{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:52:54Z","timestamp":1793055174984,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Refractory asthma in children remains a clinical challenge despite conventional therapies, with emerging evidence linking gut microbiome dysbiosis to persistent inflammation via the gut-lung axis. This study investigated whether multi-strain probiotic supplementation could improve asthma control and restore microbial balance when added to standard treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective randomized controlled trial enrolled 88 children aged 4\u20138\u202fyears with refractory asthma. Participants were allocated into two groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f44 each): a conventional treatment group (bronchodilators and glucocorticoids) and a combination treatment group, which received conventional therapy plus a multi-strain probiotic (\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      ,\n                      <jats:italic>Lactobacillus acidophilus<\/jats:italic>\n                      ,\n                      <jats:italic>Streptococcus thermophilus<\/jats:italic>\n                      ) for 4\u202fmonths. Primary outcomes were asthma control level, Asthma Control Test (ACT) scores, and pulmonary function (FEV\u2081, FVC, PEF). Secondary outcomes included gut microbiota changes, assessed by 16S rRNA gene sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Combination therapy achieved complete asthma control in 68.18% of patients versus 36.36% with conventional therapy (\n                      <jats:italic>Z<\/jats:italic>\n                      \u202f=\u202f2.415,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). Post-treatment ACT scores were higher in the combination group (22.45\u202f\u00b1\u202f1.20 vs. 19.78\u202f\u00b1\u202f1.45;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05), with superior improvements in FEV1 (2.65\u202f\u00b1\u202f0.10\u202fL vs. 2.30\u202f\u00b1\u202f0.08\u202fL;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), FVC (3.10\u202f\u00b1\u202f0.18\u202fL vs. 2.80\u202f\u00b1\u202f0.15\u202fL;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), and PEF (4.00\u202f\u00b1\u202f0.25\u202fL\/s vs. 3.50\u202f\u00b1\u202f0.20\u202fL\/s; p\u202f&amp;lt;\u202f0.001). Symptoms resolved faster with combination therapy (e.g., cough: 5.60\u202f\u00b1\u202f1.50 vs. 10.45\u202f\u00b1\u202f2.30\u202fdays;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). Microbiome analysis showed increased alpha diversity (e.g., Shannon index:\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05) and beneficial shifts in the combination group, including higher Bifidobacterium (25.00\u202f\u00b1\u202f15.31% vs. 0.98\u202f\u00b1\u202f1.92%;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) and reduced Bacteroides, with distinct beta diversity clustering (PERMANOVA\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Adjunctive multi-strain probiotics enhance clinical outcomes and gut microbiome health in pediatric refractory asthma, supporting microbiome-targeted therapies via the gut-lung axis. Larger, double-blind randomized controlled trials are warranted to confirm long-term benefits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1756436","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T06:59:51Z","timestamp":1770793191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Probiotic supplementation modulates the gut microbiome and improves clinical outcomes in pediatric refractory asthma"],"prefix":"10.3389","volume":"17","author":[{"given":"Zheng","family":"Liu","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents Health and Diseases, Ministry of Education, Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Jiangxi Children\u2019s Medical Center","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Jiangxi Children\u2019s Medical Center","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Jiangxi Children\u2019s Medical Center","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Jiangxi Children\u2019s Medical Center","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref1","first-page":"PA4507","volume-title":"Gut microbiota in wheezing preschool children and the development of childhood asthma, in Paediatric asthma and allergy","author":"Bannier","year":"2019"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.immuni.2020.01.007","article-title":"The role of lung and gut microbiota in the pathology of asthma","volume":"52","author":"Barcik","year":"2020","journal-title":"Immunity"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1080\/1744666X.2023.2189103","article-title":"Probiotics in asthma management: fiction or truth?","volume":"19","author":"Ciprandi","year":"2023","journal-title":"Expert Rev. 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