Antiviral oxysterols are present in human milk at diverse stages of lactation

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 193; p. 105424
• Main Authors: Civra, Andrea, Leoni, Valerio, Caccia, Claudio, Sottemano, Stefano, Tonetto, Paola, Coscia, Alessandra, Peila, Chiara, Moro, Guido E., Gaglioti, Pietro, Bertino, Enrico, Poli, Giuseppe, Lembo, David
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2019; Elsevier BV
• Subjects: Adult; Animals; Antiviral; Antiviral activity; Antiviral Agents - analysis; Antiviral Agents - blood; Antiviral Agents - pharmacology; Baby foods; Breast feeding; Breast milk; Breastfeeding & lactation; Cattle; Cell Line; Chlorocebus aethiops; Cholesterol; Colostrum; Colostrum - chemistry; Enzymatic synthesis; Female; Gas chromatography; Humans; Immune response; Innate immunity; Lactation; Mass spectroscopy; Maternal milk; Milk, Human - chemistry; Oxidation; Oxysterols; Oxysterols - analysis; Oxysterols - blood; Oxysterols - pharmacology; Rhinovirus; Rhinovirus - drug effects; Rotavirus; Rotavirus - drug effects; Sterols; C; BM; 7KC; DMEM; S; FFU; 24SHC; 27HC; Oxysterols; HRhV; EC50; Antiviral; MFGM; Rhinovirus; MM; GC–MS; Maternal milk; Rotavirus; COP; MOI; 25HC; HRoV; CS; 7βOHC; TM; SEM; Colostrum; MAP
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2019.105424

•This study discloses new antiviral components of human milk.•24HC, 25HC, and 27HC are oxysterols present in human milk at any stage of lactation.•27HC content in colostrum is remarkably higher than that of 24HC and 25HC.•27HC concentrations in colostrum are potentially active against HRoV and HRhV. Oxysterols are cholesterol oxidation derivatives. Those containing an additional hydroxyl group on the side chain of the cholesterol molecule result from a physiological enzymatic synthesis and include the majority of oxysterols present in the circulation. Among these, 25-hydroxycholesterol (25OHC) and 27-hydroxycholesterol (27OHC) are characterized by a broad antiviral activity and are now considered involved in the innate immune response against viruses. Despite the emerging role of these sterols in the innate antiviral defences, no data are available on their presence in human breast milk (BM) to date. In this study, we investigated the content of oxysterols of enzymatic synthesis in BM of twelve donor mothers at different stages of lactation (i.e. in colostrum, transitional milk, and mature milk) by gas chromatography-mass spectrometry analysis. The side-chain oxysterols 25OHC, 27OHC, and 24S-hydroxycholesterol (24SOHC) were actually present in BM in all stages of lactation, but the concentration of 27OHC showed a remarkable peak in colostrum. Antiviral assays revealed that all the colostrum samples contained 27OHC concentrations that were active in vitro against two relevant pediatric viral pathogens: the human rotavirus and the human rhinovirus. Overall, this study discloses new antiviral components of BM and suggests a passive transfer of these protective factors to the infant via breastfeeding, especially in the first few days of lactation.