{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:28:50Z","timestamp":1782970130984,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chronic wounds represent a substantial and growing clinical burden, yet durable healing remains difficult to achieve in a large proportion of patients. The skin microbiome plays a central role in this challenge: in healthy tissue, resident microorganisms support barrier integrity and calibrate immune responses, whereas in chronic wounds, community disruption\u2014often combined with persistent biofilm formation\u2014drives non-resolving inflammation, impairs re-epithelialisation, and increases antimicrobial tolerance. As antibiotic resistance escalates, these features strengthen the rationale for microbiome-directed strategies that target wound ecology while reducing reliance on conventional antimicrobials. Current evidence is still dominated by mechanistic and preclinical studies, with only early clinical signals for selected approaches; therefore, next-generation probiotics, including Lactiplantibacillus\/Lactobacillus spp., as well as defined prebiotic and postbiotic formulations, should be interpreted as promising adjuncts rather than clinically established therapies. Causal mechanisms, optimal formulations, reproducibility, and patient-level determinants of response remain insufficiently defined, representing a critical knowledge gap that limits translation. Here, we synthesise current evidence linking microbial ecology to key wound-healing pathways and propose a precision framework that integrates metagenomics, transcriptomics, metabolomics, and spatial profiling to map host\u2013microbe interactions, identify predictive biomarkers, and guide stratified therapy. We further highlight combinatorial approaches pairing ecological engineering with biofilm-disruptive materials and immune-modulatory molecules. Realising the potential of these interventions will require mechanism-resolved clinical trials, standardised outcome frameworks, and patient stratification tools\u2014advances that could improve chronic wound management while reducing selective pressure for antimicrobial resistance.<\/jats:p>","DOI":"10.3390\/molecules31132229","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:03:56Z","timestamp":1782349436000},"page":"2229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiome-Driven Bioactives for Chronic Wound Repair: Microbial Metabolites, Host\u2013Microbe Mechanisms and Paths to Clinical Translation"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-3874","authenticated-orcid":false,"given":"Juliana","family":"Garcia","sequence":"first","affiliation":[{"name":"AquaValor, Centro de Valoriza\u00e7\u00e3o e Transfer\u00eancia de Tecnologia da \u00c1gua, Associa\u00e7\u00e3o, Rua Dr. J\u00falio Martins n\u00ba 1, 5400-342 Chaves, Portugal"},{"name":"LiveWell, Research Centre for Active Living & Wellbeing, Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"},{"name":"Centre for the Research and Technology of Agroenvironmental and Biological Sciences, CITAB, Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production, Inov4Agro, Universidade de Tr\u00e1s-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5868-4669","authenticated-orcid":false,"given":"Jani","family":"Silva","sequence":"additional","affiliation":[{"name":"AquaValor, Centro de Valoriza\u00e7\u00e3o e Transfer\u00eancia de Tecnologia da \u00c1gua, Associa\u00e7\u00e3o, Rua Dr. J\u00falio Martins n\u00ba 1, 5400-342 Chaves, Portugal"},{"name":"LiveWell, Research Centre for Active Living & Wellbeing, Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-4393","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Alves","sequence":"additional","affiliation":[{"name":"AquaValor, Centro de Valoriza\u00e7\u00e3o e Transfer\u00eancia de Tecnologia da \u00c1gua, Associa\u00e7\u00e3o, Rua Dr. J\u00falio Martins n\u00ba 1, 5400-342 Chaves, Portugal"},{"name":"LiveWell, Research Centre for Active Living & Wellbeing, Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"},{"name":"CIMO, Centro de Investiga\u00e7\u00e3o de Montanha, Instituto Polit\u00e9cnico de Bragan\u00e7a, 5300-253 Bragan\u00e7a, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-4958","authenticated-orcid":false,"given":"Irene","family":"Gouvinhas","sequence":"additional","affiliation":[{"name":"Animal and Veterinary Research Center (CECAV), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Associate Laboratory of Animal and Veterinary Sciences (AL4AnimalS), 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/wrr.12683","article-title":"The humanistic and economic burden of chronic wounds: A systematic review","volume":"27","author":"Olsson","year":"2019","journal-title":"Wound Repair Regen."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/bjd.13954","article-title":"Cellular and molecular mechanisms of repair in acute and chronic wound healing","volume":"173","author":"Martin","year":"2015","journal-title":"Br. 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