From Antimicrobial Resistance to Regenerative Failure: Reframing Antimicrobial Resistance as a Barrier to Microbiome-driven Tissue Repair

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BSTRACT

Antimicrobial resistance (AMR) is typically framed as an infectious disease crisis; however, emerging evidence suggests broader biological consequences. Antimicrobial pressure and resistant biofilm ecosystems disrupt microbial homeostasis, alter metabolite signaling, sustain inflammation, and impair tissue repair across multiple organ systems. The implications of AMR for regeneration remain underexplored. This narrative review synthesized 11 peer-reviewed studies identified through structured searches of PubMed/MEDLINE, Scopus, and Web of Science Core Collection. Studies examining interactions between antimicrobial exposure, microbiome alterations, and tissue repair in oral, intestinal, cutaneous, metabolic, and pancreatic contexts were included. A qualitative, mechanism-oriented synthesis integrated findings across heterogeneous evidence. Evidence converges on a shared mechanistic axis linking dysbiosis to impaired regeneration. Microbiome-derived metabolites, including short-chain fatty acids and tryptophan derivatives, support epithelial integrity, stem-cell function, and resolution of inflammation. In contrast, antimicrobial-driven dysbiosis promotes persistent biofilms, chronic interleukin-17-mediated inflammation, neutrophil extracellular trap formation, and loss of microbial resilience. Although direct AMR-specific regenerative endpoints are limited, studies in periodontitis, peri-implantitis, chronic wounds, ulcerative colitis, diabetes, and acute pancreatitis consistently show that microbiome-aware or antibiotic-sparing strategies improve the regenerative environment. These include antimicrobial peptides, responsive hydrogels, nanozymes, metabolite restoration, and biofilm-targeted biomaterials. AMR should be reframed as a driver of regenerative dysfunction mediated through microbiome disruption. Antimicrobial stewardship may serve as a regenerative strategy. Future studies should integrate microbiome, metabolomic, immune, and tissue-healing endpoints to support regeneration-preserving anti-infective care.