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Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome.

  • 2017-11
  • The American Journal of Clinical Nutrition 106(5)
    • Monika Bazanella
    • T. V. Maier
    • T. Clavel
    • I. Lagkouvardos
    • M. Lucio
    • María X. Maldonado-Gomez
    • C. Autran
    • J. Walter
    • L. Bode
    • P. Schmitt‐Kopplin
    • D. Haller

Abstract

Background: Early-life colonization of the intestinal tract is a dynamic process influenced by numerous factors. The impact of probiotic-supplemented infant formula on the composition and function of the infant gut microbiota is not well defined.Objective: We sought to determine the effects of a bifidobacteria-containing formula on the healthy human intestinal microbiome during the first year of life.Design: A double-blind, randomized, placebo-controlled study of newborn infants assigned to a standard whey-based formula containing a total of 107 colony-forming units (CFU)/g of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, B. longum subspecies infantis (intervention), or to a control formula without bifidobacteria (placebo). Breastfed controls were included. Diversity and composition of fecal microbiota were determined by 16S ribosomal RNA gene amplicon sequencing, and metabolite profiles were analyzed by ultrahigh-performance liquid chromatography-mass spectrometry over a period of 2 y.Results: Infants (n = 106) were randomly assigned to either the interventional (n = 48) or placebo (n = 49) group; 9 infants were exclusively breastfed throughout the entire intervention period of 12 mo. Infants exposed to bifidobacteria-supplemented formula showed decreased occurrence of Bacteroides and Blautia spp. associated with changes in lipids and unknown metabolites at month 1. Microbiota and metabolite profiles of intervention and placebo groups converged during the study period, and long-term colonization (24 mo) of the supplemented Bifidobacterium strains was not detected. Significant differences in microbiota and metabolites were detected between infants fed breast milk and those fed formula (P < 0.005) and between infants birthed vaginally and those birthed by cesarean delivery (P < 0.005). No significant differences were observed between infant feeding groups regarding growth, antibiotic uptake, or other health variables (P > 0.05).Conclusion: The supplementation of bifidobacteria to infant diet can modulate the occurrence of specific bacteria and metabolites during early life with no detectable long-term effects. This trial was registered at germanctr.de as DRKS00003660.

Keywords: 16S rRNA gene; bifidobacteria; breastfeeding; infant gut microbiota; metabolomics; probiotics.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Bifidobacterium bifidum SD-6576Improved General HealthNeutral
Small
Bifidobacterium bifidum SD-6576Improved Gut Microbiota CompositionNeutral
Small
Bifidobacterium bifidum SD-6576Modulated Metabolite ProfileNeutral
Small
Bifidobacterium bifidum UABb-10Lack of Long-Term Colonization of Bifidobacteria StrainsNeutral
Small
Bifidobacterium bifidum UABb-10No Significant Change in Health VariablesNeutral
Small
Bifidobacterium breve BBr60No Significant Differences in GrowthNeutral
Small
Bifidobacterium breve Rosell-70Altered Gut Microbiota CompositionBeneficial
Moderate
Bifidobacterium breve Rosell-70Enhanced Long-Term Colonization of Supplemented BacteriaNeutral
Small
Bifidobacterium breve Rosell-70Modulated Metabolite ProfileNeutral
Small
Bifidobacterium longum Rosell-175No Long-Term Impact on Gut MicrobiotaNeutral
Small
Bifidobacterium longum Rosell-175No Significant Change in Health VariablesNeutral
Small
Bifidobacterium longum subsp. infantis M-63Improved Gut Microbiota CompositionNeutral
Small
Bifidobacterium longum subsp. infantis M-63Lack of Long-Term Colonization of Bifidobacteria StrainsNeutral
Small
Bifidobacterium longum subsp. infantis M-63No Influence on Infant GrowthNeutral
Small
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