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Serving as a \u201csafe house\u201d for beneficial, desired gut bacteria, the appendix is protected by resilient biofilms that create a secure environment. This makes the appendix a\u201dbasin\u201d for gut microbiota (GM), replenishing the microbial population following disruptions from infections, antibiotic use, or inflammatory bowel disease (IBD). Beyond simply hosting bacteria, the appendix has an active role in functions of the immune system. Disruption of the Appendix Microbiome (AM), such as through appendectomy, was found to result in lowered diversity of gut microorganisms and an increased risk of various diseases. The potential therapeutic applications of the AM are a particularly promising area of research. The appendix\u2019s unique microbial environment and its impact on immunity open new avenues for treatments. These include modulating GM to improve cancer treatment outcomes, mitigating IBD, regulating metabolic pathways in obesity and diabetes, influencing neurotransmitter production in neurological disorders, and addressing cardiovascular and autoimmune diseases. This review highlights the appendix\u2019s transformation from a misunderstood organ to a critical component of gut health and immunity. It explores the function of the human appendix as a resilient reservoir for desired microorganisms, and its role in disease progression. Furthermore, it examines the potential therapeutic applications of AM, presenting exciting opportunities for future research and treatment innovations.<\/jats:p>","DOI":"10.1186\/s13099-025-00696-2","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T13:53:38Z","timestamp":1748786018000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The functional landscape of the appendix microbiome under conditions of health and disease"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-4369","authenticated-orcid":false,"given":"Md Shahjalal","family":"Sagor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-7685","authenticated-orcid":false,"given":"Tarequl","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noshin Tabassum","family":"Tamanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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