Therapeutic use of human milk for high-risk neonates and immunosuppressed patients

Abstract

Breastfeeding represents an ingenious immunological integration between a mother and infant that has evolved over millennia to nourish and protect infants from infectious diseases during this critical period of immune vulnerability. Human milk contains a wide variety of bioactive factors with anti-infective properties, in general, in higher concentrations in colostrum - which are: oligosaccharides, lysozyme, lactoferrin, lactoperoxidase, mucin, defensins, cytokines, chemokines, hormones and growth factors, complement system proteins, nucleic acids, including microRNAs, viable leukocytes, among many others. But certainly, the most studied factors have been IgA class antibodies, with colostrum being the secretion with the highest concentrations of this immunoglobulin class, which is present in its polymeric form associated with the secretory component, being called secretory IgA (SIgA). These factors interact with each other and also with the mucosa of the digestive and upper respiratory tract of the infant, providing effective passive immunity and growth and differentiation factors, in addition to favoring the composition of a healthy intestinal microbiota, that is, with relevance for the current and future child health. It is remarkable the increase in interest of the immunological aspects of human milk in the medical literature in recent years, particularly during the COVID-19 pandemic, which has been one of our group's research interests since the early 1980s (55 publications and 23 PhD and Masters` dissertations). The anti-infectious protection of newborns (NB) and infants by breastfeeding is already well established by numerous epidemiological and clinical studies and, more recently, there has been a growing interest in the investigation of the therapeutic potential of this secretion for NBs who cannot suck (colostrum therapy) and patients with immunological disorders, in whom evidence of its protective effect is already available. Due to the increase in antibody concentrations, vaccination of pregnant and/or lactating women can further increase the protective potential of milk for certain infections.In this proposal we intend to evaluate the therapeutic potential of human milk: i) in NBs undergoing surgery immediately after birth to correct malformations of the digestive tract or abdominal wall (subproject 1); ii) use of the IgA preparation by nasal route for immunosuppressed adolescents and young adults with chronic rhinosinusopathy (subproject 2), iii) anti-SARS-CoV-2 antibody levels in colostrum and milk from immunized mothers also aiming its use in immunodeficients (subproject 3). The other subprojects have a basic investigation character and aim to explore the polyreactivity of IgA aiming at the construction of monoclonal antibodies (subproject 4) and the analysis of microRNAs in milk from mothers of term and preterm newborns (with or without malformations of the digestive tract), in order to explore its future potential for therapeutic use in NB at risk (subproject 5). (AU)