Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2'-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial

J Nutr. 2016 Dec;146(12):2559-2566. doi: 10.3945/jn.116.236919. Epub 2016 Oct 26.

Abstract

Background: Evidence suggests that human milk oligosaccharides (HMOs) provide multiple benefits to infants, including prebiotic effects, gut maturation, antimicrobial activities, and immune modulation. Clinical intervention studies with HMOs are required to confirm these benefits in infants.

Objective: Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2'-fucosyllactose (2'-FL) on biomarkers of immune function in healthy term infants.

Methods: We performed a substudy nested within a randomized, double-blind, controlled growth and tolerance study in healthy singleton infants (birth weight ≥2490 g) who were enrolled by 5 d of life and exclusively formula-fed (n = 317) or breastfed (n = 107) from enrollment to 4 mo of age. Formula-fed infants were randomly assigned to receive 1 of 3 formulas, all containing 2.4 g total oligosaccharides/L [control: galacto-oligosaccharides (GOS) only; experimental formulas: GOS + 0.2 or 1.0 g 2'-FL/L], and compared with a breastfed reference group. For this substudy, blood samples were drawn from infants at 6 wk of age (n = 31-42/group). Peripheral blood mononuclear cells (PBMCs) were isolated for cellular phenotyping and stimulated ex vivo with phytohemagglutinin for proliferation and cell cycle progression or respiratory syncytial virus (RSV). Cytokine concentrations were measured in plasma and in ex vivo-stimulated culture supernatants.

Results: Breastfed infants and infants fed either of the experimental formulas with 2'-FL were not different but had 29-83% lower concentrations of plasma inflammatory cytokines than did infants fed the control formula [interleukin (IL) receptor antagonist (IL-1ra), IL-1α, IL-1β, IL-6, and tumor necrosis factor α (TNF-α)] (P ≤ 0.05). In ex vivo RSV-stimulated PBMC cultures, breastfed infants were not different than either of the groups fed formula with 2'-FL, but they had lower concentrations of TNF-α (31%) and interferon γ (IFN-γ 54%) (P ≤ 0.05) and tended to have lower IL-1ra (25%) and IL-6 (38%) (unadjusted P ≤ 0.05) and IL-1β (30%) (unadjusted P = 0.06) than did infants fed the control formula.

Conclusions: Our data indicate that infants fed formula supplemented with 2'-FL exhibit lower plasma and ex vivo inflammatory cytokine profiles, similar to those of a breastfed reference group. This trial was registered at clinicaltrials.gov as NCT01808105.

Keywords: 2'-fucosyllactose; breastfed infants; galacto-oligosaccharides; human milk oligosaccharides; infant formula; inflammatory cytokines.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Breast Feeding*
  • Cell Proliferation
  • Cytokines / blood*
  • Cytokines / metabolism
  • Double-Blind Method
  • Gene Expression Regulation
  • Humans
  • Infant
  • Infant Formula / chemistry*
  • Infant, Newborn
  • Inflammation / blood
  • Inflammation / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Respiratory Syncytial Viruses / isolation & purification
  • Trisaccharides / administration & dosage
  • Trisaccharides / chemistry
  • Trisaccharides / pharmacology*
  • Viral Load

Substances

  • Cytokines
  • Trisaccharides
  • 2'-fucosyllactose

Associated data

  • ClinicalTrials.gov/NCT01808105