Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics.

Rebbeca M Duar,Steven A Frese,Lindsey N.C Scofield,Camila A Ortega Ramirez,Bethany M Henrick,Giorgio Casaburi,Daniela Barile,Ryan D Mitchell

doi:10.3390/nu12113247

Abstract

Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic differences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants.

Highlights

Hospitalization, surgical birth, antibiotic exposure, and many routine perinatal interventions are known to have detrimental effects on the gut microbiome, resulting in dysbiosis [1]
In order to determine the genomic characteristics of distinct B. infantis strains, we sequenced and closed the genomes of 12 isolates obtained from probiotic products targeted for pediatric populations (Table 1)
Based on results presented here, we predict that strain-specific differences in the functional ability of B. infantis probiotics will manifest in the colonization of the infant gut

Summary

Introduction

Hospitalization, surgical birth, antibiotic exposure, and many routine perinatal interventions are known to have detrimental effects on the gut microbiome, resulting in dysbiosis [1]. The negative effects of dysbiosis can be acute and/or long lasting [2,3]. Dysbiosis is linked to the pathogenesis of common neonatal conditions including necrotizing enterocolitis (NEC) and sepsis [4]. Human milk has been linked to improved infant outcomes with respect to acute and long-term disease risk. These benefits are in part provided by favoring the growth of specific beneficial bifidobacteria capable of consuming human milk oligosaccharides (HMOs) [5].

Objectives

Methods

Results

Discussion

Conclusion