Inflammatory Bowel Disease (IBD) is marked by chronic epithelial injury and impaired healing in response to inflammatory and microbial stimuli. Current treatments target chronic inflammation, while regenerative interventions remain an unmet clinical need. Intestinal wound healing progresses through distinct phases: peak injury, repair, and a return to homeostasis. The repair phase is characterized by specific cellular states, including the upregulation of damage response genes. While prior research on microbe-host interactions during wound healing has focused on the restoration of homeostatic markers, studying damage response markers offers a novel perspective on the microbiota’s role during intestinal regeneration. We aim to elucidate the microbiota’s role during regeneration using a mouse Dextran Sulfate Sodium (DSS) colitis model and hypothesize that gut microbiota promotes colonic wound healing post-DSS injury. Mice were administered DSS and then treated with antibiotics to deplete the microbiota. Histologic and immunofluorescence (IF) stains were used to assess tissue and cellular states at days 7, 14, and 30 post-antibiotic or water administration. In situ hybridization was used to measure damage response and homeostatic gene expression. HALO-AI was used to quantify whole-tissue markers. Mice treated with antibiotics showed significantly reduced epithelial proliferation and tuft cell abundance, with decreased expression of damage response markers during the repair phase. Antibiotic-treated mice also had reduced crypt heights and abnormal crypt morphology compared to controls. Lastly, an in vitro screen using microbial metabolites determined that damage response genes were upregulated in response to certain short-chain fatty acids, suggesting that the microbiota can directly induce a regenerative state in both mouse and human epithelial cells. Altogether, our findings show that the microbiota is crucial to inducing active regenerative mechanisms, regulating epithelial proliferation, crypt morphology and size, and damage response genes over time.