{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:49:07Z","timestamp":1782452947250,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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. Med."],"abstract":"<jats:p>\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    infection remains common worldwide and causes chronic gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Eradication therapy has become less reliable as resistance to clarithromycin, metronidazole, and levofloxacin has reduced the performance of older empiric regimens. Potassium-competitive acid blockers (P-CABs), molecular resistance testing, fecal susceptibility assays, and new antimicrobial strategies have changed treatment selection, but none removes the need to match regimen design to microbial biology and antibiotic activity. This narrative review argues that\n                    <jats:italic>H. pylori<\/jats:italic>\n                    management is shifting from empiric eradication toward mechanism-matched therapy. The framework links gastric niche biology, acid acclimation, adhesion, virulence signaling, immune evasion, resistance mechanisms, acid suppression, and partner-antibiotic selection. Recent randomized trials show the strengths and limits of this approach. Vonoprazan-based regimens improve acid suppression and can outperform proton pump inhibitor-based triple therapy in clarithromycin-resistant infection, but rescue-treatment trials show that potent acid suppression alone is insufficient when the partner antibiotic is poorly matched. Molecular testing-guided therapy and fecal molecular susceptibility testing provide practical ways to align antibiotic selection with resistance mechanisms. Rifasutenizol adds a pathogen-targeted option supported by phase 3 evidence in treatment-naive Chinese patients. Adjunctive and investigational approaches, including probiotics, vaccines, phytochemicals, phage-derived agents, and nanomedicine, should be interpreted as supportive or developmental strategies rather than replacements for validated antimicrobial regimens. A mechanism-matched approach can help clinicians and investigators choose regimens, interpret trial results, and design studies that distinguish failures caused by resistance, inadequate acid suppression, regimen intolerance, and prior antibiotic exposure.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1877827","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:43:48Z","timestamp":1782452628000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism-matched Helicobacter pylori treatment in the potassium-competitive acid blocker era"],"prefix":"10.3389","volume":"13","author":[{"given":"Akram","family":"Alnounou","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine","place":["Kalamazoo, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Martin","family":"Sieloff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine","place":["Kalamazoo, MI, United States"]},{"name":"Division of Gastroenterology, Bronson Methodist Hospital","place":["Kalamazoo, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1053\/j.gastro.2017.04.022","article-title":"Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis","volume":"153","author":"Hooi","year":"2017","journal-title":"Gastroenterology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1053\/j.gastro.2023.12.022","article-title":"Global prevalence of Helicobacter pylori infection and incidence of gastric cancer between 1980 and 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A three\u2010arm, multicenter randomized clinical trial","volume":"30","author":"Yu","year":"2025","journal-title":"Helicobacter"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/S1473-3099(24)00003-3","article-title":"Safety, pharmacokinetics, and efficacy of rifasutenizol, a novel dual-targeted antibacterial agent in healthy participants and patients in China with Helicobacter pylori infection: four randomised clinical trials","volume":"24","author":"Li","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"107600","DOI":"10.1016\/j.ijantimicag.2025.107600","article-title":"The impact of probiotics on Helicobacter pylori eradication with bismuth quadruple therapy: a systematic review and meta-analysis","volume":"66","author":"Liu","year":"2025","journal-title":"Int J Antimicrob Agents"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1016\/S0140-6736(15)60310-5","article-title":"Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"386","author":"Zeng","year":"2015","journal-title":"Lancet"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3787","DOI":"10.2147\/IDR.S412361","article-title":"How long will it take to launch an effective Helicobacter pylori vaccine for humans?","volume":"16","author":"Li","year":"2023","journal-title":"Infect Drug Resist"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1418129","DOI":"10.3389\/fmicb.2024.1418129","article-title":"Novel therapeutic regimens against Helicobacter pylori: an updated systematic review","volume":"15","author":"Huang","year":"2024","journal-title":"Front Microbiol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1652943","DOI":"10.3389\/fmicb.2025.1652943","article-title":"Therapeutic advances and future directions in Helicobacter pylori eradication","volume":"16","author":"Suresh","year":"2025","journal-title":"Front Microbiol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1877827\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:43:49Z","timestamp":1782452629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1877827\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":32,"alternative-id":["10.3389\/fmed.2026.1877827"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1877827","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]},"article-number":"1877827"}}