{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:23:33Z","timestamp":1788805413775,"version":"build-2803163510"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p>To describe microbiota profiles considering potential influencing factors in pre-school children with recurrent respiratory tract infections (rRTIs) and to evaluate microbiota changes associated with oral bacterial lysate OM-85 treatment, we analyzed gut and nasopharynx (NP) microbiota composition in patients included in the OM-85-pediatric rRTIs (OMPeR) clinical trial (<jats:uri>https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/trial\/2016-002705-19\/IT<\/jats:uri>). Relative percentage abundance was used to describe microbiota profiles in all the available biological specimens, grouped by age, atopy, and rRTIs both at inclusion (T0) and at the end of the study, after treatment with OM-85 or placebo (T1). At T0, <jats:italic>Firmicutes<\/jats:italic> and <jats:italic>Bacteriodetes<\/jats:italic> were the predominant genera in gut and <jats:italic>Proteobacteria<\/jats:italic>, <jats:italic>Firmicutes<\/jats:italic>, and <jats:italic>Actinobacteria<\/jats:italic> were the predominant genera in NP samples. Gut microbiota relative composition differed with age (&amp;lt;2 vs. \u22652 years) for <jats:italic>Firmicutes, Proteobacteria, Actinobacteria<\/jats:italic> (phyla) and <jats:italic>Bifidobacterium, Ruminococcus, Lachnospiraceae<\/jats:italic> (genera) (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). <jats:italic>Moraxella<\/jats:italic> was more enriched in the NP of patients with a history of up to three RTIs. Intra-group changes in relative percentage abundance were described only for patients with gut and NP microbiota analysis available at both T0 and T1 for each study arm. In this preliminary analysis, the gut microbiota seemed more stable over the 6-month study in the OM-85 group, whose mean age was lower, as compared to the placebo group (<jats:italic>p<\/jats:italic> = 0.004). In this latter group, the relative abundance of <jats:italic>Bacteroides<\/jats:italic> decreased significantly in children \u22652 years. Some longitudinal significant differences in genera relative abundance were also detected in children of \u22652 years for NP <jats:italic>Actinobacteria<\/jats:italic>, <jats:italic>Haemophilus<\/jats:italic>, and <jats:italic>Corynebacterium<\/jats:italic> in the placebo group only. Due to the small number of patients in the different sub-populations, we could not identify significant differences in the clinical outcome and therefore no associations with microbiota changes were searched. The use of bacterial lysates might play a role in microbiota rearrangement, but further data and advanced analysis are needed to prove this in less heterogeneous populations with higher numbers of samples considering the multiple influencing factors such as delivery method, age, environment, diet, antibiotic use, and type of infections to ultimately show any associations with prevention of rRTIs.<\/jats:p>","DOI":"10.3389\/fcimb.2022.789436","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T10:24:40Z","timestamp":1660645480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Microbiota profiles in pre-school children with respiratory infections: Modifications induced by the oral bacterial lysate OM-85"],"prefix":"10.3389","volume":"12","author":[{"given":"Susanna","family":"Esposito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Ballarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Argentiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Ruggiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni A.","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Principi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/nature09944","article-title":"Enterotypes of the human gut microbiome","volume":"473","author":"Arumugam","year":"2011","journal-title":"Nature."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1164\/rccm.201407-1240OC","article-title":"Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children","volume":"190","author":"Biesbroek","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.zool.2011.04.001","article-title":"Metaorganisms as the new frontier","volume":"114","author":"Bosch","year":"2011","journal-title":"Zool (Jena)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high\u2013throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"B5","doi-asserted-by":"publisher","first-page":"43844","DOI":"10.1038\/srep43844","article-title":"OM\u201385 is an immunomodulator of interferon\u2013\u03b2 production and inflammasome activity","volume":"7","author":"Dang","year":"2017","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1016\/j.jaci.2016.05.050","article-title":"Bacterial microbiota of the upper respiratory tract and childhood asthma","volume":"139","author":"Depner","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"E280","DOI":"10.1371\/journal.pbio.0060280","article-title":"The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing","volume":"6","author":"Dethlefsen","year":"2008","journal-title":"PloS Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/s12967-019-2040-y","article-title":"A randomized, placebo\u2013controlled, double\u2013blinded, single\u2013centre, phase IV trial to assess the efficacy and safety of OM\u201385 in children suffering from recurrent respiratory tract infections","volume":"17","author":"Esposito","year":"2019","journal-title":"J. Transl. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1097\/ACI.0000000000000433","article-title":"Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence","volume":"18","author":"Esposito","year":"2018","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.pharmthera.2013.08.002","article-title":"Microbiota abnormalities in inflammatory airway diseases \u2013 potential for therapy","volume":"141","author":"Gollwitzer","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1016\/j.jaci.2018.08.035","article-title":"Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development","volume":"143","author":"Holt","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"B12","first-page":"209","article-title":"Th1\u2013orientated immunological properties of the bacterial extract OM\u201385\u2013BV","volume":"10","author":"Huber","year":"2005","journal-title":"Eur. J. Med. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00281-019-00775-y","article-title":"Dysbiosis of the gut and lung microbiome has a role in asthma","volume":"42","author":"Hufnagl","year":"2020","journal-title":"Springer Semin. Immunopathol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1164\/rccm.200806-951OC","article-title":"Lactobacillus reuteri\u2013induced regulatory T cells protect against an allergic airway response in mice","volume":"179","author":"Karimi","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01830","article-title":"Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer","volume":"9","author":"Lazar","year":"2018","journal-title":"Front. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/nrmicro.2017.14","article-title":"The microbiota of the respiratory tract: gatekeeper to respiratory health","volume":"15","author":"Man","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/S2213-2600(19)30470-9","article-title":"Infant respiratory syncytial virus prophylaxis and nasopharyngeal microbiota until 6 years of life: a subanalysis of the MAKI randomised controlled trial","volume":"8","author":"Man","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1056\/NEJMcibr2011679","article-title":"Trained innate immunity, epigenetics, and covid\u201319","volume":"383","author":"Mantovani","year":"2020","journal-title":"N Engl. J. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S2213-2600(18)30449-1","article-title":"Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case\u2013control study","volume":"7","author":"Man","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.coi.2017.08.003","article-title":"Immune development and environment: lessons from Amish and Hutterite children","volume":"48","author":"Ober","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"17057","DOI":"10.1038\/nmicrobiol.2017.57","article-title":"Next\u2013generation probiotics: the spectrum from probiotics to live biotherapeutics","volume":"2","author":"O\u2019Toole","year":"2017","journal-title":"Nat. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3390\/vaccines5040040","article-title":"Impact of the respiratory microbiome on host responses to respiratory viral infection","volume":"5","author":"Pichon","year":"2017","journal-title":"Vaccines (Basel)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/microorganisms7010014","article-title":"What is the healthy gut microbiota composition? a changing ecosystem across age, environment, diet, and diseases","volume":"7","author":"Rinninella","year":"2019","journal-title":"Microorganisms."},{"key":"B25","doi-asserted-by":"publisher","first-page":"17","DOI":"10.17925\/ERPD.2019.5.1.17","article-title":"Immunomodulation therapy \u2013 clinical relevance of bacterial lysates OM\u201385","volume":"5","author":"Rossi","year":"2019","journal-title":"Eur. Respir. pulmonary dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13601-020-00322-1","article-title":"Viral infections and wheezing\u2013asthma inception in childhood: is there a role for immunomodulation by oral bacterial lysates","author":"Rossi","year":"2020","journal-title":"Clin. Transl. Allergy"},{"key":"B27","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jceh.2018.04.016","article-title":"Methods for studying gut microbiota: A primer for physicians","volume":"9","author":"Sarangi","year":"2019","journal-title":"J. Clin. Exp. Hepatol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-021-02519-x","article-title":"Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies","author":"Shi","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.chom.2015.03.008","article-title":"The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development","volume":"17","author":"Teo","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3256","DOI":"10.3390\/ijms19103256","article-title":"How to process sputum samples and extract bacterial DNA for microbiota analysis","volume":"19","author":"Terranova","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.2217\/fmb.15.87","article-title":"L. fecal microbiota analysis: an overview of sample collection methods and sequencing strategies","volume":"10","author":"Thomas","year":"2015","journal-title":"Future Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/microorganisms8040573","article-title":"The controversial role of human gut lachnospiraceae","volume":"8","author":"Vacca","year":"2020","journal-title":"Microorganisms."},{"key":"B33","doi-asserted-by":"publisher","first-page":"8:19","DOI":"10.1186\/1471-2466-8-19","article-title":"Early intestinal bacteroides fragilis colonisation and development of asthma","author":"Vael","year":"2008","journal-title":"BMC Pulm Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s12931-020-01443-8","article-title":"Nasal microbiota dominated by moraxella spp. is associated with respiratory health in the elderly population: a case control study","volume":"21","author":"van den Munckhof","year":"2020","journal-title":"Respir. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"5828959","DOI":"10.1155\/2016\/5828959","article-title":"Lower level of bacteroides in the gut microbiota is associated with inflammatory bowel disease: A meta\u2013analysis","volume":"2016","author":"Zhou","year":"2016","journal-title":"BioMed. Res. Int."},{"key":"B36","doi-asserted-by":"publisher","first-page":"E87162","DOI":"10.1371\/journal.pone.0087162","article-title":"Increased risk of wheeze and decreased lung function after respiratory syncytial virus infection","volume":"9","author":"Zomer\u2013Kooijker","year":"2014","journal-title":"PloS One"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.789436\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T10:24:45Z","timestamp":1660645485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.789436\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,16]]},"references-count":36,"alternative-id":["10.3389\/fcimb.2022.789436"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.789436","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,16]]},"article-number":"789436"}}