Project description:91 preterm infant gut metaproteomes measured in technical duplicate using an eleven salt pulse 2D-LC-MS/MS method. Samples represent 17 preterm infants over the first several weeks of life, of which 6 preterm infants eventually developed necrotizing enterocolitis.
Project description:Incidence of obesity is increasingly prevalent among children: global pediatric obesity incidence raised by 30% globally in the last two decades and increased tenfold in the last four decades. Being obese as a child increases the likelihood of being obese as an adult, and suffer from obesity-related health complications. Adipose tissue development in the first year of life may determine adiposity in early childhood. Our aim is to understand mechanisms that control healthy adipose tissue development from infancy to childhood. We collected adipose tissue specimens during elective surgery from the inguinal region of human infants and children, with normal BMI and without known metabolic or endocrine diseases. Samples were proceesed for extraction of total RNA, using phenol:chlorophorm extraction. Next generation RNA sequencing were performed.
Project description:Infants and young children are more susceptible to common respiratory pathogens compared to adults, but can fare better against novel pathogens like SARS-CoV-2. The mechanisms by which infants and young children mount effective responses to respiratory pathogens are unknown. Here, we demonstrate through study of lungs and lung-associated lymph nodes (LLN) from infant and pediatric organ donors, aged 0-13 years, that bronchus-associated lymphoid tissue (BALT), develops in lungs during the first year of life. BALT structures, consisting of B cell follicles and T cell zones, increase in numbers in the early years, and subsequently decrease over childhood coincident with accumulation of memory T cells in the lung. Early life BALT contains germinal centers and supports B cell differentiation, clonal expansion, somatic hypermutation, and immunoglobulin class switching. High dimensional flow cytometry reveals seeding of lungs by newly formed B cells (transitional cells) during infancy coincident with the timing of maximal BALT formation. We further demonstrate increased lung-localized B cell responses during respiratory virus infection in infants. Together, our findings provide novel evidence for BALT as an early life adaptation for mobilizing in situ immune protection to the diverse respiratory challenges during this formative life stage.
Project description:The prevalence of atopic diseases has increased with atopic dermatitis (AD) as the earliest manifestation. We assessed if molecular risk factors in atopic mothers influence their offsprings’ susceptibility to an atopic disease. Pairs of pregnant women and their infants with or without parental atopy were followed over the first 2 years of life. Global DNA methylation and differentially methylated regions (DMR) were determined in atopic and non-atopic mothers. During the first 2 years of life, AD was more prevalent in children of atopic compared to non-atopic mothers with an increase in food sensitization in children with AD. 165 DMRs distinguished atopic from non-atopic mothers. Maternal atopy combined with DMRs increased the offsprings’ predicted risk to develop AD from an odds ratio of 2.56 to 4.26.
Project description:Colonizing commensal bacteria after birth are required for the proper development of the gastrointestinal tract. It is believed that bacterial colonization pattern in neonatal gut affects gut barrier function and immune system maturation. Studies on the development of faecal flora microbiota in infants on various formula feeds showed that the neonatal gut was first colonized with enterococci followed by other flora microbiota such as Bifidobacterium in breast feeding infants. Intriguingly, Bjorksten group Other studies showed that Bbabies who developed allergy were less often colonized with Enterococcus during the first month of life as compared to healthy infants. A lot of Many studies have been done on conducted to elucidate how bifidobacteria or lactobacilli, some of which are considered probiotic, regulate infant gut immunity. However, much fewer studies have been focused on enterococi. In our study, we demonstrate that E. faecalis, isolated from healthy newborns, suppress inflammatory responses activated in vivo and in vitro. We found E. faecalis attenuates proinflammatory cytokine secretions, especially IL-8, through JNK and p38 signaling pathways. This finding shed light on how the first colonizer, E.faecalis, regulate inflammatory responses in the host. Samples are analysed using web-based GEArray Expression Analysis Suite
Project description:This is the first report characterizing noncoding RNA expression in a congenital heart defect. The striking shift in expression of noncoding RNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing and translation of developmentally important genes and possibly contributing to the cardiac defect. The importance of noncoding RNAs (ncRNA), especially microRNAs, for maintaining stability in the developing vertebrate heart has recently become apparent. However, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants. We found 61 microRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a remarkable resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of microRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 microRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and two spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of the critical cardiac developmental genes. Taken together, these observations suggest a link between snoRNA level in the myocardium, spliceosomal function and heart development. We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants
Project description:Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention. Longitudinal study including 15 samples
Project description:Tolerance to dietary antigens is critical to avoid deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens is poorly understood. Here we demonstrate that the goblet cell-derived resistin-like molecule beta (RELMb) is a critical regulator of oral tolerance. We find that RELMb is abundant in serum in both food allergic patients and mouse models of FA. Deletion of RELMβ protects mice from FA, development of food antigen specific IgE and anaphylaxis. RELMb disrupts food tolerance through modulation of the gut microbiome by suppressing gut Lactobacilli. Tolerance is maintained via local production of indole derivatives driving FA protective RORgt+ regulatory T (Treg) cells via activation of the aryl hydrocarbon receptor (AhR). RELMb antagonism in the peri-weaning period restored oral tolerance and protected genetically prone offspring from developing FA later in life. Together, our data identify RELMb as mediating both a novel gut immune-epithelial circuit regulating tolerance to food antigens, a new mode of innate control of antigen specific adaptive immunity via microbiome editing and targetable candidates in this circuit for prevention and treatment of FA.
Project description:The objective of the present study was to identify the nutrient utilization and the SCFA production potential of gut microbes during the first year of life. The 16S sequencing data represents 100 mother-child pairs, longitudinally for the infants (0, 3mo, 6mo and 12mo) and mothers 18 weeks pregnancy. We wanted to identify the SCFA composition in pregnant woman and their infants through the first year of life, and their correlation to gut bacteria and other influencal factors. Metaproteomics on selected infants were analyzed to look for nutrient sources used by potential SCFA producers.