Jorgensen Josh M, Young Rebecca, Ashorn Per, Ashorn Ulla, Chaima David, Davis Jasmine C C, Goonatilleke Elisha, Kumwenda Chiza, Lebrilla Carlito B, Maleta Kenneth, Sadalaki John, Totten Sarah M, Wu Lauren D, Zivkovic Angela M, Dewey Kathryn G
Department of Nutrition, University of California, Davis, Davis, CA, USA.
Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Curr Dev Nutr. 2021 Apr 29;5(5):nzab072. doi: 10.1093/cdn/nzab072. eCollection 2021 May.
Human milk oligosaccharides (HMOs) and bioactive proteins likely benefit infant health, but information on these relations is sparse.
We aimed to examine associations of milk content of HMOs and bioactive proteins with incidence and longitudinal prevalence of infant morbidity (any illness, fever, diarrhea, acute respiratory infection, and loss of appetite) and markers of inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)]. These are secondary analyses of a randomized controlled trial.
Breast milk samples at 6 mo postpartum ( = 659) were analyzed to quantify absolute abundance of HMOs, relative abundance of fucosylated HMOs, sialylated HMOs, and 51 individual HMOs, and concentrations of 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of these constituents with infant morbidity from 6 to 7 and 6 to 12 mo, and CRP and AGP at 6 and 18 mo, considering maternal secretor status [presence or absence of the functional enzyme encoded by the fucosyltransferase 2 gene () ] and adjusting for covariates and multiple hypothesis testing.
In secretors there were positive associations between total HMOs and longitudinal prevalence of fever ( = 0.032), between fucosylated HMOs and incidence of diarrhea ( = 0.026), and between lactoferrin and elevated CRP at 18 mo ( = 0.011). In nonsecretors, there were inverse associations between lactoferrin and incidence of fever ( = 0.007), between osteopontin and longitudinal prevalence of lost appetite ( = 0.038), and between fucosylated HMOs and incidence of diarrhea ( = 0.025), lost appetite ( = 0.019), and concentrations of AGP and CRP at 6 mo ( = 0.001 and 0.010); and positive associations between total HMOs and incidence of lost appetite ( = 0.024) and elevated CRP at 18 mo ( = 0.026), between lactalbumin and incidence of diarrhea ( = 0.006), and between lactoferrin and elevated CRP at 18 mo ( = 0.015).
Certain HMOs and bioactive proteins were associated with infant morbidity and inflammation, particularly in nonsecretors. Further research is needed to elucidate the causality of these relations.This trial was registered at clinicaltrials.gov as NCT01239693.
人乳寡糖（HMOs）和生物活性蛋白可能有益于婴儿健康，但关于这些关系的信息较少。
我们旨在研究HMOs和生物活性蛋白的乳汁含量与婴儿发病率（任何疾病、发热、腹泻、急性呼吸道感染和食欲不振）的发生率及纵向患病率以及炎症标志物[C反应蛋白（CRP）和α-1-酸性糖蛋白（AGP）]之间的关联。这些是一项随机对照试验的二次分析。
对产后6个月时的母乳样本（n = 659）进行分析，以量化HMOs的绝对丰度、岩藻糖基化HMOs、唾液酸化HMOs和51种个体HMOs的相对丰度，以及6种生物活性蛋白（乳白蛋白、乳铁蛋白、溶菌酶、抗胰蛋白酶、IgA和骨桥蛋白）的浓度。我们研究了这些成分与婴儿在6至7个月和6至12个月时的发病率，以及在6个月和18个月时的CRP和AGP之间的关联，同时考虑了母亲的分泌状态[岩藻糖基转移酶2基因（FUT2）编码的功能性酶的有无]，并对协变量和多重假设检验进行了调整。
在分泌者中，总HMOs与发热的纵向患病率之间存在正相关（P = 0.032），岩藻糖基化HMOs与腹泻的发生率之间存在正相关（P = 0.026），乳铁蛋白与18个月时CRP升高之间存在正相关（P = 0.011）。在非分泌者中，乳铁蛋白与发热的发生率之间存在负相关（P = 0.007），骨桥蛋白与食欲不振的纵向患病率之间存在负相关（P = 0.038），岩藻糖基化HMOs与腹泻的发生率（P = 0.025）、食欲不振的发生率（P = 0.019）以及6个月时AGP和CRP的浓度之间存在负相关（P = 0.001和0.010）；总HMOs与食欲不振的发生率（P = 0.024）和18个月时CRP升高之间存在正相关（P = 0.026），乳白蛋白与腹泻的发生率之间存在正相关（P = 0.006），乳铁蛋白与18个月时CRP升高之间存在正相关（P = 0.015）。
某些HMOs和生物活性蛋白与婴儿发病率和炎症有关，尤其是在非分泌者中。需要进一步研究来阐明这些关系的因果关系。本试验已在clinicaltrials.gov注册，注册号为NCT01239693。
