{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:49:22Z","timestamp":1790624962065,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"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. Nutr."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aimed to examine the effects of <jats:italic>Bifidobacterium longum subsp. infantis<\/jats:italic> YLGB-1496 (<jats:italic>B. infantis<\/jats:italic> YLGB-1496) on the frequency of respiratory illness symptoms and immunity profiles among toddlers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this double-blind, randomized, placebo-controlled, 12-week intervention study, toddlers with at least 2 respiratory illness symptoms were randomly assigned into the probiotic (YLGB-1496) or placebo group at a 1:1 ratio. Follow-up examinations were conducted at baseline (week 0) and at weeks 6 and 12 of the intervention. The frequency of respiratory illness symptoms was assessed at these time points using validated questionnaires. Oral swabs and fecal samples were collected from participants at weeks 0, 6, and 12 to examine inflammatory cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 120 toddlers initially included in the study, 115 completed the 12-week intervention (58 in the YLGB-1496 group and 57 in the placebo group). The risk of antibiotic use or clinical visits was significantly lower in the YLGB-1496 group than in the placebo group (antibiotic use odds ratio (OR)\u202f=\u202f0.37 [0.369, 0.372]; clinical visit, OR\u202f=\u202f0.743 [0.741, 0.744]), but these differences were nonsignificant after adjusting for other potential confounders (<jats:italic>p<\/jats:italic>\u202f&amp;gt;\u202f0.05). The YLGB-1496 group presented a lower incidence of several respiratory symptoms than the placebo group, including fever (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), cough (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), sneezing (<jats:italic>p<\/jats:italic>\u202f=\u202f0.012), nose block (<jats:italic>p<\/jats:italic>\u202f=\u202f0.001), and runny nose (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). The results also revealed that the salivary cortisol concentration was significantly lower in the YLGB-1496 group than in the placebo group (<jats:italic>p<\/jats:italic>\u202f=\u202f0.026), but no effects on INF-<jats:italic>\u03b3<\/jats:italic>, IL-1\u03b2, IL-13, IL-4, or IL-10 were detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Bifidobacterium infantis<\/jats:italic> YLGB-1496 may serve as a potential natural, nonpharmacological strategy for the safe management of respiratory tract issues in toddlers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>The trial was registered at <jats:uri>ClinicalTrials.gov<\/jats:uri> (identifier number NCT05794815).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1537610","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:13:36Z","timestamp":1739942016000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical effects of Bifidobacterium Longum Subsp. Infantis YLGB-1496 on children with respiratory symptoms"],"prefix":"10.3389","volume":"12","author":[{"given":"Pin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Mageswary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adli","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahisham","family":"Taib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thai Hau","family":"Koo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azianey","family":"Yusof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanglian","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilian","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Tze","family":"Liong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1126\/science.147.3659.747","article-title":"Probiotics: growth-promoting factors produced by microorganisms","volume":"147","author":"Lilly","year":"1965","journal-title":"Science (New York, NY)"},{"key":"ref2","year":"2001"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3390\/nu12061581","article-title":"Bifidobacterium longum subspecies infantis (B. infantis) in pediatric nutrition: current state of knowledge","volume":"12","author":"Chichlowski","year":"2020","journal-title":"Nutrients"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.20960\/nh.04315","article-title":"Bifidobacterium longum subsp. infantis CECT 7210 (B. infantis IM-1\u00ae) shows activity against intestinal pathogens","volume":"39","author":"Moreno-Mu\u00f1oz","year":"2022","journal-title":"Nutr Hosp"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk1107","article-title":"Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition","volume":"14","author":"Barratt","year":"2022","journal-title":"Sci Transl Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"S84","DOI":"10.1016\/S0163-4453(17)30196-2","article-title":"The respiratory microbiome and respiratory infections","volume":"74","author":"Unger","year":"2017","journal-title":"J Inf Secur"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s10096-018-03454-2","article-title":"Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED treatment)","volume":"38","author":"van","year":"2019","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s12519-019-00248-0","article-title":"Alterations of intestinal flora and the effects of probiotics in children with recurrent respiratory tract infection","volume":"15","author":"Li","year":"2019","journal-title":"World J Pediatr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1517\/14712598.2015.980233","article-title":"Probiotics for the prevention of pediatric upper respiratory tract infections: a systematic review","volume":"15","author":"Ozen","year":"2015","journal-title":"Expert Opin Biol Ther"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3920\/BM2017.0178","article-title":"Lactobacillus plantarum IS-10506 supplementation increases faecal sIgA and immune response in children younger than two years","volume":"10","author":"Kusumo","year":"2019","journal-title":"Benefic Microbes"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.chom.2014.03.006","article-title":"Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms","volume":"15","author":"Dasgupta","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.jff.2013.12.015","article-title":"Characterisation of bifidobacteria with immunomodulatory properties isolated from human breast milk","volume":"7","author":"Chiu","year":"2014","journal-title":"J Funct Foods"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fnut.2023.1319873","article-title":"Safety, efficacy, and impact on gut microbial ecology of a Bifidobacterium longum subspecies infantis LMG11588 supplementation in healthy term infants: a randomized, double-blind, controlled trial in the Philippines","volume":"10","author":"Capeding","year":"2023","journal-title":"Front Nutr"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12887-017-0886-9","article-title":"Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: a phase I clinical trial","volume":"17","author":"Smilowitz","year":"2017","journal-title":"BMC Pediatr"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1542\/peds.2004-1815","article-title":"Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents","volume":"115","author":"Weizman","year":"2005","journal-title":"Pediatrics"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.21315\/eimj2017.9.4.3","article-title":"Development, translation and validation of questionnaires for diarrhea and respiratory-related illnesses during probiotic administration in children","volume":"9","author":"Lau","year":"2017","journal-title":"Educ Med J"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006895.pub4","article-title":"Probiotics for preventing acute upper respiratory tract infections","author":"Zhao","year":"2022","journal-title":"Cochrane Database Syst Rev"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e4509","DOI":"10.1097\/MD.0000000000004509","article-title":"Probiotics for prevention and treatment of respiratory tract infections in children: a systematic review and meta-analysis of randomized controlled trials","volume":"95","author":"Wang","year":"2016","journal-title":"Medicine"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fimmu.2021.741233","article-title":"Gut\u2013lung Axis: microbial crosstalk in pediatric respiratory tract infections","volume":"12","author":"Zhu","year":"2021","journal-title":"Front Immunol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nrmicro.2016.142","article-title":"Emerging pathogenic links between microbiota and the gut\u2013lung axis","volume":"15","author":"Budden","year":"2016","journal-title":"Nat Rev Microbiol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/1471-2334-14-194","article-title":"Do children's upper respiratory tract infections benefit from probiotics?","volume":"14","author":"Esposito","year":"2014","journal-title":"BMC Infect Dis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1177\/1753465810379010","article-title":"Efficacy of a synbiotic supplementation in the prevention of common winter diseases in children: a randomized, double-blind, placebo-controlled pilot study","volume":"4","author":"Cazzola","year":"2010","journal-title":"Ther Adv Respir Dis"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e0210064","DOI":"10.1371\/journal.pone.0210064","article-title":"Pilot study of probiotic\/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms","volume":"14","author":"Sanctuary","year":"2019","journal-title":"PLoS One"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41390-019-0533-2","article-title":"Colonization by B. infantis EVC001 modulates enteric inflammation in exclusively breastfed infants","volume":"86","author":"Henrick","year":"2019","journal-title":"Pediatr Res"},{"key":"ref25","volume-title":"Bacteriostatic abilities of viable and heat-killed lactic acid bacteria against group B streptococcus","author":"Shan","year":"2011"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e920583","DOI":"10.12659\/MSM.920583","article-title":"Bifidobacterium infantis relieves allergic asthma in mice by regulating Th1\/Th2","volume":"26","author":"Wang","year":"2020","journal-title":"Med Sci Monit"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3884","DOI":"10.1016\/j.cell.2021.05.030","article-title":"Bifidobacteria-mediated immune system imprinting early in life","volume":"184","author":"Henrick","year":"2021","journal-title":"Cell"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"974066","DOI":"10.3389\/fimmu.2022.974066","article-title":"Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma","volume":"13","author":"Luo","year":"2022","journal-title":"Front Immunol"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1537610\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:13:39Z","timestamp":1739942019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1537610\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":28,"alternative-id":["10.3389\/fnut.2025.1537610"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1537610","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"article-number":"1537610"}}