{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:36:39Z","timestamp":1785429399552,"version":"3.56.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"the Inner Mongolia Autonomous Region Science and Technology Leading Talent Team Project","award":["No.2022LJRC0003"],"award-info":[{"award-number":["No.2022LJRC0003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. U22A20540"],"award-info":[{"award-number":["No. U22A20540"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["No. 2022YFD2100700"],"award-info":[{"award-number":["No. 2022YFD2100700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Earmarked Fund for China Agriculture Research System","award":["CARS-36"],"award-info":[{"award-number":["CARS-36"]}]},{"name":"the China National Postdoctoral Program for Innovative Talents","award":["BX20250337"],"award-info":[{"award-number":["BX20250337"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2026,2,17]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Proton pump inhibitors (PPIs) are standard therapy for gastroesophageal reflux disease (GERD), but long-term use causes dysbiosis, gastrointestinal side effects, and symptom relapse after discontinuation. Probiotics may offer adjunctive benefits by modulating the gut ecosystem. The study aimed to evaluate the efficacy of a multi-strain probiotic (Lihuo) with rabeprazole in GERD and its impact on gut microbiota and metabolome. A randomized, double-blind, placebo-controlled trial was conducted in 120 GERD patients assigned to receive rabeprazole with either Lihuo (\n n<\/jats:italic>\n = 64) or placebo (\n n<\/jats:italic>\n = 56) for 8 weeks, followed by 4 weeks of probiotic or placebo alone. The primary outcome was change in the Reflux Disease Questionnaire (RDQ) score. Secondary outcomes included Gastrointestinal Symptom Rating Scale, endoscopic healing, and multi-omics profiling (shotgun metagenomics, phageome, and untargeted\/targeted metabolomics). Compared with the placebo group, the probiotic group exhibited a pronounced 36.51% reduction in RDQ scores after 12 weeks of intervention (\n P<\/jats:italic>\n = 0.017), alongside a higher numerical endoscopic healing rate (36.84% vs 12.50%;\n P<\/jats:italic>\n = 0.365). Metagenomics revealed enrichment of\n Bifidobacterium animalis<\/jats:italic>\n ,\n Lactiplantibacillus plantarum<\/jats:italic>\n , and\n Clostridium<\/jats:italic>\n sp900540255, with reductions in\n Bacteroides uniformis<\/jats:italic>\n and\n Clostridium<\/jats:italic>\n Q\n fessum<\/jats:italic>\n . Metabolomics showed increased \u03b3-aminobutyric acid, succinate, citrulline, and short-chain fatty acids levels, with interesting microbe-metabolite correlations such as\n Bifidobacterium animalis<\/jats:italic>\n -\u03b3-aminobutyric acid and\n Bacteroides fragilis<\/jats:italic>\n -succinate (\n r<\/jats:italic>\n \u2265 0.30,\n P<\/jats:italic>\n < 0.01). Our findings support that adjunctive probiotic therapy sustains post-PPI symptom relief, associated with targeted modulation of gut microbiota and bioactive metabolites.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Long-term proton pump inhibitor use in gastroesophageal reflux disease (GERD) may disrupt gut microbiota and cause symptom relapse after discontinuation. We found that adjunctive probiotic therapy sustained reflux reduction post-proton pump inhibitor. Probiotic use enriched beneficial taxa (\n Bifidobacterium<\/jats:italic>\n and\n Lactiplantibacillus plantarum<\/jats:italic>\n ) and increased \u03b3-aminobutyric acid, succinate, citrulline, and short-chain fatty acids. Strong correlations linked microbial shifts to metabolic and clinical improvements. This study demonstrates that adjunctive probiotic therapy enhances symptom control and supports microbial-metabolic homeostasis in GERD.\n <\/jats:p>\n <\/jats:sec>\n \n CLINICAL TRIALS<\/jats:title>\n \n This study is registered with the Chinese Clinial Trial Registry as\n ChiCTR2000038409<\/jats:related-object>\n .\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/msystems.01568-25","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T14:00:27Z","timestamp":1769695227000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Adjunctive probiotic therapy sustains symptom relief in gastroesophageal reflux disease through gut microbiome-metabolome remodeling"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-2448","authenticated-orcid":true,"given":"Yingmeng","family":"Li","sequence":"first","affiliation":[{"name":"Inner Mongolia 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