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Immune Response of Neonates Born to Mothers Infected With SARS-CoV-2.
Conti, MG, Terreri, S, Piano Mortari, E, Albano, C, Natale, F, Boscarino, G, Zacco, G, Palomba, P, Cascioli, S, Corrente, F, et al
JAMA network open. 2021;(11):e2132563
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Abstract
IMPORTANCE Although several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. OBJECTIVE To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. EXPOSURES Maternal infection with SARS-CoV-2 in late pregnancy. MAIN OUTCOMES AND MEASURES The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain-specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigen-antibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. RESULTS In total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months' follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike protein-specific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. CONCLUSIONS AND RELEVANCE In this cohort study, SARS-CoV-2 spike-specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the newborn via breastmilk secretory IgA but also actively stimulate and train the neonatal immune system via breastmilk immune complexes.
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Role of IgA in the early-life establishment of the gut microbiota and immunity: Implications for constructing a healthy start.
Guo, J, Ren, C, Han, X, Huang, W, You, Y, Zhan, J
Gut microbes. 2021;(1):1-21
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Abstract
Colonization and maturation of the gut microbiota (GM) during early life is a landmark event that fundamentally influences the (early) immunity and later-life health of various mammals. This is a delicate, systematic process that is biologically actively regulated by infants and their mothers, where (secretory) IgA, an important regulator of microbes found in breast milk and generated actively by infants, may play a key role. By binding to microbes, IgA can inhibit or enhance their colonization, influence their gene expression, and regulate immune responses. IgA dysfunction during early life is associated with disrupted GM maturation and various microbe-related diseases, such as necrotizing enterocolitis and diarrhea, which can also have a lasting effect on GM and host health. This review discusses the process of early GM maturation and its interaction with immunity and the role of IgA (focusing on milk secretory IgA) in regulating this process. The possible application of this knowledge in promoting normal GM maturation processes and immune education has also been highlighted.
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Human Milk Drives the Intimate Interplay Between Gut Immunity and Adipose Tissue for Healthy Growth.
van den Elsen, LWJ, Verhasselt, V
Frontiers in immunology. 2021;:645415
Abstract
As the physiological food for the developing child, human milk is expected to be the diet that is best adapted for infant growth needs. There is also accumulating evidence that breastfeeding influences long-term metabolic outcomes. This review covers the potential mechanisms by which human milk could regulate healthy growth. We focus on how human milk may act on adipose tissue development and its metabolic homeostasis. We also explore how specific human milk components may influence the interplay between the gut microbiota, gut mucosa immunity and adipose tissue. A deeper understanding of these interactions may lead to new preventative and therapeutic strategies for both undernutrition and other metabolic diseases and deserves further exploration.
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Biotechnological Production of 2'-Fucosyllactose: A Prevalent Fucosylated Human Milk Oligosaccharide.
Zhou, W, Jiang, H, Wang, L, Liang, X, Mao, X
ACS synthetic biology. 2021;(3):447-458
Abstract
Human milk oligosaccharide (HMO) is a key component of human milk carbohydrates and is closely related to the nutrition and health benefits of breastfeeding in infants. 2'-Fucosyllactose (2'-FL) is the most abundant fucosylated HMO, which has remarkable value in nutrition and medicine, such as suppressing pathogen infection, regulating intestinal flora, and boosting immunity. However, 2'-FL production via the method of extraction or chemical synthesis cannot meet its large demand, and as a result, environmentally friendly and efficient biotechnological approaches, including in vitro enzymatic synthesis and microbial cell factory production, have been developed and applied to its commercialized production. This review introduces, summarizes, and discusses the recent advances in the biotechnological production of 2'-FL. Furthermore, future research directions for the biotechnological production of 2'-FL as well as the strategies to further improve its concentration are highlighted and discussed.
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Multifunctional Benefits of Prevalent HMOs: Implications for Infant Health.
Hill, DR, Chow, JM, Buck, RH
Nutrients. 2021;(10)
Abstract
Breastfeeding is the best source of nutrition during infancy and is associated with a broad range of health benefits. However, there remains a significant and persistent need for innovations in infant formula that will allow infants to access a wider spectrum of benefits available to breastfed infants. The addition of human milk oligosaccharides (HMOs) to infant formulas represents the most significant innovation in infant nutrition in recent years. Although not a direct source of calories in milk, HMOs serve as potent prebiotics, versatile anti-infective agents, and key support for neurocognitive development. Continuing improvements in food science will facilitate production of a wide range of HMO structures in the years to come. In this review, we evaluate the relationship between HMO structure and functional benefits. We propose that infant formula fortification strategies should aim to recapitulate a broad range of benefits to support digestive health, immunity, and cognitive development associated with HMOs in breastmilk. We conclude that acetylated, fucosylated, and sialylated HMOs likely confer important health benefits through multiple complementary mechanisms of action.
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The Immune System in Human Milk: A Historic Perspective.
Goldman, AS, Chheda, S
Annals of nutrition & metabolism. 2021;(4):189-196
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Abstract
BACKGROUND Human milk contains a remarkable array of immunological agents that evolved over millions of years to protect the recipient human infant. Furthermore, much of the protection persists long after weaning. However, the scientists who first discovered some components of this immune system have rarely been acknowledged. SUMMARY The scientists who made many fundamental immunological discoveries concerning the immune system in human milk include Alfred François Donné, Paul Ehrlich, Lars Å. Hanson, and Jules Bordet. Based upon their discoveries, a wealth of antimicrobial, anti-inflammatory, and immunomodulating agents, and living, activated leukocytes in human milk were later revealed during the last half of the 20th and the first part of the 21st century. Moreover, it was found that human milk enhances the colonization of commensal bacteria that aid to protect the human infant. Key Message: Their discoveries helped to revitalize breastfeeding in industrialized countries during the past several decades.
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Cohort profile: Study on Zika virus infection in Brazil (ZIKABRA study).
Calvet, GA, Kara, EO, Landoulsi, S, Habib, N, Bôtto-Menezes, CHA, Franca, RFO, Neto, AM, Castilho, MDC, Fernandes, TJ, Pereira, GF, et al
PloS one. 2021;(1):e0244981
Abstract
Zika virus (ZIKV) has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood to one week after the onset of symptoms and has been found to persist longer in urine and semen. To better understand virus dynamics, a prospective cohort study was conducted in Brazil to assess the presence and duration of ZIKV and related markers (viral RNA, antibodies, T cell response, and innate immunity) in blood, semen, saliva, urine, vaginal secretions/menstrual blood, rectal swab and sweat. The objective of the current manuscript is to describe the cohort, including an overview of the collected data and a description of the baseline characteristics of the participants. Men and women ≥ 18 years with acute illness and their symptomatic and asymptomatic household contacts with positive reverse transcriptase-polymerase chain reaction test for ZIKV in blood and/or urine were included. All participants were followed up for 12 months. From July 2017 to June 2019, a total of 786 participants (284 men, 502 women) were screened. Of these, 260 (33.1%) were enrolled in the study; index cases: 64 men (24.6%), 162 (62.3%) women; household contacts: 12 men (4.6%), 22 (8.5%) women. There was a statistically significant difference in age and sex between enrolled and not enrolled participants (p<0.005). Baseline sociodemographic and medical data were collected at enrollment from all participants. The median and interquartile range (IQR) age was 35 (IQR; 25.3, 43) for men and 36.5 years (IQR; 28, 47) for women. Following rash, which was one of the inclusion criteria for index cases, the most reported symptoms in the enrollment visit since the onset of the disease were fever, itching, arthralgia with or without edema, non-purulent conjunctivitis, headache, and myalgia. Ten hospitalizations were reported by eight patients (two patients were hospitalized twice) during follow up, after a median of 108 days following symptom onset (range 7 to 266 days) and with a median of 1.5 days (range 1 to 20 days) of hospital stay. A total of 4,137 visits were performed, 223 (85.8%) participants have attended all visits and 37 (14.2%) patients were discontinued.
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In the Age of Viral Pandemic, Can Ingredients Inspired by Human Milk and Infant Nutrition Be Repurposed to Support the Immune System?
Brink, LR, Chichlowski, M, Pastor, N, Thimmasandra Narayanappa, A, Shah, N
Nutrients. 2021;(3)
Abstract
In 2020, with the advent of a pandemic touching all aspects of global life, there is a renewed interest in nutrition solutions to support the immune system. Infants are vulnerable to infection and breastfeeding has been demonstrated to provide protection. As such, human milk is a great model for sources of functional nutrition ingredients, which may play direct roles in protection against viral diseases. This review aims to summarize the literature around human milk (lactoferrin, milk fat globule membrane, osteopontin, glycerol monolaurate and human milk oligosaccharides) and infant nutrition (polyunsaturated fatty acids, probiotics and postbiotics) inspired ingredients for support against viral infections and the immune system more broadly. We believe that the application of these ingredients can span across all life stages and thus apply to both pediatric and adult nutrition. We highlight the opportunities for further research in this field to help provide tangible nutrition solutions to support one's immune system and fight against infections.
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COVID-19 mRNA Vaccination in Lactation: Assessment of Adverse Events and Vaccine Related Antibodies in Mother-Infant Dyads.
Golan, Y, Prahl, M, Cassidy, AG, Gay, C, Wu, AHB, Jigmeddagva, U, Lin, CY, Gonzalez, VJ, Basilio, E, Chidboy, MA, et al
Frontiers in immunology. 2021;:777103
Abstract
BACKGROUND Data regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines. METHODS From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose). RESULTS No severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation. CONCLUSIONS COVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.
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Non-Coding RNAs in Human Breast Milk: A Systematic Review.
Tingö, L, Ahlberg, E, Johansson, L, Pedersen, SA, Chawla, K, Sætrom, P, Cione, E, Simpson, MR
Frontiers in immunology. 2021;:725323
Abstract
UNLABELLED Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied. SYSTEMATIC REVIEW REGISTRATION PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.