Abstract
IntroductionProbiotic supplementation of preterm infants may prevent serious morbidities associated with prematurity.AimTo investigate the impact of probiotic supplementation on the gut microbiota and determine factors associated with detection of probiotic species in the infant gut.Hypothesis/Gap StatementProbiotic supplementation increases the long-term colonization of probiotic species in the gut of preterm infants.MethodologyLongitudinal stool samples were collected from a cohort of very preterm infants participating in a blinded randomized controlled trial investigating the impact of probiotic supplementation (containing Bifidobacterium longum subsp. infantis BB-02, Bifidobacterium animalis subsp. lactis BB-12 and Streptococcus thermophilus TH-4) for prevention of late-onset sepsis. The presence of B. longum subsp. infantis , B. animalis subsp. lactis and S. thermophilus was determined for up to 23 months after supplementation ended using real-time PCR. Logistic regression was used to investigate the impact of probiotic supplementation on the presence of each species.ResultsDetection of B. longum subsp. infantis [odds ratio (OR): 53.1; 95 % confidence interval (CI): 35.6–79.1; P < 0.001], B. animalis subsp. lactis (OR: 89.1; 95 % CI: 59.0–134.5; P < 0.001) and S. thermophilus (OR: 5.66; 95 % CI: 4.35–7.37; P < 0.001) was increased during the supplementation period in infants receiving probiotic supplementation. Post-supplementation, probiotic-supplemented infants had increased detection of B. longum subsp. infantis (OR: 2.53; 95 % CI: 1.64–3.90; P < 0.001) and B. animalis subsp. lactis (OR: 1.59; 95 % CI: 1.05–2.41; P=0.030). Commencing probiotic supplementation before 5 days from birth was associated with increased detection of the probiotic species over the study period ( B. longum subsp. infantis, OR: 1.20; B. animalis subsp. lactis, OR: 1.28; S. thermophilus, OR: 1.45).ConclusionProbiotic supplementation with B. longum subsp. infantis BB-02, B. animalis subsp. lactis BB-12 and S. thermophilus TH-4 enhances the presence of probiotic species in the gut microbiota of very preterm infants during and after supplementation. Commencing probiotic supplementation shortly after birth may be important for improving the long-term colonization of probiotic species.
Highlights
Probiotic supplementation of preterm infants may prevent serious morbidities associated with prematurity
Probiotic supplementation with B. longum subsp. infantis BB-02, B. animalis subsp. lactis BB-12 and S. thermophilus TH-4 enhances the presence of probiotic species in the gut microbiota of very preterm infants during and after supplementation
The Cq value of the three probiotic species was lower in infants receiving probiotic compared to placebo infants [B. longum subsp. infantis median Cq value=22 (IQR: 19, 27) vs. 45 (IQR: 45, 45), coefficient=−16.63, 95 % confidence interval (CI): –17.68, –15.58; P < 0.001, B. animalis subsp. lactis median Cq value=32 (IQR: 28, 36) vs. 45 (IQR: 45, 45), coefficient=−11.70, 95 % CI: –12.29, –11.09; P < 0.001 and S. thermophilus median Cq value=45 (IQR: 40, 45) vs. 45 (IQR: 45, 45), coefficient=−1.41, 95 % CI: –1.92, –0.89; P < 0.001]
Summary
Probiotic supplementation of preterm infants may prevent serious morbidities associated with prematurity. Preterm infants have an altered gastrointestinal microbiota compared with term infants, including reduced species diversity, reduced numbers of Bifidobacterium species and Lactobacillus species, and higher numbers of potentially pathogenic Enterobacteriaceae and Clostridium difficile [1, 2] These differences probably result from reduced exposure to maternal microbiota, from immaturity of the intestinal immune response, and from the various medical interventions necessary in management within neonatal intensive care units [3]. Recent systematic reviews and meta-analyses have reported that probiotic supplementation is effective for the prevention of serious morbidities associated with prematurity, including mortality, late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) [5,6,7,8]. The ProPrems RCT found that while administration of the probiotic was not associated with reduction in LOS or mortality, it resulted in a 54 % reduced risk of NEC of Bell stage 2 or more [10]
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