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Advances in sequencing technologies now facilitate detailed microbial profiling, driving intentional microbiome-targeted product development. Inspired by an academic-industry workshop held in January 2024, this review explores the oral, skin and gut microbiomes, focussing on the potential long-term implications of perturbations. Key challenges in microbiome safety assessment include confounding factors (ecological variability, host influences and external conditions like geography and diet) and biases from experimental measurements and bioinformatics analyses. The taxonomic composition of the microbiome has been associated with both health and disease, and perturbations like regular disruption of the dental biofilm are essential for preventing caries and inflammatory gum disease. However, further research is required to understand the potential long-term impacts of microbiome disturbances, particularly in vulnerable populations including infants. We propose that emerging technologies, such as omics technologies to characterize microbiome functions rather than taxa, leveraging artificial intelligence to interpret clinical study data and\n                    <jats:italic>in vitro<\/jats:italic>\n                    models to characterize and measure host\u2013microbiome interaction endpoints, could all enhance the risk assessments. The workshop emphasized the importance of detailed documentation, transparency and openness in computational models to reduce uncertainties. Harmonisation of methods could help bridge regulatory gaps and streamline safety assessments but should remain flexible enough to allow innovation and technological advancements. Continued scientific collaboration and public engagement are critical for long-term microbiome monitoring, which is essential to advancing safety assessments of microbiome perturbations.\n                  <\/jats:p>","DOI":"10.1099\/mgen.0.001405","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T07:15:56Z","timestamp":1747293356000},"source":"Crossref","is-referenced-by-count":15,"title":["Assessing the safety of microbiome perturbations"],"prefix":"10.1099","volume":"11","author":[{"given":"Aline","family":"Metris","sequence":"first","affiliation":[{"name":"Unilever, Safety, Environmental and Regulatory Sciences (SERS), Sharnbrook, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan W.","family":"Walker","sequence":"additional","affiliation":[{"name":"Microbiome, Food Innovation and Food Security Theme, Rowett Institute, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Showering","sequence":"additional","affiliation":[{"name":"BugBiome, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Doolan","sequence":"additional","affiliation":[{"name":"Atlantia Clinical Trials, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"McBain","sequence":"additional","affiliation":[{"name":"Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Ampatzoglou","sequence":"additional","affiliation":[{"name":"Unilever, Safety, Environmental and Regulatory Sciences (SERS), Sharnbrook, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Murphy","sequence":"additional","affiliation":[{"name":"Unilever R&D Port Sunlight, Bebington, Wirral, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"O'Neill","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Musculoskeletal Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Shortt","sequence":"additional","affiliation":[{"name":"Ulster University, Coleraine, NI BT52 1SA, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Darby","sequence":"additional","affiliation":[{"name":"Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Aldis","sequence":"additional","affiliation":[{"name":"Reckitt, Slough, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg G.","family":"Hillebrand","sequence":"additional","affiliation":[{"name":"University of Cincinnati, James L. 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