Despite pervasive bacterial colonization of cutaneous wounds, the wound microbiome has yet to be harnessed for wound therapies. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to healing. In chapter 2 we focus on Alcaligenes faecalis, a bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes re-epithelialization of diabetic keratinocytes, a process which is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. In chapter 3, we focus on the wound pathogen S. aureus and identify a mechanism of bacterial-driven delays in wound healing. We performed phenotyping screens on S. aureus isolates from diabetic foot ulcers and discovered that isolates from non-healing wounds produced more staphyloxanthin, a cell membrane pigment. In a murine diabetic wound model, staphyloxanthin-producing isolates delayed wound closure significantly compared to staphyloxanthin-deficient isolates. Staphyloxanthin promoted resistance to oxidative stress and enhanced bacterial survival in neutrophils. Clinical isolates with disparate staphyloxanthin phenotypes have a mutation in the Sigma B operon that resulted in marked differences in stress response gene expression. In chapter 4, we focus on canine perianal fistulas, which are painful ulcers or sinus tracts that have been proposed as a spontaneous animal model of fistulizing Crohn’s disease. In this study, we characterized the rectal microbiota and cutaneous microbiota, both lesional and non-lesional, in dogs with perianal fistulas and investigated the longitudinal shifts associated with lesion resolution during immunodulatory therapy. We find that changes in lesional cutaneous and rectal microbiota occur in dogs with perianal fistulas and shift over time with during immunomodulatory therapy. Together, this work uncovers two mechanisms of bacterial-driven healing outcomes and provides a foundation for the development of microbiota-based wound interventions.