{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:50:55Z","timestamp":1790196655084,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mead &amp; Johnson Nutrition","award":["NCT02116452"],"award-info":[{"award-number":["NCT02116452"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Early nutrition affects the risk of atopy and infections through modifications of intestinal microbiota. The Prebiotics in the Prevention of Atopy (PIPA) study was a 24-month randomised, double-blind, placebo-controlled trial. It aimed to evaluate the effects of a galacto-oligosaccharide\/polydextrose (GOS\/PDX)-formula (PF) on atopic dermatitis (AD) and common infections in infants who were born to atopic parents and to investigate the relationship among early nutrition, gut microbiota and clinical outcomes. Methods: A total of 201 and 199 infants were randomized to receive a PF and standard formula (SF), respectively; 140 infants remained on exclusive breastfeeding (BF). Results: The cumulative incidence of AD and its intensity and duration were not statistically different among the three groups. The number of infants with at least one episode of respiratory infection (RI) and the mean number of episodes until 48 weeks of age were significantly lower in the PF group than in the SF group. The number of patients with recurrent RIs and incidence of wheezing lower RIs until 96 weeks were lower in the PF group than the SF group, but similar to the BF group. Bifidobacteria and Clostridium cluster I colonization increased over time in the PF group but decreased in the SF and BF groups. Bifidobacteria had a protective role in RIs, whereas Clostridium cluster I was associated with atopy protection. Conclusion: The early administration of PF protects against RIs and mediates a species-specific modulation of the intestinal microbiota. Trial registration: clinicaltrial.gov Identifier: NCT02116452.<\/jats:p>","DOI":"10.3390\/nu10030286","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T12:15:44Z","timestamp":1519906544000},"page":"286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Galacto-Oligosaccharide\/Polidextrose Enriched Formula Protects against Respiratory Infections in Infants at High Risk of Atopy: A Randomized Clinical Trial"],"prefix":"10.3390","volume":"10","author":[{"given":"Giusy","family":"Ranucci","sequence":"first","affiliation":[{"name":"Unit of Pediatrics, Department of Translational Medical Science, University Federico II, Via Pansini 5, 80131 Naples, Italy"},{"name":"Bambino Ges\u00f9 Children\u2019s Hospital, Division of Metabolism, Piazza di Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-4124","authenticated-orcid":false,"given":"Vittoria","family":"Buccigrossi","sequence":"additional","affiliation":[{"name":"Unit of Pediatrics, Department of Translational Medical Science, University Federico II, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Borgia","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padua, Via Giustiniani 3, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Piacentini","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padua, Via Giustiniani 3, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Visentin","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padua, Via Giustiniani 3, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Cantarutti","sequence":"additional","affiliation":[{"name":"Pedianet Network, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Baiardi","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri SpA Benefit Corporation, Via S. Severino Boezio, 28, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7315-0857","authenticated-orcid":false,"given":"Mariagrazia","family":"Felisi","sequence":"additional","affiliation":[{"name":"Consorzio per Valutazioni Biologiche e Farmacologiche, Via Luigi Porta, 14, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Spagnuolo","sequence":"additional","affiliation":[{"name":"Unit of Pediatrics, Department of Translational Medical Science, University Federico II, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Zanconato","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padua, Via Giustiniani 3, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Baraldi","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padua, Via Giustiniani 3, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Giaquinto","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, University of Padua, Via Giustiniani 3, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Guarino","sequence":"additional","affiliation":[{"name":"Unit of Pediatrics, Department of Translational Medical Science, University Federico II, Via Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Austin, S., De Castro, C.A., B\u00e9net, T., Hou, Y., Sun, H., Thakkar, S.K., Vinyes-Pares, G., Zhang, Y., and Wang, P. (2016). Temporal change of the content of 10 oligosaccharides in the milk of Chinese urban mothers. Nutrients, 8.","DOI":"10.3390\/nu8060346"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3945\/jn.116.238279","article-title":"Absolute quantitation of human milk oligosaccharides reveals phenotypic variations during lactation","volume":"147","author":"Xu","year":"2017","journal-title":"J. Nutr."},{"key":"ref_3","first-page":"61","article-title":"Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods","volume":"30","author":"Harmsen","year":"2000","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1017\/S0007114510003363","article-title":"Prebiotic effects: Metabolic and health benefits","volume":"104","author":"Roberfroid","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1440-1754.2007.01033.x","article-title":"Occurrence and management of acute respiratory illnesses in early childhood","volume":"43","author":"Kusel","year":"2007","journal-title":"J. Paediatr. Child Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/MPG.0b013e3181fb9e80","article-title":"ESPGHAN Committee on Nutrition. Supplementation of infant formula with probiotics and\/or prebiotics: A systematic review and comment by the ESPGHAN committee on nutrition","volume":"52","author":"Braegger","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Osborn, D.A., and Sinn, J.K. (2013). Prebiotics in infants for prevention of allergy. Cochrane Database Syst. Rev., 3.","DOI":"10.1002\/14651858.CD006474.pub3"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.clnu.2009.01.008","article-title":"A formula containing galacto- and fructo-oligosaccharides prevents intestinal and extra-intestinal infections: an observational study","volume":"28","author":"Bruzzese","year":"2009","journal-title":"Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1093\/jn\/137.11.2420","article-title":"Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life","volume":"137","author":"Arslanoglu","year":"2007","journal-title":"J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/jn\/138.6.1091","article-title":"Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life","volume":"138","author":"Arslanoglu","year":"2008","journal-title":"J. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.jaci.2010.07.022","article-title":"MIPS 1 Working Group. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants","volume":"126","author":"Mosca","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/j.jaci.2015.07.049","article-title":"MIPS II Working Group. Immunoactive prebiotics transiently prevent occurrence of early atopic dermatitis among low-atopy-risk infants","volume":"136","author":"Mosca","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00394-014-0689-9","article-title":"Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: A multicentre, randomised, double-blind and placebo-controlled trial","volume":"54","author":"Sierra","year":"2015","journal-title":"Eur. J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.3945\/jn.111.143727","article-title":"Polydextrose enrichment of infant formula demonstrates prebiotic characteristics by altering intestinal microbiota, organic acid concentrations, and cytokine expression in suckling piglets","volume":"141","author":"Herfel","year":"2011","journal-title":"J. Nutr."},{"key":"ref_15","unstructured":"Food and Drug Administration (FDA) (2007). GRAS Notification."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1111\/j.1399-3038.2005.00333.x","article-title":"Etiology of atopy in infancy: The KOALA Birth Cohort Study","volume":"16","author":"Kummeling","year":"2005","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1034\/j.1398-9995.2000.00117.x","article-title":"The lessons of noninterventional and interventional prospective studies on the development of atopic disease during childhood","volume":"55","author":"Halken","year":"2000","journal-title":"Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/j.1399-3038.2004.00128.x","article-title":"Dietary prevention of allergic diseases in infants and small children. Part II: evaluation of methods in allergy prevention studies and sensitization markers. Definitions and diagnostic criteria for allergic diseases","volume":"15","author":"Muraro","year":"2004","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1159\/000356451","article-title":"Definitions and outcomes of nutritional interventions in children with respiratory infections: the approach of the COMMENT initiative","volume":"63","author":"Guarino","year":"2013","journal-title":"Ann. Nutr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1111\/j.1398-9995.2007.01462.x","article-title":"The role of the intestinal microbiota in the development of atopic disorders","volume":"62","author":"Penders","year":"2007","journal-title":"Allergy"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bruzzese, E., Callegari, M.L., Raia, V., Viscovo, S., Scotto, R., Ferrari, S., Morelli, L., Buccigrossi, V., Lo Vecchio, A., and Ruberto, E. (2014). Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: A randomised clinical trial. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087796"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1097\/INF.0b013e3182620e52","article-title":"The role of prebiotics and probiotics in prevention and treatment of childhood infectious diseases","volume":"31","author":"Weichert","year":"2012","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1183\/09031936.00193310","article-title":"Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze","volume":"39","author":"Kusel","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1111\/resp.12371","article-title":"They said it was bronchiolitis: Is it going to turn into asthma doctor?","volume":"19","author":"Gidaris","year":"2014","journal-title":"Respirology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1067\/mai.2001.111237","article-title":"Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing","volume":"107","author":"Kalliomaki","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000092555","article-title":"Distinct pattern of commensal gut microbiota in toddlers with eczema","volume":"140","author":"Mah","year":"2006","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/j.1574-695X.2011.00872.x","article-title":"Aberrant structures of fecal bacterial community in allergic infants profiled by 16S rRNA gene pyrosequencing","volume":"63","author":"Nakayama","year":"2011","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.jaci.2013.05.043","article-title":"Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood","volume":"132","author":"Penders","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s00535-015-1084-x","article-title":"A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and anti-inflammatory response in inflammatory bowel disease","volume":"50","author":"Kanai","year":"2015","journal-title":"J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liao, H.Y., Tao, L., Zhao, J., Qin, J., Zeng, G.C., Cai, S.W., Li, Y., Zhang, J., and Chen, H.G. (2016). Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients. Sci. Rep., 6.","DOI":"10.1038\/srep20481"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bin, L., Yang, F., Lu, D., and Lin, Z. (2016). Specific immunotherapy plus Clostridium butyricum alleviates ulcerative colitis in patients with food allergy. Sci. Rep., 6.","DOI":"10.1038\/srep25587"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.micpath.2016.09.008","article-title":"Effects of clostridium butyricum and bifidobacterium on BTLA expression on CD4+ T cells and lymphocyte differentiation in late preterm infants","volume":"100","author":"Zhang","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/adc.2006.098251","article-title":"A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age","volume":"91","author":"Moro","year":"2006","journal-title":"Arch. Dis. Child."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/3\/286\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:04Z","timestamp":1760194624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/3\/286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,1]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["nu10030286"],"URL":"https:\/\/doi.org\/10.3390\/nu10030286","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,1]]}}}