{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:17:39Z","timestamp":1791908259735,"version":"4.3.4"},"reference-count":54,"publisher":"Akademiai Kiado Zrt.","issue":"2","funder":[{"name":"Research Project Plan of the Health Commission of Jinshan District, Shanghai","award":["JSKJ-KTMS-2023-08"],"award-info":[{"award-number":["JSKJ-KTMS-2023-08"]}]}],"content-domain":{"domain":["www.akjournals.com"],"crossmark-restriction":true},"short-container-title":["AMICR"],"published-print":{"date-parts":[[2026,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To evaluate the effect of montelukast combined with inhaled corticosteroids (ICS) on the microbiome-metabolism-immunity axis in children with asthma and to quantify the mediating role of short-chain fatty acids, this single-center, randomized controlled trial enrolled 100 asthmatic children (aged 6\u201311) who received inhaled corticosteroids with or without montelukast for 12 weeks (\n                    <jats:italic>n<\/jats:italic>\n                    = 50 in the combination group and\n                    <jats:italic>n<\/jats:italic>\n                    = 50 in the ICS-alone group). Microbiome profiles from nasal and fecal samples were assessed via 16S sequencing, and short-chain fatty acids (SCFAs) were quantified by LC-MS\/MS. Immune markers (Tregs, cytokines) were measured by flow cytometry and Bio-Plex. Efficacy analyses employed linear mixed-effects models, and SCFA mediation was tested using bootstrap analysis. The combination group demonstrated significantly greater improvements in clinical outcomes including fractional exhaled nitric oxide (FeNO) (\u03b2_int = \u221210.24\u2009ppb, 95% CI \u221216.37 to \u22124.11,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.001), Childhood Asthma Control Test (C-ACT) score (\u03b2_int = +1.83,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05) and FEV1% (\u03b2_int = +1.87,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05) compared to ICS alone. Microbiome analysis revealed enhanced \u03b1-diversity in both nasal and fecal samples (interaction\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01) with significant community structure changes (PERMANOVA interaction P_perm &lt; 0.01). Specific genus-level alterations included reduced nasal Moraxella and Haemophilus (logFC &lt; 0,\n                    <jats:italic>q<\/jats:italic>\n                    &lt; 0.10) and increased fecal SCFA-producing taxa including Faecalibacterium, Roseburia, Subdoligranulum, Agathobacter, and\n                    <jats:italic>Eubacterium hallii<\/jats:italic>\n                    group (logFC &gt; 0,\n                    <jats:italic>q<\/jats:italic>\n                    &lt; 0.10). The combination therapy also led to elevated fecal and serum SCFA levels (\u03b2_int &gt; 0,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01), enhanced regulatory T cell (Treg) and IL-10 responses, and suppressed Th2 cytokines (IL-4\/IL-5\/IL-13). Mediation analysis confirmed SCFAs partially mediated FeNO improvement, with proportions of 30.0% for total SCFAs and 37.5% for butyrate (ACME and ADE both negative,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01). The combination of montelukast and inhaled corticosteroids was superior to inhaled corticosteroids alone, providing clinical benefits that were linked to favorable remodeling of the airway-gut microbiome and enhanced Treg\/IL-10 immunity. This improvement was partially mediated by short-chain fatty acids, with a comparable safety profile.\n                  <\/jats:p>","DOI":"10.1556\/030.2026.02777","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:20:47Z","timestamp":1770024047000},"page":"223-234","update-policy":"https:\/\/doi.org\/10.1556\/policypage.crossmark.crossref.2","source":"Crossref","is-referenced-by-count":2,"title":["Effects of montelukast combined with inhaled corticosteroids on the airway\u2013gut microbiome and immune regulation in children with asthma"],"prefix":"10.1556","volume":"73","author":[{"given":"DianBiao","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Jinshan Branch of Shanghai Sixth People's Hospital (Jinshan Central Hospital affiliated to Shanghai University of Medicine & Health Sciences), Shanghai, 201599, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YueJin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jinshan Branch of Shanghai Sixth People's Hospital (Jinshan Central Hospital affiliated to Shanghai University of Medicine & Health Sciences), Shanghai, 201599, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YuLi","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jinshan Branch of Shanghai Sixth People's Hospital (Jinshan Central Hospital affiliated to Shanghai University of Medicine & Health Sciences), Shanghai, 201599, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HanYing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jinshan Branch of Shanghai Sixth People's Hospital (Jinshan Central Hospital affiliated to Shanghai University of Medicine & Health Sciences), Shanghai, 201599, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"425","reference":[{"issue":"1","key":"B1","series-title":"Ann Glob Health","doi-asserted-by":"publisher","first-page":"6","DOI":"10.5334\/aogh.2416","article-title":"Pediatric asthma: a global epidemic","volume":"85","author":"Serebrisky D","year":"2019","unstructured":"Serebrisky D, Wiznia A. 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