{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:41:49Z","timestamp":1786534909448,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Small- and Medium-sized Enterprises (SMEs) and Startups (MSS), Korea"},{"id":[{"id":"https:\/\/ror.org\/022c4zk48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Breast milk-derived lactic acid bacteria (LAB) are promising sources of functional postbiotics. In this study, we evaluated the immunomodulatory, epithelial barrier-enhancing, and anti-melanogenic properties of nonviable HUH02 preparations, including heat-killed cells (HUH02-HK) and microfluidized preparations generated at 20,000 psi (HUH02-2psi) and 40,000 psi (HUH02-4psi), derived from the breast milk-derived Lactobacillus paragasseri HUH02 (L. paragasseri HUH02). HUH02 derivatives were evaluated in RAW264.7 macrophages, HaCaT keratinocytes, and B16F1 melanoma cells. All exhibited low cytotoxicity at functional concentrations. In Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, HUH02 derivatives markedly reduced nitric oxide production and suppressed the expression of inflammatory mediators, restored macrophage morphology toward a non-activated phenotype, and reduced iNOS protein expression. In HaCaT keratinocytes, HUH02 derivatives enhanced wound closure and the expression of epithelial barrier-associated genes, including ZO-1 and Occludin. Moreover, microfluidized derivatives, particularly HUH02-2psi and HUH02-4psi, significantly enhanced transepithelial electrical resistance, indicating improved epithelial barrier integrity. In B16F1 melanoma cells, HUH02-derived preparations exhibited antimelanogenic effects by reducing intracellular melanin accumulation and suppressing the expression of melanogenesis-related genes and proteins, including Tyr, TRP-1, TRP-2, and MITF. HUH02 was identified as L. paragasseri based on 16S rRNA, average nucleotide identity, and whole-genome phylogenetic analyses. Genome-based safety assessment revealed the absence of antibiotic resistance genes, virulence factors, plasmid replicons, and pathogenicity-associated markers. These findings demonstrated that breast milk-derived L. paragasseri HUH02 postbiotics exhibit multifunctional biological activities, including immunomodulatory, epithelial barrier-enhancing, and antimelanogenic effects.<\/jats:p>","DOI":"10.3390\/microorganisms14081777","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:02:11Z","timestamp":1786532531000},"page":"1777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Characterization of Breast Milk-Derived Lactobacillus paragasseri HUH02 Postbiotic Preparations with Immunomodulatory, Skin Barrier-Protective, and Anti-Melanogenic Activities"],"prefix":"10.3390","volume":"14","author":[{"given":"Ran","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju 27475,  Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8660-2023","authenticated-orcid":false,"given":"Hyun-Chul","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Industry, Graduate School, Chungbuk National University, 194-21, Cheongju 26844, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-2411","authenticated-orcid":false,"given":"Chul-Sung","family":"Huh","sequence":"additional","affiliation":[{"name":"Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang 25354, Republic of Korea"},{"name":"Biodome Co., Wonju 26365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjoon","family":"Park","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon-Woo","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Animal Biotechnology, College of Life Science, Sangji University, Wonju 26339, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-1389","authenticated-orcid":false,"given":"Joo-Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"R&D Center, Dermalab Co., Ltd., #510 Ace Gwanggyo Tower 1, 17, Daehak 4-ro, Yeongtong-gu, Suwon-si 16226, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-1082","authenticated-orcid":false,"given":"Jun-Chul","family":"Kang","sequence":"additional","affiliation":[{"name":"R&D Center, Dermalab Co., Ltd., #510 Ace Gwanggyo Tower 1, 17, Daehak 4-ro, Yeongtong-gu, Suwon-si 16226, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-2052","authenticated-orcid":false,"given":"Hyun-Jung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju 27475,  Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s12602-025-10533-2","article-title":"Skin Protection Effects of Lactobacillus paragasseri HN910 Lysate and the Role of Alanine","volume":"18","author":"Lee","year":"2026","journal-title":"Probiot. 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