Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review

Abstract

Background Human milk (HM) transforming growth factor beta (TGF‐β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF‐β levels are associated with allergic outcomes. Objective We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF‐β and allergic outcomes in children. Methods Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. Results A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF‐β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF‐β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF‐β2 on eczema. Meta‐analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. Conclusion and clinical relevance In contrast with previous findings, we did not find strong evidence of associations between HM TGF‐β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF‐β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF‐β in combination with other HM immune markers, microbiome and oligosaccharides are required.

Bioactive Factors in Human Breast Milk Attenuate Intestinal Inflammation during Early Life

“…The TGF-β family comprise the most abundant cytokines of human milk. The highest levels are present in colostrum and decline substantially by 4-6 weeks of life [97]. They include 3 isoforms, with TGF-β2 being the most predominant.…”

Novel approach to visualize the inter-dependencies between maternal sensitization, breast milk immune components and human milk oligosaccharides in the LIFE Child cohort

“…Currently, the literature has yet to reach a consensus on whether any breast milk component or a specific profile for breast milk composition is associated with allergy risk, allergic sensitization, or allergic disease in the infant [7,8]. Numerous studies have associated breast milk levels of transforming growth factors (TGF) such as TGF-ß1, TGF-ß2 and/or levels of immunoglobulin (Ig) A with allergy in infants or mothers [9][10][11], yet a recent review suggests that the data were not robust enough to reach a conclusion on TGF-ß1 and 2 [12]. Similarly, breast milk fatty acids such as polyunsaturated fatty acid (PUFA) and polyunsaturated fatty acid (MUFA) levels or ratio have been found inversely associated with allergy risk in the infants while others did not found any association [13].…”

Does Caesarean Section or Preterm Delivery Influence TGF-β2 Concentrations in Human Colostrum?

“…On the other hand, there are also data suggesting that higher levels of TGF-β2 may be related to NEC [18]. Furthermore, systemic review from 2019 suggests an increased risk of allergic diseases in infants whose mothers had higher levels of TGF-β2 in milk, but due to differences in studies' methodology and outcomes, this issue remains unclear [19]. Recent studies showed also the correlation between the concentration of TGF-β2 in HC and diversity of gut microbiota [20].…”