{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:01:45Z","timestamp":1790805705968,"version":"4.1.0"},"reference-count":151,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The human gut microbiome comprises a diverse community of bacteria whose interactions with the host range from beneficial mutualism to opportunistic pathogenicity. These interactions are shaped by genomic plasticity and ecological pressures that influence whether microbes support host health, remain conditionally harmless, or contribute to disease. Understanding the mechanisms underlying these shifts is essential for clarifying the balance between cooperation and pathogenicity within the gut ecosystem. This review explores the genomic and evolutionary mechanisms that shape microbial adaptation across the mutualism\u2013pathogenicity spectrum in the human gut. Key processes, including horizontal gene transfer (HGT), host-mediated selection, and niche specialization, enable microbes to acquire, regulate, or retain traits that influence colonization, metabolic function, and virulence. These adaptive mechanisms allow gut bacteria to respond dynamically to ecological pressures such as inflammation, antibiotic exposure, and dietary change, resulting in context-dependent microbial behaviors. The review also considers how concepts from insect endosymbiosis may provide insight into gut microbial adaptation. While both systems exhibit host specialization, major differences in transmission mode, ecological flexibility, and genome evolution limit direct comparisons. Rather than following a fixed progression toward parasitism, gut microbes exhibit flexible adaptive strategies shaped by host and environmental conditions. By integrating ecological and evolutionary perspectives, this review presents a balanced framework for understanding how genomic adaptation influences microbial behavior in the gut. This perspective improves our understanding of dysbiosis and microbial pathogenesis and may support the development of microbiome-informed therapeutic strategies for maintaining host health.<\/jats:p>","DOI":"10.3390\/ijms27115009","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"5009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evolutionary Genomics of Human Gut Bacteria: Ecological Plasticity Across the Mutualism\u2013Pathogenicity Spectrum"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7374-9334","authenticated-orcid":false,"given":"Yasmin N.","family":"Ramadan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8025-5454","authenticated-orcid":false,"given":"Salwa Q.","family":"Bukhari","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine, University of Tabuk, Tabuk 47512, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8963-8398","authenticated-orcid":false,"given":"Zinab","family":"Alatawi","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, Faculty of Medicine, University of Tabuk, Tabuk 47512, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaleb","family":"Oriquat","sequence":"additional","affiliation":[{"name":"Faculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura H. Abd","family":"Ellah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eltayib Hassan Ahmad","family":"Mohamedosman","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Science, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2476-469X","authenticated-orcid":false,"given":"Rehab","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8541-7304","authenticated-orcid":false,"given":"Helal F.","family":"Hetta","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3390\/immuno4040026","article-title":"Gut Microbiome as a Target of Intervention in Inflammatory Bowel Disease Pathogenesis and Therapy","volume":"4","author":"Hetta","year":"2024","journal-title":"Immuno"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41579-021-00550-7","article-title":"Microbial evolution and transitions along the parasite-mutualist continuum","volume":"19","author":"Drew","year":"2021","journal-title":"Nat. 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