{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:28:42Z","timestamp":1785338922263,"version":"3.55.0"},"reference-count":154,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inflammatory bowel disease (IBD) represents a chronic relapsing disorder driven by a loss of homeostatic balance between the host immune system and the intestinal microbiota. Endogenous antimicrobial peptides (AMPs), produced primarily by epithelial and immune cells, function in concert with commensal microorganisms to preserve mucosal integrity and barrier function. Disruption of this antimicrobial equilibrium\u2014through genetic susceptibility such as NOD2 mutations or environmental perturbations including antibiotic overuse\u2014can impair antimicrobial defense, distort microbial composition, and initiate chronic inflammation. Recent investigations have revealed distinct alterations in AMP expression across IBD subtypes. In Crohn\u2019s disease, Paneth cell\u2013derived \u03b1-defensins (HD5 and HD6) are markedly diminished in the ileal mucosa, whereas colonic, segmental IBD exhibits inadequate induction of \u03b2-defensins and LL-37. Conversely, in actively inflamed regions, certain AMPs such as human \u03b2-defensin-2 (HBD2) and lysozyme are strongly upregulated, reflecting a compensatory response to inflammatory cell infiltration and microbial invasion. Beyond host-derived peptides, broad-spectrum antibiotic exposure profoundly reshapes commensal communities, attenuates basal pattern-recognition receptor signaling, and secondarily perturbs AMP regulation\u2014creating a feedback loop that amplifies dysbiosis. Here, we conceptualize these interactions as an integrated AMP\u2013antibiotic\u2013microbiota triad, in which endogenous antimicrobial regulation, exogenous antimicrobial pressure, and microbial ecological resilience dynamically co-determine mucosal stability. By positioning AMPs within this tripartite regulatory framework, this review delineates how antimicrobial imbalance arises across IBD subtypes, compares emerging therapeutic strategies\u2014including AMP enhancement, microbiota-sparing antibiotic regimens, fecal microbiota transplantation, and metabolite-guided interventions\u2014and highlights implications for precision recalibration of antimicrobial homeostasis in IBD.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1779550","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:16:53Z","timestamp":1773757013000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The AMP\u2013antibiotic\u2013microbiota triad in IBD: a mechanistic framework for dysregulated antimicrobial defense"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuyuan","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Colorectal Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaobo","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune 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