Ontology highlight
ABSTRACT:
PROVIDER: PRJNA706659 | ENA |
REPOSITORIES: ENA
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Project description:Human breast milk contains a diverse community of bacteria but factors that produce variation in the breast milk microbiome are largely unknown. We evaluated if 1) maternal factors including breastfeeding practices modified the diversity and abundance of bacterial communities in breast milk and 2) if subclinical mastitis (SCM), an asymptomatic inflammatory condition occurring during lactation, induced a distinctive microbiota signature.
| EGAS00001003044 | EGA
Project description:Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic E. coli, Shigella spp., Salmonella enterica serovar Typhi, Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for Shigella and diarrheagenic E. coli antigens, although sets of S. aureus, S. pneumoniae, and some M. tuberculosis antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants.
2020-12-28 | GSE163901 | GEO
Project description:Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic E. coli, Shigella spp., Salmonella enterica serovar Typhi, Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for Shigella and diarrheagenic E. coli antigens, although sets of S. aureus, S. pneumoniae, and some M. tuberculosis antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants.
2020-12-28 | GSE163902 | GEO
Project description:Milk, renowned for its nutritional value, harbours bioactive compounds, including lactoferrin (Lf) [1], immunoglobulins, and functional proteins suggesting broader functionalities beyond nutrition. Lf, an iron glycoprotein, exhibits antimicrobial properties against bacteria, fungi, and viruses."In"this st"dy, Immune Powder (a functional dairy formulation) and Fractionated Milk Protein (FMP; a blend of bioactive proteins isolated from skim milk) containing Lf, zinc, and immunoglobulins produced by Ausnutria Australia Dairy Pty Ltd were evaluated for their broad spectrum pharmacological activity. In particular, the study aims to investigate the antibacterial (against pathogenic Escherichia coli), prebiotic (promoting Lactobacillus delbrueckii growth), anti-inflammatory (against RAW264.7 macrophages), and antiviral (against human coronavirus 229E, HCoV-229E cultured on MCR-5 cells) effects of the formulations. In addition, the impact of simulated gastric digestion on the efficacy of the formulations was explored. LCMS-based proteomics analysis was implemented to unveil cellular and molecular mechanisms underlying antiviral activity. The Immune Powder demonstrated antibacterial activity against E. coli (up to 99.74 ± 11.47% inhibition at 62.5 mg/mL), coupled with prebiotic action (10.84 ± 2.2 viability fold change at 125 mg/mL), albeit diminished post-digestion (p <0.01). The Immune Powder effectively mitigated inflammation by reducing NO production, with efficacy declining post-digestion (p < 0.0001). The potential antiviral activity of Immune Powder against HCoV-229E also shown an increase of 2.62 ± 0.42 in cell viability when treated at 500 µg/mL. Similarly, FMP exhibited antibacterial potency pre-digestion at high concentration (95.56 ± 1.23% inhibition at 125 mg/mL), and post-digestion at lower doses (61.82 ± 5.58% inhibition at 3906.25 µg/mL). FMP also shown enhanced prebiotic activity post-digestion (p < 0.0001), anti-inflammation pre-digestion, and significant antiviral activity against HCoV-229E (1.72 ± 0.52 cell viability fold change). The proteomics study suggested both formulas shared similar antiviral mechanism by inhibiting scavenger receptor binding and ECM interaction.
2024-12-02 | PXD052339 | Pride
Project description:Background: Human milk extracellular vesicles (EVs) affect various cell types in the gastrointestinal tract, including T cells, and play a role in the development of the newborn’s immune system by delivering specific molecular cargo to target cells. Although maternal allergic sensitization alters the composition of milk, it is unknown whether this impacts the function of milk EVs. Therefore, we analyzed the T cell modulatory capacity and compared the protein and miRNA cargo of EVs from milk of allergic and non-allergic mothers. Methods: EVs were isolated from human milk from allergic and non-allergic donors by differential centrifugation, density gradient floatation and size exclusion chromatography. Functional modulation of primary human CD4+ T cells by EVs was assessed in vitro. Proteomic analysis and small RNA sequencing was performed on milk EVs to evaluate protein and miRNA abundance and to identify cellular targets of this EV cargo in relevant T cell signaling pathways. Results: T cell proliferation, activation and cytokine production were suppressed in the presence of milk EVs. Remarkably, milk EVs from allergic mothers modulated T cell activation to a lesser extent than EVs from non-allergic mothers. Integrative multi-omics analysis identified EV cargo of which the cellular targets could be linked to T cell activation-associated processes. Conclusions: Milk EVs from non-allergic mothers are stronger inhibitors of T cell activation compared to milk EVs from allergic mothers. This altered functionality might be linked to small changes in modulation of certain T cell signaling pathways.
2022-10-30 | GSE216498 | GEO
Project description:Background—Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in older individuals. Currently, therapeutic options are limited to surgical interventions. Although it has long been known that AAA tissue is enriched in B cells and immunoglobulins, their involvement in AAA pathogenesis remains controversial. Methods and Results— We investigated the role of B cells and immunoglobulins in a murine model of AAA, induced with a periaortic application of CaCl2, and in human AAA. Both human and mouse AAA tissue showed B cell infiltration. Mouse AAA tissue showed deposition of IgG and activation of Syk, a key molecule in B cell activation and immunoglobulin function, which were localized to infiltrating cells including B cells and macrophages. B cell-deficient muMT mice showed suppression of AAA development that was associated with reduced activation of Syk and less expression of Mmp9. Administration of exogenous immunoglobulins restored the blunted Syk activation and AAA development in muMT mice. Additionally, exogenous immunoglobulins induced IL-6 and MMP9 secretions in human AAA tissue cultures. Furthermore, administration of R788, a specific Syk inhibitor, suppressed AAA expansion, reduced inflammatory response, and reduced immunoglobulin deposition in AAA tissue. Conclusions—From these results, we concluded that B cells and immunoglobulins participated in AAA pathogenesis by promoting inflammatory and tissue destructive activities. Finally, we identified Syk as a potential therapeutic target.
2018-04-25 | GSE109639 | GEO
Project description:Background—Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in older individuals. Currently, therapeutic options are limited to surgical interventions. Although it has long been known that AAA tissue is enriched in B cells and immunoglobulins, their involvement in AAA pathogenesis remains controversial. Methods and Results— We investigated the role of B cells and immunoglobulins in a murine model of AAA, induced with a periaortic application of CaCl2, and in human AAA. Both human and mouse AAA tissue showed B cell infiltration. Mouse AAA tissue showed deposition of IgG and activation of Syk, a key molecule in B cell activation and immunoglobulin function, which were localized to infiltrating cells including B cells and macrophages. B cell-deficient muMT mice showed suppression of AAA development that was associated with reduced activation of Syk and less expression of Mmp9. Administration of exogenous immunoglobulins restored the blunted Syk activation and AAA development in muMT mice. Additionally, exogenous immunoglobulins induced IL-6 and MMP9 secretions in human AAA tissue cultures. Furthermore, administration of R788, a specific Syk inhibitor, suppressed AAA expansion, reduced inflammatory response, and reduced immunoglobulin deposition in AAA tissue. Conclusions—From these results, we concluded that B cells and immunoglobulins participated in AAA pathogenesis by promoting inflammatory and tissue destructive activities. Finally, we identified Syk as a potential therapeutic target.
2018-04-25 | GSE109638 | GEO
Project description:Breastfeeding is vital for reducing morbidity and mortality, yet exclusive breastfeeding rates are low, with insufficient milk supply being a major weaning factor whose molecular causes remain largely unknown. In this study, we collected fresh milk samples from 30 lactating individuals, classified as low, normal, or high milk producers at multiple postpartum stages, and conducted extensive genomic and microbiome analysis. Using bulk RNA sequencing on human milk fat globules (MFG), milk cells, and breast tissue, we found that MFG-derived RNA closely resembles RNA from milk luminal cells. Furthermore, bulk and single-cell RNA-seq revealed changes in the transcriptome and cellular content linked to milk production. We identified specific genes and cell-type proportions differing in low and high milk production. Infant microbiome diversity was affected by feeding type, but not by maternal milk supply. This study provides a comprehensive human milk transcriptomic catalog, identifies genes associated with milk production, and highlights MFG as a useful biomarker for milk transcriptome analysis.
2024-11-30 | GSE275627 | GEO
Project description:Breastfeeding is vital for reducing morbidity and mortality, yet exclusive breastfeeding rates are low, with insufficient milk supply being a major weaning factor whose molecular causes remain largely unknown. In this study, we collected fresh milk samples from 30 lactating individuals, classified as low, normal, or high milk producers at multiple postpartum stages, and conducted extensive genomic and microbiome analysis. Using bulk RNA sequencing on human milk fat globules (MFG), milk cells, and breast tissue, we found that MFG-derived RNA closely resembles RNA from milk luminal cells. Furthermore, bulk and single-cell RNA-seq revealed changes in the transcriptome and cellular content linked to milk production. We identified specific genes and cell-type proportions differing in low and high milk production. Infant microbiome diversity was affected by feeding type, but not by maternal milk supply. This study provides a comprehensive human milk transcriptomic catalog, identifies genes associated with milk production, and highlights MFG as a useful biomarker for milk transcriptome analysis.
2024-11-30 | GSE275626 | GEO