosis. Here, we showed that IBD is associated with species-specific changes in gut microbial population-level genetic diversity and identified individual genes and functions that seem to harbor differential genetic diversity within IBD-associated strains. More broadly, our results highlight how intra-species population- and gene-level diversity could be used as sensors of environmental stress in the gut microbiome, and further studies could follow up on the functions highlighted in this work to establish causal links between gut inflammatory conditions and processes of bacterial adaptation to stress.