{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:00:32Z","timestamp":1780898432368,"version":"3.54.1"},"reference-count":79,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"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>Systemic antibiotics are among the most widely prescribed therapeutic agents worldwide, and their effects on host\u2013microbe equilibrium extend well beyond the infection for which they are intended. Periodontitis is conventionally framed as a biofilm-initiated, host-mediated inflammatory disease, although recent work has shifted this framework toward microbial homeostasis as a regulator of periodontal stability. We hypothesize that antibiotics are not direct etiologic agents of periodontitis but instead act as risk-modifying factors that lower the threshold at which plaque-mediated inflammation progresses to destructive disease. We propose that this effect may operate through several mechanisms: broad-spectrum or repeated exposure could deplete protective commensals and narrow microbial diversity, creating ecological space for opportunistic and pathogenic taxa; antibiotics may also alter host neutrophil function, cytokine profiles, and antimicrobial peptide regulation and may interfere with the osteoblastic and osteoclastic dynamics governing alveolar bone remodelling; and antibiotic-induced gut dysbiosis may propagate systemic inflammatory signals that further modulate periodontal susceptibility. To evaluate this hypothesis, we synthesize the available clinical, epidemiological, and experimental data across four converging axes\u2014oral microbial ecology, immune regulation, alveolar bone remodelling, and the gut\u2013oral axis\u2014and identify the predictions the hypothesis generates and the evidence gaps it exposes. We emphasize that no clinical study has yet demonstrated a causal link between antibiotic exposure and periodontitis; the framework advanced here is therefore intended to inform antimicrobial stewardship in dentistry and to define a research agenda for determining whether antibiotic exposure constitutes a clinically meaningful modifier of periodontal disease susceptibility.<\/jats:p>","DOI":"10.3390\/ijms27125150","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:43:46Z","timestamp":1780897426000},"page":"5150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibiotic Exposure and Periodontal Susceptibility: A Risk-Modifying Hypothesis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-2768","authenticated-orcid":false,"given":"Nada Tawfig","family":"Hashim","sequence":"first","affiliation":[{"name":"Department of Periodontics, RAK College of Dental Sciences, RAK Medical & Health Sciences University, Ras-AlKhaimah 12973, United Arab Emirates"},{"name":"Department of Oral Rehabilitation, Faculty of Dentistry, University of Khartoum, Khartoum 11115, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nallan C. S. K.","family":"Chaitanya","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Radiology, RAK College of Dental Sciences, RAK Medical & Health Sciences University, Ras-AlKhaimah 12973, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-2033","authenticated-orcid":false,"given":"Rasha","family":"Babiker","sequence":"additional","affiliation":[{"name":"Department of Physiology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras-AlKhaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Implantology, Nile University, Khartoum 11115, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed Mustahsen","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Periodontics, RAK College of Dental Sciences, RAK Medical & Health Sciences University, Ras-AlKhaimah 12973, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-6245","authenticated-orcid":false,"given":"Riham","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, RAK College of Dental Sciences, RAK Medical & Health Sciences University, Ras-AlKhaimah 12973, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Preventive Dentistry, RAK College of Dental Sciences, RAK Medical & Health Sciences University, Ras-AlKhaimah 12973, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0604-9553","authenticated-orcid":false,"given":"Md Sofiqul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Operative Dentistry, RAK College of Dental Sciences, RAK Medical and Health Sciences University, Ras-AlKhaimah 12973, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Elsheikh","sequence":"additional","affiliation":[{"name":"Department of Oral &Maxillofacial Surgery, Faculty of Dentistry, University of Khartoum, Khartoum 11115, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5587-4050","authenticated-orcid":false,"given":"Salma Musa Adam","family":"Abduljalil","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dentistry, National University, Khartoum 11115, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakri Gobara","family":"Gismalla","sequence":"additional","affiliation":[{"name":"Department of Oral Rehabilitation, Faculty of Dentistry, University of Khartoum, Khartoum 11115, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"El Bahra","sequence":"additional","affiliation":[{"name":"Clinical Sciences Department, College of Dentistry, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E3463","DOI":"10.1073\/pnas.1717295115","article-title":"Global increase and geographic convergence in antibiotic consumption between 2000 and 2015","volume":"115","author":"Klein","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41368-022-00212-1","article-title":"Systemic antibiotics increase microbiota pathogenicity and oral bone loss","volume":"15","author":"Yuan","year":"2023","journal-title":"Int. J. Oral Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jdsr.2022.10.002","article-title":"Macrophages in periodontitis: A dynamic shift between tissue destruction and repair","volume":"58","author":"Yin","year":"2022","journal-title":"Jpn. 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