Human Milk MicroRNAs in the Development of Infant’s Immune System: A Systematic Review
Keywords:
Human milk, microRNA, infant, immune system, immunological functionsAbstract
Exclusive breastfeeding practice is relatively low among children below six months of age, despite the countless advantages provided by human milk. Improving and enhancing the immune system of the infants are important as their immune system is not completely developed yet in the early life. Breast milk or human milk is relatively abundant with bioactive components and nutrients and offers a complete source of food to the infants. The bioactive components of human milk are believed to provide infants with great protection. Currently, researchers discover the roles of microRNAs in human milk of humans towards proper immune system development of the infants. This systematic review aims to access and collect data on the diverse immune-related microRNAs in the human milk and their immunoregulatory functions. To obtain related articles pertaining to the human milk microRNAs, a systematic search was conducted by using three relevant databases namely Science Direct, Scopus and PubMed using appropriate keywords for the papers published in English between 2010 and 2019. The included papers in this systematic review were appraised using Crowe Critical Appraisal Tool (CCAT). From 314 potential papers identified initially, five papers met the inclusion criteria for this review. All papers were of moderate to high quality. Discussion: This systematic review has provided valuable information on numerous immune-related microRNAs that can be found in human milk, including their immunological functions. The most abundantly expressed microRNAs include miR-146b, miR-148a, and miR-146a. The findings suggest that the microRNAs found in human milk along with their immunoregulatory functions were crucial in strengthening immune system of the infants.
References
Fauzi R, Mohamed CR, Ismail R, Othman MS. The effectiveness of breastfeeding intervention on breastfeeding exclusivity and duration among primiparous mothers in Hospital Universiti Sains Malaysia. The Malaysian Journal of Medical Sciences 2018; 25(1):53–66.
WHO. Exclusive breastfeeding for optimal growth, development and health of infants. Retrieved September 19, 2020 from https://www.who.int/elena/titles/exclusive_breastfeeding/en/#:~:text=Breastfeeding%20has%20many%20health%20benefits%20for%20both%20the%20mother%20and%20infant.&text=Exclusive%20breastfeeding%20means%20that%20the,of%20vitamins%2C%20minerals%20or%20medicines.
Abdul Rashid A, Shamsuddin NH, Raja Malik Ridhuan RDA, Sallahuddin NA, Devaraj NK. Breastfeeding practice, support, and self-efficacy among working mothers in a rural health clinic in Selangor. Retrieved September 19, 2020 from https://www.researchgate.net/publication/326551995_Breastfeeding_Practice_Support_and_Self_Efficacy_Among_working_Mothers_in_a_Rural_Health_Clinic_in_Selangor
Le Doare K, Holder B, Bassett A, Pannaraj PS. Mother’s milk: a purposeful contribution to the development of the infant microbiota and immunity. Front. Immunol. 2018; 9:361.
Crowe M. Crowe Critical Appraisal Tool (CCAT) User Guide. Retrieved September 19, 2020 from https://conchra.com.au/wp-content/uploads/2015/12/CCAT-user-guide-v1.4.pdf
PRISMA FLOW DIAGRAM. Retrieved September 19, 2020 from http://prisma-statement.org/PRISMAStatement/FlowDiagram.aspx
Kosaka N, Izumi H, Sekine K, Ochiya T. MicroRNA as a new immune-regulatory agent in human milk. Silence 2010; 1(1), 7.
Zhou Q, Li M, Wang X, Li Q, Wang T, et al. Immune-related microRNAs are abundant in human milk exosomes. Int. J Biol. Sci. 2012; 8(1), 118–123.
Mirza AH, Kaur S, Nielsen LB, Størling J, Yarani R, et al. Human milk-derived extracellular vesicles enriched in exosomes from mothers with type 1 diabetes contain aberrant levels of microRNAs. Front. Immunol. 2019; 10, 2543.
Shiff YE, Reif S, Marom R, Shiff K, Reifen R, et al. MiRNA-320a is less expressed and miRNA-148a more expressed in preterm human milk compared to term human milk. J Funct. Foods 2019; 57, 68-74.
Perri M, Lucente M, Cannataro R, De Luca IF, Gallelli L, et al. Variation in immune-related micrornas profile in human milk amongst lactating women. MicroRNA (Shariqah United Arab Emirates) 2018; 7(2), 107–114.
Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr. Clin. North Am. 2013; 60(1), 49–74.
Alsaweed M, Hartmann PE, Geddes DT, Kakulas F. MicroRNAs in breastmilk and the lactating breast: potential immunoprotectors and developmental regulators for the infant and the mother. Int. J Environ. Res. Public Health 2015; 12(11), 13981–14020.
Benmoussa A, Provost P. Milk microRNAs in health and disease. Comprehensive Reviews in Food Science and Food Safety 2019; 18: 703–722
Lu LF, Liston A. MicroRNA in the immune system, microRNA as an immune system. Immunology 2009; 127(3), 291–298.
Simpson MR, Brede G, Johansen J, Johnsen R, Storrø O, et al. Human milk miRNA, maternal probiotic supplementation and atopic dermatitis in offspring. PLOS ONE 2015; 10(12), e0143496.
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