The preterm gut microbiota and administration routes of different probiotics: a randomized controlled trial.

Ella-Noora Rahkola, Samuli Rautava, Henni Hiltunen, Chandler Ross, Leo Lahti, Erika Isolauri

Journal: Pediatric research 2023;94(4):1480-1487

PMID: 37020105

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The gut microbiota of healthy term vaginally delivered breast-fed children is rich in bifidobacteria. Preterm children, in turn, have aberrant gut microbiota which accommodate high abundances of facultative anaerobic bacteria, especially Enterobacteriaceae and Enterococcaceae. The aim of this study was to investigate the gut microbiota of preterm children and their susceptibility to infections and inflammation. This study randomised, double-blind, placebo-controlled clinical trial recruited preterm neonates and their mothers. The mothers with their newborn/s were randomly assigned into one of the five intervention groups. The gut microbiota compositions of the study subjects (68 children) were assessed using faecal samples obtained 7 days after birth. Results showed that the unmodulated microbiota of the preterm children is typified by facultative anaerobic and possibly pathogenic species such as Staphylococcus saprophyticus while bifidobacteria tend to be absent. Additionally, there were no adverse effects in preterm neonates who were directly administered living bacteria. Authors concluded that by administering preterm children directly the probiotic combination (containing Lactobacillus and Bifidobacterium strains) once a day, beginning from the first enteral feed, it is possible to increase the number of bifidobacteria in these children’s gut microbiota by 7 days of age.

Abstract

BACKGROUND

Preterm children with their aberrant gut microbiota and susceptibility to infections and inflammation constitute a considerable target group for probiotic therapy to generate the age-appropriate healthy microbiota.

METHODS

68 preterm neonates were randomized into five intervention groups: Beginning from the median age of 3 days, 13 children received Lactobacillus rhamnosus GG (LGG) directly orally, and 17 via the lactating mother. 14 children received LGG with Bifidobacterium lactis Bb-12 (Bb12) orally, and 10 via the lactating mother. 14 children received placebo. The children's faecal microbiota was assessed at the age of 7 days by 16S rRNA gene sequencing.

RESULTS

The gut microbiota compositions of the children directly receiving the probiotic combination (LGG + Bb12) were significantly different from those of the children receiving the other intervention modes or placebo (p = 0.0012; PERMANOVA), the distinction being due to an increase in the relative abundance of Bifidobacterium animalis (P < 0.00010; ANCOM-BC), and the order Lactobacillales (P = 0.020; ANCOM-BC).

CONCLUSION

The connection between aberrant primary gut microbiota and a heightened risk of infectious and non-communicable diseases invites effective microbiota modulation. We show that the direct, early, and brief probiotic intervention of LGG + Bb12 10 CFU each, is sufficient to modulate the gut microbiota of the preterm neonate.

IMPACT

Preterm children have a higher risk of several health problems partly due to their aberrant gut microbiota. More research is needed to find a safe probiotic intervention to modify the gut microbiota of preterm children. The maternal administration route via breast milk might be safer for the newborn. In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not as effective.

© 2023. The Author(s).

Address: Department of Clinical Sciences, Faculty of Medicine, University of Turku, Turku, Finland. [email protected].; Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland. [email protected].; Department of Clinical Sciences, Faculty of Medicine, University of Turku, Turku, Finland.; Department of Pediatrics, University of Helsinki and Children's Hospital, Helsinki University Hospital, Helsinki, Finland.; Department of Clinical Sciences, Faculty of Medicine, University of Turku, Turku, Finland.; Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.; Department of Computing, University of Turku, Turku, Finland.

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