Distinct Evolutionary Selection Patterns in Temperate and Filamentous Phages of Phocaeicola vulgatus in Health and...

The gut virome is profoundly altered in inflammatory bowel disease (IBD), though phage evolution during inflammation remains poorly understood. We used viral tagging (VT) to recover phages of Phocaeicola vulgatus , a gut-associated pathobiont, from healthy and Crohn's disease (CD) viromes, revealing phages related to the tailed phage BV01, and the first filamentous phage (PvIno1) of any Bacteroidaceae host. BV01-like phages accumulated point mutations in tail genes during health, diversity which was lost in CD, while the configuration of a tail-fiber shufflon varied with disease state. In PvIno1, diversification was concentrated to a regulatory region, rather than structural genes as in BV01-like phages. Together, these findings indicate that inflammation imposes unique evolutionary pressures on distinct phages types. Integrating evolutionary dynamics with current ecological models of the IBD phageome is a critical step toward designing phage-based therapeutics for gut dysbiosis and understanding the complex interactions between phages, bacteria, and human hosts.