Goehring Karen C, Marriage Barbara J, Oliver Jeffery S, Wilder Julie A, Barrett Edward G, Buck Rachael H
Research and Development and.
Regulatory Affairs, Abbott Nutrition, Columbus, OH; and.
J Nutr. 2016 Dec;146(12):2559-2566. doi: 10.3945/jn.116.236919. Epub 2016 Oct 26.
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.
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.
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.
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.
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.
有证据表明，人乳寡糖（HMOs）对婴儿有多种益处，包括益生元效应、肠道成熟、抗菌活性和免疫调节。需要进行HMOs的临床干预研究来证实这些对婴儿的益处。
我们的目的是研究添加HMO 2'-岩藻糖基乳糖（2'-FL）的配方奶对健康足月儿免疫功能生物标志物的影响。
我们在一项针对健康单胎婴儿（出生体重≥2490 g）的随机、双盲、对照生长和耐受性研究中进行了一项子研究，这些婴儿在出生后5天内入组，从入组到4月龄完全采用配方奶喂养（n = 317）或母乳喂养（n = 107）。配方奶喂养的婴儿被随机分配接受3种配方奶中的1种，所有配方奶总寡糖含量均为2.4 g/L[对照组：仅含低聚半乳糖（GOS）；试验配方奶：GOS + 0.2或1.0 g 2'-FL/L]，并与母乳喂养参考组进行比较。在这项子研究中，在婴儿6周龄时（每组n = 31 - 42）采集血样。分离外周血单个核细胞（PBMCs）进行细胞表型分析，并在体外用人血细胞凝集素刺激以进行增殖和细胞周期进程研究或用呼吸道合胞病毒（RSV）刺激。在血浆和体外刺激的培养上清液中测量细胞因子浓度。
母乳喂养的婴儿和喂养含2'-FL试验配方奶的婴儿无差异，但与喂养对照配方奶的婴儿相比，其血浆炎症细胞因子浓度低29% - 83%[白细胞介素（IL）受体拮抗剂（IL-1ra）、IL-1α、IL-1β、IL-6和肿瘤坏死因子α（TNF-α）]（P≤0.05）。在体外RSV刺激的PBMC培养物中，母乳喂养的婴儿与喂养含2'-FL配方奶的两组婴儿无差异，但与喂养对照配方奶的婴儿相比，其TNF-α浓度低31%，干扰素γ（IFN-γ）浓度低54%（P≤0.05），且IL-1ra（25%）、IL-6（38%）（未校正P≤0.05）和IL-1β（30%）（未校正P = 0.06）有降低趋势。
我们的数据表明，喂养添加2'-FL配方奶的婴儿血浆和体外炎症细胞因子水平较低，与母乳喂养参考组相似。该试验在clinicaltrials.gov注册，注册号为NCT01808105。
