A systematic review of the importance of milk TGF-β on immunological outcomes in the infant and young child

Cytokines in milk like transforming growth factor-beta (TGF-beta) have been shown to induce oral tolerance in experimental animal studies. However, human studies are less consistent with these findings. The primary objective of this review was to conduct a systematic review of published studies on the association between TGF-beta identified in human milk and immunological outcomes in infancy and early childhood. Human prospective clinical studies were identified through MEDLINE, CAB Abstracts, Biological Abstracts and Scopus. Selection criteria included: well described populations of mothers and infants, time of milk sampling, immunological outcome measures and analytical methods of TGF-beta determination. We considered a wide range of immunological outcomes in infancy and early childhood, such as wheeze, atopy, eczema and the immunoglobulin switch. Twelve human studies were included in the review and 67% showed a positive association with TGF-beta 1 or TGF-beta 2 demonstrating protection against allergy-related outcomes in infancy and early childhood. High variability in concentrations of TGF-beta was noted between and within studies, some of it explained by maternal history of atopy or by consumption of probiotics. Human milk TGF-beta appears to be essential in developing and maintaining appropriate immune responses in infants and may provide protection against adverse immunological outcomes, corroborating findings from experimental animal studies. Further large clinical studies in diverse human populations are indicated to confirm these results.