Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Örebro University Food and Health Programme, School of Medical Sciences, Örebro University, Örebro, Sweden.
Front Immunol. 2021 Sep 1;12:725323. doi: 10.3389/fimmu.2021.725323. eCollection 2021.
Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied.
PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.
母乳是新生儿营养和水分的主要来源，但在儿童的首次免疫防御中也起着重要作用。此外，一些母乳因素与生命后期的免疫相关健康结果有关，包括免疫球蛋白、细胞因子、趋化因子、生长因子，以及最近的非编码 RNA（ncRNA）种类。在这项系统评价中，我们全面总结了目前关于人乳中内源性 ncRNA 的文献。确定了 30 项相关研究，尽管大多数研究都集中在 microRNAs（miRNAs）上，但有证据表明，母乳中含有大量 RNA，包括长编码 RNA、环状 RNA 以及其他短 RNA 和碎片化 tRNA 和 rRNA。在研究 miRNA 的研究中，miR-148a-3p、miR-30a/d-5p、miR-22-3p、miR-146b-5p、miR-200a/c-3p 和 let-7 miRNAs 的 5p 端通常是母乳细胞、脂质和脱脂奶部分中排名前 10 的 miRNA 之一。方法学差异和小样本量限制了确定哪些产妇和婴儿特征影响 miRNA 谱的可能性。高表达的 miRNA 通常在泌乳阶段、乳成分、产妇和婴儿特征或婴儿生长和健康方面较为相似。尽管如此，个别研究还是确定了 miRNA 表达水平的潜在差异，这需要通过未来的研究来证实。在几项研究中还考虑了 miRNA 的稳定性、摄取和生理功能。母乳中的 miRNA 相对能抵抗一系列恶劣条件，摄取实验表明，含有 miRNA 和环状 RNA 的细胞外囊泡可以被肠道上皮细胞摄取。尽管关于母乳 miRNA 的功能作用的证据有限，但预测的功能范围从代谢和生物合成过程到信号通路、细胞黏附、通讯、生长和分化。最后，这项系统评价强调了一些方法学挑战和知识空白，可以帮助指导该领域的未来研究。特别是，进一步研究不同乳成分中 miRNA 的生物利用度，并对其他大部分未被研究的 ncRNA 进行特征描述非常重要。
