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To better understand the exact effects of real-life environmental conditions on the skin and determine the protective methods, this study investigates the effects of three topical cosmetic moisturizers (water gel moisturizers with\/without yeast extract (Moisturizers K and C) and a thick-emulsion cream moisturizer (Moisturizer L)) on clinical and skin microbiome endpoints in the presence of environmental aggressors during an 8-week, randomized controlled, triple-blind clinical trial with 110 participants, and molecular- as well as biomarker-level endpoints on ex vivo skin explants after exposure to simulate urban environmental conditions. The results show that all moisturizers are well-tolerated and improve skin barrier function and surface moisture content from the baseline, and the improvement is maintained at the last analysis point (3 days after trial completion). Compared with the untreated control areas (samples taken from the upper chest), treatment with Moisturizer K prevented a reduction in bacterial and fungal richness, and increased the change ratio of the relative abundance of commensal bacteria, such as Staphylococcus epidermidis and Ralstonia, at the treated sites (samples taken from the forehead). Moreover, Moisturizer K-treated ex vivo skin explants had higher levels of caspase 14 (a marker of skin barrier function), collagen I, and elastin (structure components), and lower levels of aryl hydrocarbon receptor (AHR; activated by air pollutants) and interleukin-6 (IL-6) than those in explants treated with other moisturizers and in the untreated areas of the skin. These results suggest that a skin postbiotic moisturizer with yeast extract supports the regulation of the skin\u2019s microbiome balance and may provide a holistic barrier (involving skin microbiome, physical, chemical, and immune barriers) to protect the skin against environmental aggressors.<\/jats:p>","DOI":"10.3390\/jcm12186078","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T22:38:45Z","timestamp":1695249525000},"page":"6078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effects of Investigational Moisturizers on the Skin Barrier and Microbiome following Exposure to Environmental Aggressors: A Randomized Clinical Trial and Ex Vivo Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Dan-Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Fudan Microbiome Center, Institute of Biodiversity Science, School of Life Sciences, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-2624","authenticated-orcid":false,"given":"Xi","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Science Asia Pacific, Shanghai Technology and Research Center, Johnson & Johnson (China) Ltd., Shanghai 200245, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Fudan Microbiome Center, Institute of Biodiversity Science, School of Life Sciences, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yuan","sequence":"additional","affiliation":[{"name":"Skin and Cosmetic Research Department, Shanghai Skin Disease Hospital, Shanghai 200443, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yan","sequence":"additional","affiliation":[{"name":"Translational Science Asia Pacific, Shanghai Technology and Research Center, Johnson & Johnson (China) Ltd., Shanghai 200245, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Humbert","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Clinical Investigation Center, Besancon University Hospital, 25030 Besancon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7561-8572","authenticated-orcid":false,"given":"Zhe-Xue","family":"Quan","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Fudan Microbiome Center, Institute of Biodiversity Science, School of Life Sciences, Fudan University, Shanghai 200437, China"},{"name":"IRDR ICoE on Risk Interconnectivity and Governance on Weather\/Climate Extremes Impact and Public Health, Fudan University, Shanghai 200437, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/ced.14353","article-title":"Literature mapping: Association of microscopic skin microflora and biomarkers with macroscopic skin health","volume":"46","author":"Li","year":"2021","journal-title":"Clin. 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