title: Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial.
abstract: BACKGROUND
  Simple and safe strategies for the prevention of viral respiratory tract infections (RTIs) are needed.
  
  
  OBJECTIVE
  We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov no. NCT00167700), 94 preterm infants (gestational age, ≥32 + 0 and ≤36 + 6 weeks; birth weight, >1500 g) treated at Turku University Hospital, Turku, Finland, were allocated to receive oral prebiotics (galacto-oligosaccharide and polydextrose mixture, 1:1), a probiotic (Lactobacillus rhamnosus GG, ATCC 53103), or placebo (microcrystalline cellulose) between days 3 and 60 of life. The primary outcome was the incidence of clinically defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing. Secondary outcomes were the severity and duration of RTIs.
  
  
  RESULTS
  A significantly lower incidence of RTIs was detected in infants receiving prebiotics (rate ratio [RR], 0.24; 95% CI, 0.12-0.49; P < .001) or probiotics (RR, 0.50; 95% CI, 0.28-0.90; P = .022) compared with those receiving placebo. Also, the incidence of rhinovirus-induced episodes, which comprised 80% of all RTI episodes, was found to be significantly lower in the prebiotic (RR, 0.31; 95% CI, 0.14-0.66; P = .003) and probiotic (RR, 0.49; 95% CI, 0.24-1.00; P = .051) groups compared with the placebo group. No differences emerged among the study groups in rhinovirus RNA load during infections, duration of rhinovirus RNA shedding, duration or severity of rhinovirus infections, or occurrence of rhinovirus RNA in asymptomatic infants.
  
  
  CONCLUSIONS
  Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland. Electronic address: raakel.luoto@utu.fi.
authors.forename: Raakel
authors.initials: R
authors.lastname: Luoto
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ruuskanen
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Waris
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Kalliomäki
authors.affiliation: Functional Foods Forum, University of Turku, Turku, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Salminen
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Isolauri
mesh_terms: D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D010850:Picornaviridae Infections / Q000517:prevention & control* / Q000821:virology; D056692:Prebiotics; D019936:Probiotics / Q000627:therapeutic use*; D012140:Respiratory Tract Diseases / Q000517:prevention & control* / Q000821:virology; D012229:Rhinovirus / Q000502:physiology*; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D056692:Prebiotics
keywords: Galacto-oligosaccharide; Lactobacillus rhamnosus GG; RR; RSV; RTI; Rate ratio; Respiratory syncytial virus; Respiratory tract infection; gut microbiota; polydextrose; prebiotic; preterm infant; probiotic; respiratory tract infections; rhinovirus