The Human Microbiome and Its Potential Importance to Pediatrics

Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
PEDIATRICS (Impact Factor: 5.47). 04/2012; 129(5):950-60. DOI: 10.1542/peds.2011-2736
Source: PubMed


The human body is home to more than 1 trillion microbes, with the gastrointestinal tract alone harboring a diverse array of commensal microbes that are believed to contribute to host nutrition, developmental regulation of intestinal angiogenesis, protection from pathogens, and development of the immune response. Recent advances in genome sequencing technologies and metagenomic analysis are providing a broader understanding of these resident microbes and highlighting differences between healthy and disease states. The aim of this review is to provide a detailed summary of current pediatric microbiome studies in the literature, in addition to highlighting recent findings and advancements in studies of the adult microbiome. This review also seeks to elucidate the development of, and factors that could lead to changes in, the composition and function of the human microbiome.

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    • "This is further supported by studies associating dysbiosis in early life with immune-mediated childhood disorders [38] [39] [40] and obesity [41] [42]. Dysbioses can arise from common pediatric practices, including preterm delivery, formula feeding, cesarean section, and use of antibiotics [42] [43] (Fig. 1). Interestingly, cesarean section [43] and antibiotic use [44] are independently associated with an increased susceptibility to immune-mediated disease, potentially through dysregulation of host immune homeostasis [44] [45]. "
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    ABSTRACT: The early postnatal period is a critical window for intestinal and immune maturation. Intestinal development and microbiome diversity and composition differ between breast- (BF) and formula-fed (FF) infants. Mechanistic examination into host–microbe relationships in healthy infants has been hindered by ethical constraints surrounding tissue biopsies. Thus, a statistically rigorous analytical framework to simultaneously examine both host and microbial responses to dietary/environmental factors using exfoliated intestinal epithelial cells was developed. Differential expression of ∼1200 genes, including genes regulating intestinal proliferation, differentiation and barrier function, was observed between BF and FF term infants. Canonical correlation analysis uncovered a relationship between microbiome virulence genes and host immunity and defense genes. Lastly, exfoliated cells from preterm and term infants were compared. Pathways associated with immune cell function and inflammation were up-regulated in preterm, whereas cell growth-related genes were up-regulated in the term infants. Thus, coordinate measurement of the transcriptomes of exfoliated epithelial cells and microbiome allows inquiry into mutualistic host–microbe interactions in the infant, which can be used to prospectively study gut development or, retrospectively, to identify potential triggers of disease in banked samples.
    FEBS Letters 11/2014; 588(22). DOI:10.1016/j.febslet.2014.07.008 · 3.17 Impact Factor
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    • "Some data also indicate that maternal antibiotic intake in pregnancy influences the gut microbiota in the offspring, [11] and that perturbations caused by antibiotics in the infant [12] and adult microbiota [13,14] may persist for several years. Antibiotics are in fact one of the main environmental stressors that lead to the replacement of symbiotic bacteria by otherwise under-represented potentially pathogenic bacteria [13,15]. "
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    ABSTRACT: The infant microbiota may play a pathogenic role in coeliac disease (CD). Antibiotic treatment in pregnancy is common and could significantly impact the infant microbiota. In this study, we aimed to investigate the association between antibiotic exposure during pregnancy and CD in offspring. Prospective questionnaire data on antibiotic exposure in pregnancy were available in 8729 children participating in the All Babies in Southeast Sweden (ABIS) cohort study, and of these 46 developed CD until December 2006. Cox regression estimated hazard ratios (HRs) for CD in the offspring among mothers exposed to antibiotics during pregnancy, with adjustment for parent-reported diary data on breastfeeding, age at gluten introduction and number of infections in the child's first year of life. Of the 1836 children exposed to antibiotics during pregnancy, 12 (0.7%) children developed CD as compared with 34/6893 (0.5%) unexposed children (HR = 1.33; 95%CI = 0.69-2.56). Risk estimates remained unchanged after adjustment for breastfeeding, age at gluten introduction and infection load in the child's first year of life (HR = 1.28; 95%CI = 0.66-2.48). We found no statistically significant association between antibiotic exposure during pregnancy and CD in offspring. This lack of association may either be true or the result of limited statistical power.
    BMC Gastroenterology 04/2014; 14(1):75. DOI:10.1186/1471-230X-14-75 · 2.37 Impact Factor
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    • "While in infants, the phylogenetic structure of the enterocyte-associated GM fraction generally resembled the one observed in the fecal microbiota, in adults it showed a totally different structure, being enriched in Bacteroides-Prevotella and Enterobacteriaceae and depleted in Clostridium clusters IV and XIVa. This observation suggests that the GM of breast-fed infants is selected for a closer interaction with the host enterocytes, a factor that may be important for the establishment of the intense cross-talk with the host immune system which drives the process of immune education [51]. In fact, enriched in Bifidobacterium and Enterobacteriaceae, the infant-type enterocyte-associated microbiota fraction is specifically structured to drive immune education in early infancy [52]. "
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    ABSTRACT: Co-evolved as an integral component of our immune system, the gut microbiota provides specific immunological services at different ages, supporting the immune education during our infancy and sustaining a well-balanced immunological homeostasis during the course of our life. In order to figure out whether this involves differences in the microbial groups primarily interacting with the host immune system, we developed a non-invasive HT29 cell-based minimal model to fingerprint the enterocyte-associated microbiota fraction in infants and adults. After depicting the fecal microbial community of 12 breast-fed infants and 6 adults by 16S rDNA amplicon pools 454 pyrosequencing, their respective HT29 cell-associated gut microbiota fractions were characterized by the universal phylogenetic array platform HTF-Microbi.Array, both in the presence and absence of a tumor necrosis factor-alpha (TNF-α)-mediated pro-inflammatory stimulus. Our data revealed remarkable differences between the enterocyte-associated microbiota fractions in breast-fed infants and adults, being dominated by Bifidobacterium and Enterobacteriaceae the first and Bacteroides-Prevotella and Clostridium clusters IV and XIVa the second. While in adults TNF-α resulted in a profound impairment of the structure of the enterocyte-associated microbiota fraction, in infants it remained unaffected. Differently from the adult-type gut microbial community, the infant-type microbiota is structured to cope with inflammation, being co-evolved to prime the early immune response by means of transient inflammatory signals from gut microorganisms.
    PLoS ONE 11/2013; 8(11):e81762. DOI:10.1371/journal.pone.0081762 · 3.23 Impact Factor
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