The impact of early-life Lactobacillus rhamnosus GG supplementation on the composition of the bacterial gut microbiota was assessed in high-risk for asthma infants.

Rationale: Early-life gastrointestinal microbiome perturbation is associated with immune activation and childhood allergic asthma development. The impact of early-life Lactobacillus rhamnosus GG (LGG) supplementation on the composition and functional development of the gut microbiome was assessed using a multi-omics approach in high-risk (HR) for asthma infants. Methods: Stool samples from 29 healthy (HC) and 25 HR infants (enrolled in a double-blind, randomized, placebo control trial of daily supplementation with 1x1010 LGG from birth to 6mo) were collected at birth, 1, 3, 6, 9 and 12mo of age, and subjected to parallel 16S rRNA-based microbiome profiling using Illumina MiSeq and un-targeted liquid chromatography mass spectrometry metabolic analysis. An ex vivo dendritic cell challenge and T cell co-culture was used to investigate the effect of sterile fecal water from a subset of 6mo and 12mo samples on immune activation.Results: LGG supplementation partially rescued the delayed rate of Faith's phylogenetic diversity gain in the first year of life of HR infants, shifting the bacterial (1mo-12mo) and metabolic composition (6mo) to resemble that of HC infants. LGG promoted expansion of a small (18% of all healthy OTUs) but consistent group of protective bacterial species (1mo-12mo) and a small portion of metabolites (26% of all healthy metabolites) including an array anti-inflammatory lipids (6mo). LGG-supplemented metabolic milieu promoted CD4+CD25+Foxp3+ (T-regulatory) cell expansion and IL10 production. However, this protective metabolic signature was not sustained after cessation of supplementation at 12mo of age. Conclusions: Continuous early-life supplementation with LGG partially reprograms gut microenvironment associated with immune tolerance in HR infants. Extended and expanded supplementation with supporting groups of bacteria depleted in HR infants may be necessary for sustained and sufficient metabolic reprograming of the gut microenvironment to achieve the desired clinical outcomes.