Table_5_Human Milk Oligosaccharides and Associations With Immune-Mediated Disease and Infection in Childhood: A Systematic Review.DOCX

Complex sugars found in breastmilk, human milk oligosaccharides (HMOs), may assist in early-life immune programming and prevention against infectious diseases. This study aimed to systematically review the associations between maternal levels of HMOs and development of immune-mediated or infectious diseases in the offspring. PubMed and EMBASE databases were searched (last search on 22 February 2018) according to a predetermined search strategy. Original studies published in English examining the effect of HMOs on immune-mediated and infectious disease were eligible for inclusion. Of 847 identified records, 10 articles from 6 original studies were included, with study quality ranging from low to high. Of three studies to examine allergic disease outcomes, one reported a protective effect against cow’s milk allergy (CMA) by 18 months of age associated with lower lacto-N-fucopentaose (LNFP) III concentrations (OR: 6.7, 95% CI 2.0–22). Another study found higher relative abundance of fucosyloligosaccharides was associated with reduced diarrhea incidence by 2 years, due to (i) stable toxin-E. coli infection (p = 0.04) and (ii) “all causes” (p = 0.042). Higher LNFP-II concentrations were associated with (i) reduced cases of gastroenteritis and respiratory tract infections at 6 weeks (p = 0.004, p = 0.010) and 12 weeks (p = 0.038, p = 0.038) and (ii) reduced HIV transmission (OR: 0.45; 95% CI: 0.21–0.97) and mortality risk among HIV-exposed, uninfected infants (HR: 0.33; 95% CI: 0.14–0.74) by 24 months. Due to heterogeneity of the outcomes reported, pooling of results was not possible. There was limited evidence that low concentrations of LNFP-III are associated with CMA and that higher fucosyloligosaccharide levels protect infants against infectious disease. Further research is needed.

母乳中所含的复合糖类——人乳低聚糖（human milk oligosaccharides, HMOs），或可助力子代早期免疫编程，并预防感染性疾病。本研究旨在系统综述母体人乳低聚糖水平与子代免疫介导性疾病及感染性疾病发生之间的关联。研究按照预先设定的检索策略，对PubMed及EMBASE数据库进行了检索（最后一次检索时间为2018年2月22日）。纳入标准为已发表的英文原创研究，且探讨人乳低聚糖对免疫介导性疾病及感染性疾病的影响。在检索得到的847条记录中，最终纳入来自6项原创研究的10篇文献，研究质量跨度从低至高。在3项探讨变应性疾病转归的研究中，有1项报告称，子代在18月龄时较低的乳-N-岩藻五糖（lacto-N-fucopentaose, LNFP）III浓度，可对牛奶过敏（cow’s milk allergy, CMA）产生保护作用（比值比（Odds Ratio, OR）=6.7，95%置信区间（Confidence Interval, CI）为2.0~22）。另有研究发现，岩藻糖低聚糖相对丰度较高与子代2岁时腹泻发病率降低相关，具体可归因于（i）产稳定毒素大肠杆菌感染（p=0.04）以及（ii）"各类病因"（p=0.042）。较高的乳-N-岩藻五糖II（lacto-N-fucopentaose II, LNFP-II）浓度与以下结局相关：（i）在子代6周龄（p=0.004，p=0.010）及12周龄（p=0.038，p=0.038）时，胃肠炎与呼吸道感染病例数减少；（ii）在24月龄时，HIV暴露未感染婴儿的HIV传播风险降低（比值比（Odds Ratio, OR）=0.45；95%置信区间（Confidence Interval, CI）为0.21~0.97）以及死亡风险降低（风险比（Hazard Ratio, HR）=0.33；95%置信区间（Confidence Interval, CI）为0.14~0.74）。由于所报告的研究结局存在异质性，无法对研究结果进行合并分析。现有证据有限，表明低浓度的乳-N-岩藻五糖III与牛奶过敏相关，且较高的岩藻糖低聚糖水平可保护婴儿免受感染性疾病侵袭。未来仍需开展更多相关研究。