Surprisingly little is known about the effect of breastfeeding on the infant's immune system development. Systematic reviews have suggested the role of breastfeeding in the prevention against asthma, autoimmune diseases, inflammatory bowel disease, and childhood leukemia. However, studies on atopic disease suffer from reverse causation, small size, and those assessing food allergy (FA) have often relied on parent-reported outcomes. Randomized controlled trials (RCTs) are not possible for ethical reasons. In addition, epidemiological studies have not considered that there is a large interindividual variation in human milk (HM) composition and feeding at the breast versus pumped HM potentially impacting the effect of breastfeeding between mothers. While prevention strategies such as early introduction of highly allergenic food are impactful in preventing peanut and egg allergies, implementation of early introduction guidelines has been slow, and many infants are already sensitized by 4-6 months of age. To be more effective, primary prevention strategies must commence much earlier, during breastfeeding. There are studies that imply a definitive effect of breastfeeding on the gut microbiome and regulatory T cells (Tregs) as well as a higher rate of FA in populations with historically low rates of breastfeeding. These provide a strong rationale for assessing the effect of feeding HM in the context of HM composition and mode of feeding on immune development. The lack of well-conducted, large studies assessing the role of breastfeeding and HM composition in the development of immune system development is a significant gap when designing prevention strategies.
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