Delayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation

Juliana Durack,Ariane R Panzer,Din L Lin,Marcus Rauch,Michael D Cabana,Susan V Lynch,Kathryn Mccauley,Jordan S Mar,Michelle Mckean,Nikole E Kimes

doi:10.1038/s41467-018-03157-4

Abstract

Gut microbiota dysbiosis and metabolic dysfunction in infancy precedes childhood atopy and asthma development. Here we examined gut microbiota maturation over the first year of life in infants at high risk for asthma (HR), and whether it is modifiable by early-life Lactobacillus supplementation. We performed a longitudinal comparison of stool samples collected from HR infants randomized to daily oral Lactobacillus rhamnosus GG (HRLGG) or placebo (HRP) for 6 months, and healthy (HC) infants. Meconium microbiota of HRP participants is distinct, follows a delayed developmental trajectory, and is primarily glycolytic and depleted of a range of anti-inflammatory lipids at 6 months of age. These deficits are partly rescued in HRLGG infants, but this effect was lost at 12 months of age, 6 months after cessation of supplementation. Thus we show that early-life gut microbial development is distinct, but plastic, in HR infants. Our findings offer a novel strategy for early-life preventative interventions.

Highlights

Gut microbiota dysbiosis and metabolic dysfunction in infancy precedes childhood atopy and asthma development
We took advantage of a randomly chosen subset of infants enrolled in the double-blind, placebo controlled trial of infant probiotic supplementation (TIPS) study[10]; designed to examine the effects of early-life Lactobacillus rhamnosus GG (LGG) supplementation on childhood allergy and asthma development, in a high risk for asthma (HR) population (HR; n = 25)
Adherence to supplementation over the 6-month period was assessed by both quantitative PCR and sequence-based abundance of LGG which confirmed a significantly higher relative abundance of Lactobacillus in high-risk LGG-supplemented (HRLGG) compared to placebo (HRP) treated infants during the active supplementation period (Supplementary Figure 2a and b)

Summary

Introduction

Gut microbiota dysbiosis and metabolic dysfunction in infancy precedes childhood atopy and asthma development. Founder species, those to first colonize a previously pristine environment, frequently dictate biome conditions and influence both the pace and subsequent pattern of species accumulation in the developing ecosystem[9] Using this theoretical framework, we hypothesized that neonates at high risk for asthma (HR) exhibit meconium gut microbiota dysbiosis and a reduced rate of gut bacterial diversification over the first year of life. We show that children at HR for asthma, exhibit a distinct pioneer meconium microbiota, delayed gut microbial diversification and are depleted for a range of anti-inflammatory fecal lipids in infancy These deficits are partly rescued following LGG supplementation, and the products of LGG-supplemented infant gut microbiomes at 6 months of age, were found to increase the number of regulatory T cells ex vivo. They indicate nascent gut microbiome manipulation offers a feasible approach for immunomodulation in humans, and offer a much-needed framework for therapeutic development and future studies

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Conclusion