{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:54:29Z","timestamp":1775804069891,"version":"3.50.1"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"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. Pediatr."],"abstract":"\n Objectives and study<\/jats:title>\n \n To explore the effects and mechanisms of lactoferrin combined with\n Bifidobacterium animalis<\/jats:italic>\n subsp.\n lactis<\/jats:italic>\n BB-12 on Respiratory tract infections (RTIs) in healthy children through a randomized, double-blind, placebo-controlled trial.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Eligible healthy children aged 0\u20136 years were randomized into intervention group (IG,\n n<\/jats:italic>\n \u2009=\u200960, receiving lactoferrin and probiotic for 3 months) and control group (CG,\n n<\/jats:italic>\n \u2009=\u200934, receiving placebo). The study primarily assessed changes in the incidence and severity of RTIs, and monitored gastrointestinal adverse events. Fecal samples were collected pre- and post-intervention to analyze gut microbiota composition and metabolomic profiles, including short-chain fatty acids (SCFAs).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After the intervention, the incidence of RTIs showed no significant difference between groups (55% vs. 61.8%,\n p<\/jats:italic>\n \u2009=\u20090.52), but both the RTI severity score (3.0 vs. 4.0,\n p<\/jats:italic>\n \u2009&lt;\u20090.05) and mean duration per RTI episode (3.54 d vs. 5.27 d,\n p<\/jats:italic>\n \u2009&lt;\u20090.05) were significantly lower in the IG. No serious adverse events were reported, and the incidence of indigestion was significantly reduced in the IG compared with the CG (8.3% vs. 23.5%,\n p<\/jats:italic>\n \u2009=\u20090.04). The intervention significantly altered phylogenetic diversity (PD-whole tree within IG:\n p<\/jats:italic>\n \u2009=\u20090.0011; baseline between IG and CG:\n p<\/jats:italic>\n \u2009=\u20090.63; post-intervention between IG and CG:\n p<\/jats:italic>\n \u2009=\u20090.029) and community structure (weighted UniFrac within IG: 0.012; between IG and CG at 3 months:\n p<\/jats:italic>\n \u2009=\u20090.036 vs. baseline\n p<\/jats:italic>\n \u2009=\u20090.01). The gut microbiota in the intervention group exhibited a trend toward greater stability over time. Integrated microbiome\u2013metabolite analysis showed attenuation of fatty acid oxidation\u2013and energy metabolism-related metabolic drivers after intervention, together with no significant changes in fecal SCFA levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The intervention improved clinical outcomes and induced phylogenetic restructuring of the gut microbiota rather than changes in overall abundance, accompanied by a shift toward greater stability in gut microbial structure and energy metabolic patterns.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n identifier ChiCTR2500111308.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fped.2026.1778240","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:59:12Z","timestamp":1775800752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactoferrin combined with Bifidobacterium animalis subsp. lactis BB-12 improves respiratory tract infections and modulates Gut microbiome function in children: a randomized, double-blind, placebo-controlled trial"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhe","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huajiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Public Health, Shanghai Pudong New Area Shuyuan Community Health Service Center","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohan","family":"Tao","sequence":"additional","affiliation":[{"name":"H&H Group, China Research and Innovation Center","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feitong","family":"Liu","sequence":"additional","affiliation":[{"name":"H&H Group, China Research and Innovation Center","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Zhao","sequence":"additional","affiliation":[{"name":"H&H Group, China Research and Innovation Center","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of 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