scholarly journals Human Cytomegalovirus (HCMV) Reactivation in the Mammary Gland Induces a Proinflammatory Cytokine Shift in Breast Milk

2020 ◽  
Vol 8 (2) ◽  
pp. 289 ◽  
Author(s):  
Tabea Rabe ◽  
Katrin Lazar ◽  
Christoffer Cambronero ◽  
Rangmar Goelz ◽  
Klaus Hamprecht

A locally restricted human cytomegalovirus (HCMV) reactivation in the mammary gland commonly occurs in nearly every IgG-seropositive breastfeeding mother. This unique phenomenon can therefore be used to study the reactivation process in an immunocompetent healthy host. Breast milk contains a variety of immunoactive compounds, including immune cells, antibodies, growth factors, and cytokines supporting the newborn’s immature immune system. To characterize the impact of HCMV reactivation on breast milk cytokines, we analyzed longitudinal breast milk samples of four IgG-seropositive and three IgG-seronegative mothers of preterm infants using Proximity Extension Assay (PEA) technology (Olink Proteomics, Uppsala, Sweden). Cytokine profiling revealed elevated cytokine levels in IgG-seropositive mothers’ milk whey. Reactivating mothers showed higher levels of CC-chemokines (MCP-2, CCL19, and CCL20) and CXC-chemokines (IL-8, CXCL9, CXCL10, and CXCL11), such as the proinflammatory cytokine IL-17C, glycoprotein CD5, and TNFSF14. HCMV reactivation seems to influence the cytokine profile in human breast milk. This work could open the door for further studies analyzing distinct relations of the cytokine network as well as phenotypical and functional T cell properties in background of HCMV DNA dynamics in early lactation.

2021 ◽  
Vol 5 (1SP) ◽  
pp. 21
Author(s):  
Zakiudin Munasir

ABSTRACT Background: After birth, preterm infants face numerous challenges, including short and long-term morbidities, to survive and grow well with impaired immune and gastrointestinal systems. According to data from 184 countries, preterm birth rate ranges from 5-18%, accounting for 35% of all new born deaths. Purpose: This literature review aimed to summarize the evidence for the impact of prematurity on immune system development and the benefit of prebiotics on gut microbiota and immune responses. Discussion: Various studies in this narrative literature review showed that preterm infants have both qualitative and quantitative immune response deficits compared to term infants. Preterm newborns also have impaired intestinal immunity, underdeveloped intestinal mucosa barrier, and gut dysbiosis, which predisposes them to life-threatening infections. Early balanced gut microbiota in infants believed to be essential for adequate intestinal physiological functions and immune system maturation. The use of prebiotics, including human milk oligosaccharides (HMOs) in human breast milk, has been found to decrease the risk of various infections and cognitive impairment. A previous study found that prebiotic oligosaccharides supplementation was well-tolerated, significantly increased Bifidobacteria growth, and reduced the presence of gut pathogens. Conclusions: There was robust evidence that breast milk and prebiotics supplementation may support the gut microbiome and immune system in preterm infants. However, different types of synthetic prebiotics offer different benefits, and the protective effect seems to depend on the supplementation duration and dosage.


2016 ◽  
Vol 310 (7) ◽  
pp. R578-R585 ◽  
Author(s):  
Alex Man Lai Wu ◽  
Liana Dedina ◽  
Pooja Dalvi ◽  
Mingdong Yang ◽  
John Leon-Cheon ◽  
...  

While it is well recognized that riboflavin accumulates in breast milk as an essential vitamin for neonates, transport mechanisms for its milk excretion are not well characterized. The multidrug efflux transporter ABCG2 in the apical membrane of milk-producing mammary epithelial cells (MECs) is involved with riboflavin excretion. However, it is not clear whether MECs possess other riboflavin transport systems, which may facilitate its basolateral uptake into MECs. We report here that transcripts encoding the second ( SLC52A2) and third ( SLC52A3) member of the recently discovered family of SLC52A riboflavin uptake transporters are expressed in milk fat globules from human breast milk. Furthermore, Slc52a2 and Slc52a3 mRNA are upregulated in the mouse mammary gland during lactation. Importantly, the induction of Slc52a2, which was the major Slc52a riboflavin transporter in the lactating mammary gland, was also observed at the protein level. Subcellular localization studies showed that green fluorescent protein-tagged mouse SLC52A2 mainly localized to the cell membrane, with no preferential distribution to the apical or basolateral membrane in polarized kidney MDCK cells. These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk.


2018 ◽  
Vol 9 (3) ◽  
pp. 1747-1754 ◽  
Author(s):  
Liang Jie ◽  
Ce Qi ◽  
Jin Sun ◽  
Renqiang Yu ◽  
Xiangyu Wang ◽  
...  

The main BCFAs in preterm breast milk were iso-14:0, iso-15:0, anteiso-15:0, iso-16:0, iso-17:0, and anteiso-17:0, which were low than that in term breast milk. They were mainly located in the sn-2 position of TAGs and concentration in colostrum.


Glycobiology ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 774-786 ◽  
Author(s):  
Sara Porfirio ◽  
Stephanie Archer-Hartmann ◽  
G Brett Moreau ◽  
Girija Ramakrishnan ◽  
Rashidul Haque ◽  
...  

Abstract Human breast milk is an incredibly rich and complex biofluid composed of proteins, lipids and complex carbohydrates, including a diverse repertoire of free human milk oligosaccharides (HMOs). Strikingly, HMOs are not digested by the infant but function as prebiotics for bacterial strains associated with numerous benefits. Considering the broad variety of beneficial effects of HMOs, and the vast number of factors that affect breast milk composition, the analysis of HMO diversity and complexity is of utmost relevance. Using human milk samples from a cohort of Bangladeshi mothers participating in a study on malnutrition and stunting in children, we have characterized breast milk oligosaccharide composition by means of permethylation followed by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS) analysis. This approach identified over 100 different glycoforms and showed a wide diversity of milk composition, with a predominance of fucosylated and sialylated HMOs over nonmodified HMOs. We observed that these samples contain on average 80 HMOs, with the highest permethylated masses detected being >5000 mass units. Here we report an easily implemented method developed for the separation, characterization and relative quantitation of large arrays of HMOs, including higher molecular weight sialylated HMOs. Our ultimate goal is to create a simple, high-throughput method, which can be used for full characterization of sialylated and/or fucosylated HMOs. These results demonstrate how current analytical techniques can be applied to characterize human milk composition, providing new tools to help the scientific community shed new light on the impact of HMOs during infant development.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1039 ◽  
Author(s):  
Katríona E. Lyons ◽  
C. Anthony Ryan ◽  
Eugene M. Dempsey ◽  
R. Paul Ross ◽  
Catherine Stanton

Human breast milk is considered the optimum feeding regime for newborn infants due to its ability to provide complete nutrition and many bioactive health factors. Breast feeding is associated with improved infant health and immune development, less incidences of gastrointestinal disease and lower mortality rates than formula fed infants. As well as providing fundamental nutrients to the growing infant, breast milk is a source of commensal bacteria which further enhance infant health by preventing pathogen adhesion and promoting gut colonisation of beneficial microbes. While breast milk was initially considered a sterile fluid and microbes isolated were considered contaminants, it is now widely accepted that breast milk is home to its own unique microbiome. The origins of bacteria in breast milk have been subject to much debate, however, the possibility of an entero-mammary pathway allowing for transfer of microbes from maternal gut to the mammary gland is one potential pathway. Human milk derived strains can be regarded as potential probiotics; therefore, many studies have focused on isolating strains from milk for subsequent use in infant health and nutrition markets. This review aims to discuss mammary gland development in preparation for lactation as well as explore the microbial composition and origins of the human milk microbiota with a focus on probiotic development.


2018 ◽  
Vol 87 (1) ◽  
Author(s):  
Jimin Kim ◽  
Yong-Jae Kim ◽  
Jae Wha Kim

ABSTRACT Sialyllactose (SL) is a representative human milk oligosaccharide (HMO) of human breast milk. The roles of SL in infant brain development and immunity have been reported in previous studies. In this study, we identified the impact of SL on innate immunity. Our results showed that the administration of SL had significant efficacy on bacterial clearance in Pseudomonas aeruginosa K-infected mice. We also examined the role of SL in the human THP-1 macrophage-like cell line. SL effectively promoted receptor-mediated endocytosis and phagocytosis. Furthermore, SL accelerated the recruitment of Rac1 to the cell membrane, leading to the generation of reactive oxygen species for the elimination of phagocytosed bacteria. Our findings provide a new perspective on the role of SL in breast milk and suggest its application as a therapeutic agent to treat bacterial and viral infections.


1996 ◽  
Vol 40 (3) ◽  
pp. 201-204 ◽  
Author(s):  
Hideomi Asanuma ◽  
Kei Numazaki ◽  
Nobuo Nagata ◽  
Tomoyuki Hotsubo ◽  
Kiyotaka Horino ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 338 ◽  
Author(s):  
Katrin Lazar ◽  
Tabea Rabe ◽  
Rangmar Goelz ◽  
Klaus Hamprecht

Human cytomegalovirus (HCMV) is shed into breast milk in nearly every seropositive woman during lactation. This reactivation shows mostly a self-limited, unimodal course. The dynamics and functional role of HCMV-specific-IgG in breast milk and in plasma during reactivation are unknown. Milk whey viral loads were monitored with real-time PCR in 18 HCMV-seropositive mothers over two months postpartum. HCMV-antibody binding assays (ECLIA) and antigen-specific immunoblotting were performed from plasma and corresponding milk samples. Epithelial-cell-specific neutralization was used to analyze functional antibodies in plasma- and whey-pools. Viral loads in milk whey showed unimodal courses in 15 of 18 mothers with peak viral loads around one month postpartum. HCMV-specific-IgG-antibodies increased significantly in plasma and milk whey during reactivation. The mean levels of plasma IgG were about 275-fold higher than in whey. Only antibodies against tegument protein p150 were continuously expressed in both compartments. Anti-glycoprotein-B1 IgG-antibodies were variably expressed in whey, but continuously in plasma. Neutralization assays showed 40-fold higher NT-50 values in plasma compared to whey at two months postpartum. During reactivation, HCMV-specific-IgG reactivities and neutralizing capacities are much lower in whey than in plasma. Therefore, their specific role in the decrease and discontinuation of virus-shedding in milk remains unclear.


2021 ◽  
Author(s):  
Santosh Lamichhane ◽  
Heli Siljander ◽  
Daniel Duberg ◽  
Jarno Honkanen ◽  
Suvi M. Virtanen ◽  
...  

AbstractBackgroundChemical composition of human breast milk is highly variable inter- and intra-individually. Environmental factors are suspected to partly explain the compositional variation, however, their impact on breast milk composition is currently poorly understood.ObjectivesWe sought (1) to define the impact of maternal exposure to per- and polyfluoroalkyl substances (PFAS) on lipid composition of human breast milk, and (2) to study the combined impact of maternal PFAS exposure and breast milk lipid composition on the growth of the infants.MethodsIn a mother-infant study (n=44) we measured the levels of PFAS and lipids in maternal serum and conducted lipidomics analysis of breast milk at birth and at 3 months of infant age, by using ultra high performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry. Maternal diet was studied by a validated food frequency questionnaire.ResultsPFAS levels were inversely associated with total lipid levels in the breast milk collected at birth. In the high exposure group, the ratio of acylated saturated and polyunsaturated fatty acids in triacylglycerols was increased. Moreover, high exposure to PFAS associated with the altered phospholipid composition, which was indicative of unfavorable increase in the size of milk fat globules. These changes in the milk lipid composition were further associated with slower infant growth and with elevated intestinal inflammatory markers.DiscussionOur data suggest that the maternal exposure to PFAS impacts the nutritional quality of the breast milk, which, in turn, may have detrimental impact on the health and growth of the children later in life.


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