{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:38:55Z","timestamp":1792363135486,"version":"4.4.0"},"reference-count":103,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002382","name":"King Faisal Specialist Hospital and Research Centre","doi-asserted-by":"publisher","award":["RAC# 2240005"],"award-info":[{"award-number":["RAC# 2240005"]}],"id":[{"id":"10.13039\/501100002382","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RAC# 2240005"],"award-info":[{"award-number":["RAC# 2240005"]}],"id":[{"id":"https:\/\/ror.org\/05n0wgt02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although human mammary glands were traditionally considered sterile, accumulating evidence has established the presence of distinct microbial communities that may have colonized breast tissue primarily via retrograde nipple flow or via hematogenous or lymphatic translocation from other body sites. Comparative studies reveal differences in the microbiota of healthy and diseased breast tissues, with variations in microbial signatures across breast cancer subtypes and in comparison with adjacent normal tissues. This review synthesizes current evidence on the composition of the breast microbiome, the factors shaping its development, and alterations it undergoes in inflammatory and malignant breast diseases. Furthermore, the article discusses mechanistic insights, methodological challenges, and future therapeutic perspectives based on published studies employing culture-independent approaches, such as 16S rRNA gene sequencing and metagenomic analyses. Key host-related factors influencing breast-associated microbial communities, including hormonal regulation, environmental exposure, diet, and therapeutic interventions, are explored. The existing literature is assessed to identify key associations between the breast microbiome and host signaling pathways, as well as the significant challenges that remain unresolved, including low biomass contamination, inter-study variability, limited longitudinal data, and an incomplete understanding of causality. Addressing these limitations is critical for advancing microbiome-based diagnostic and therapeutic strategies for breast disease.<\/jats:p>","DOI":"10.3390\/ijms27114723","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:45:08Z","timestamp":1779673508000},"page":"4723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Human Breast Microbiome: From Homeostasis to Malignancy, Mechanistic Insights and Therapeutic Perspectives"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-691X","authenticated-orcid":false,"given":"Mysoon M.","family":"Al-Ansari","sequence":"first","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Innovation and Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suha M.","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Innovation and Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2150-5297","authenticated-orcid":false,"given":"Monther","family":"Al-Alwan","sequence":"additional","affiliation":[{"name":"Innovation and Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia"},{"name":"College of Medicine, Al-Faisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1021\/acs.chemrev.2c00431","article-title":"Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies","volume":"123","author":"Aggarwal","year":"2023","journal-title":"Chem. 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