NIH grant: Systems Biology of Early Atopy: Role of Human Milk (SunBEAm-Milk) (1U01AI198302-01)

retained text

NIH grant 1U01AI198302-01: Systems Biology of Early Atopy: Role of Human Milk (SunBEAm-Milk)
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Kirsi  Jarvinen-Seppo. Award: $649089.
Start: 2026-06-18T00:00:00.
Surprisingly little is known about the effect of breastfeeding (BF) on infant immune system development besides
an effect on the gut microbiome, but its impact on metabolites and Tregs could support protection against food
allergy (FA). BF is currently recommended to prevent the development of allergic diseases, especially
asthma/recurrent wheezing and AD in early childhood, but firm conclusions could not be drawn regarding FA
due to high heterogeneity and low quality of studies. Reverse causation, recall bias and the poor accuracy of
outcome assessment are significant limitations. Most are inadequately powered to specific FA; however, a recent
study showed that exclusively BF infants had lower odds of egg, sesame, and peanut allergies. Importantly,
immunomodulatory composition of HM varies between mothers, which has not been taken into consideration.
 For over two decades we have been developing methods to assess immunomodulatory factors in the
complex matrix of HM and their association with infant FA. We have shown that high levels of HM total and
specific IgA are associated with protection against cow’s milk allergy, but it is unclear whether HM IgA is
responsible for or is a biomarker of the vertical transfer of protection. Infant fecal and systemic IgA levels during
breastfeeding and after weaning are also elevated in infants at low risk for atopic disease raising the question of
whether HM factors such as cytokines can promote IgA production in infants. Consistent with this, we showed
that HM cytokines, such as APRIL, induce IgA production in naïve infant B cells, and infants receiving HM with
higher levels of APRIL had lower incidence of allergic disease. Finally, lower levels of several HM fatty acids
including short-chain fatty acids and DHA were associated with FA. While some these factors were are
associated with maternal atopic disease, several of them are not and suggest a role for diet instead.
 The System Biology of Early Atopy (SunBEAm) population-based cohort of 2500 mother-infant pairs is
>50% recruited and provides an unprecedented opportunity to assess association of HM feeding and immune
factors in HM with development of infant immune system and FA/AD. The Common Sample comprises a subset
of 100 dyads with FA, 100 with FA+AD, 100 with AD, 100 with no FA or AD and more extensively profiled
biological data. Utilizing all 2-month HM samples available in the Common Sample, we will assess levels of
immune factors in HM and their association with maternal/infant characteristics (Aim 1). Utilizing data from the
whole cohort, we will assess the association between HM vs formula feeding on well-defined FA/AD further
adjusted based on high vs low levels of HM immune components in the Common Sample (Aim 2b). Finally, we
will examine the immune cell and epithelial effects of HM on infant immune markers and intestinal organoids
(Aim 3). Key findings will be validated in an independent birth cohort.
 The ultimate goal is to uncover protective properties of BF and HM in FA and subsequent design of
policies and prevention strategies to address the increasing rates of FA.

document fetched 2026-06-28 13:47