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.

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.

Fig 1

Trial flow of patients.

Fig 2

Median (range) rhinovirus load (log₁₀ copies per sample) obtained when respiratory symptoms were present on days 1, 5, 10, and 15 of the episodes and in asymptomatic infants in the 3 study groups. No significant differences were detected among the study groups at any time point (P = .650 on day 1, P = .605 on day 5, P = .856 on day 10, P = .121 on day 15, and P = .990 in asymptomatic infants). The difference between symptomatic infants on day 1 and asymptomatic infants was significant (P < .001).

Fig 3

Rhinovirus load (log₁₀ copies per sample) obtained in the 5 infants with asymptomatic rhinovirus-positive findings. Rhinovirus quantitative RT-PCR was performed on days 5, 10, and 15 after a verified asymptomatic rhinovirus RNA finding (day 1) to determine the duration of viral shedding.