{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:07:48Z","timestamp":1784092068454,"version":"3.55.0"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","award":["WAQF:00057671-141-2026"],"award-info":[{"award-number":["WAQF:00057671-141-2026"]}],"id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dominant anti-infective strategies equate therapeutic success with pathogen eradication, yet in the gut most clinically relevant \u201cpathogens\u201d are pathobionts that cause disease only under specific ecological conditions. Antibiotics resolve infection but decimate commensal communities and select for resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Scope and approach<\/jats:title>\n                    <jats:p>We review antibody-based interventions, native mucosal antibodies (IgA, IgM), monoclonal antibodies, and immunoglobulin Y (IgY), as mechanistic test cases for a functional silencing paradigm, in which pathobiont virulence is attenuated through non-bactericidal mechanisms while preserving community architecture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>\n                      Drawing on randomized trial data (bezlotoxumab in\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      recurrence prevention, MODIFY I\/II, n = 2,655), preclinical and early clinical IgY studies in enteric infections, and long-term IgY deployment in aquaculture, we find that functional silencing delivers durable benefit when disease is driven by discrete virulence factors. However, evolutionary risks, including phase variation, conformational switching, and the theoretical framework of \u201cimperfect immunity\u201d, identify conditions under which retained pathobionts may re-emerge as threats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Eradication and functional silencing are best understood as complementary strategies whose optimal deployment depends on host immune status, barrier integrity, and the nature of pathobiont virulence. Defining the boundary between safe coexistence and evolutionary rebound constitutes the field\u2019s central unresolved challenge.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1903103","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:39:29Z","timestamp":1784090369000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Coexist or eliminate? Antibody-based functional silencing versus eradication in gut microbiome- targeted therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Sherif A.","family":"El-Kafrawy","sequence":"first","affiliation":[{"name":"Special Infectious Agents Unit-Biosafety Level 3 (BSL3), King Fahd Medical Research Center, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman T.","family":"Abbas","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-Biosafety Level 3 (BSL3), King Fahd Medical Research Center, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman S.","family":"El-Kafrawy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Menoufia University","place":["Shebin El-Koam, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai M.","family":"El-Daly","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-Biosafety Level 3 (BSL3), King Fahd Medical Research Center, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esam I.","family":"Azhar","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-Biosafety Level 3 (BSL3), King Fahd Medical Research Center, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1177\/20499361231154443","article-title":"Current understanding of antibiotic-associated dysbiosis and approaches for its management","volume":"10","author":"Kesavelu","year":"2023","journal-title":"Ther Adv Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.572912","article-title":"Antibiotics as major disruptors of gut microbiota","volume":"10","author":"Ramirez","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2536","article-title":"Shifting the balance: antibiotic effects on host-microbiota mutualism","volume":"9","author":"Willing","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0261-1","article-title":"Rethinking mucosal antibody responses: Igm, Igg and Igd join Iga","volume":"20","author":"Chen","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j5145","article-title":"The role of the gut microbiome in systemic inflammatory disease","volume":"360","author":"Clemente","year":"2018","journal-title":"BMJ (Clinical Res Ed)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.02.009","article-title":"Microbiota-antibody interactions that regulate gut homeostasis","volume":"29","author":"Weis","year":"2021","journal-title":"Cell Host Microbe"},{"key":"B7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002533","article-title":"Revised estimates for the number of human and bacteria cells in the body","volume":"14","author":"Sender","year":"2016","journal-title":"PloS Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7010014","article-title":"What is the healthy gut microbiota composition? 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