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This review provides an integrated overview of the bidirectional relationship between MGO-derived carbonyl stress and the gut microbiota, focusing on its implications for ageing and age-related diseases. We summarize current evidence on MGO production, clearance, tissue distribution, and reactivity, with particular attention to the intestinal lumen as a site where dietary compounds, host metabolism, and microbial activity converge. Age-related dysbiosis may impair intestinal barrier integrity, alter microbial metabolite production, and promote chronic low-grade inflammation, thereby reinforcing metabolic dysfunction and favoring free MGO accumulation. Conversely, MGO and AGEs can reshape microbial communities, compromise epithelial tight junctions, and amplify inflammatory signalling through receptor-dependent and independent mechanisms. Evidence from in vitro, animal, and clinical studies supports a role for the MGO\u2013microbiota axis in metabolic, cardiovascular, gastrointestinal, neurodegenerative, and frailty-related conditions. Targeting microbiota composition, intestinal barrier function, and MGO scavenging pathways may therefore represent a promising strategy to mitigate carbonyl stress and preserve health during ageing.<\/jats:p>","DOI":"10.3390\/life16081265","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:20:18Z","timestamp":1785486018000},"page":"1265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microbiota and Methylglyoxal-Derived AGEs: Implications in Ageing and Age-Related Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6007-5862","authenticated-orcid":false,"given":"Niki","family":"Tombolesi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Marche University Hospital, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Francini","sequence":"additional","affiliation":[{"name":"Clinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-663X","authenticated-orcid":false,"given":"Gretta Veronica","family":"Badillo-Pazmay","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9591-7920","authenticated-orcid":false,"given":"Carlo","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4899-6073","authenticated-orcid":false,"given":"Francesca","family":"Marchegiani","sequence":"additional","affiliation":[{"name":"Clinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9606-1144","authenticated-orcid":false,"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA, 60121 Ancona, Italy"},{"name":"Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Universit\u00e0 Politecnica delle Marche, 60100 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5524-741X","authenticated-orcid":false,"given":"Stefania","family":"Fumarola","sequence":"additional","affiliation":[{"name":"Center of Biogerontology, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Maniscalco","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-3903","authenticated-orcid":false,"given":"Giulia","family":"Matacchione","sequence":"additional","affiliation":[{"name":"Clinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12987-023-00477-6","article-title":"Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity","volume":"20","author":"Berends","year":"2023","journal-title":"Fluids Barriers CNS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102222","DOI":"10.1016\/j.redox.2021.102222","article-title":"Role of glyoxalase 1 in methylglyoxal detoxification-the broad player of psychiatric disorders","volume":"49","author":"Toriumi","year":"2022","journal-title":"Redox Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nigro, C., Leone, A., Raciti, G.A., Longo, M., Mirra, P., Formisano, P., Beguinot, F., and Miele, C. 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