The upper respiratory tract is the natural niche for

The upper respiratory tract is the natural niche for respiratory bacterial and viral pathogens and the origin for consecutive respiratory tract infections (RTI). Potential pathogenic bacteria are embedded in a glucagon receptor of commensals, jointly forming the nasopharyngeal microbiota. Microbial colonization succession is highly influenced by environmental factors, host factors, and bacterial acquisition during the first years of life (Koppen et al., 2015). Recently, we published a first crude picture of microbiota development in children over the first two years of life (Biesbroek et al., 2014b). Despite large sampling intervals, the composition of the nasopharyngeal microbiota appeared highly dynamic, especially in the first six months of life. As we hypothesized that a balanced microbiota is more resilient to bacterial acquisition and overgrowth, we focused on the stability of the microbial profiles. Intriguingly, early microbiota composition (six weeks of life) predicted microbiota stability over the first two years of life: stable profiles were associated with (exclusive) breastfeeding and fewer respiratory tract infections in the consecutive period (Biesbroek et al., 2014a, 2014b). These findings indicate that there is a window of opportunity during early life where a stable microbial signature is formed, that is associated with protection against respiratory symptoms. These data are supported by both epidemiological (Vissing et al., 2013) and murine (Gollwitzer et al., 2014) data. Although timing and order of exposure to specific groups of microbes, like mediated by mode of delivery, may have crucial consequences on development of the microbial profile, studies investigating the respiratory microbiota of healthy young children in detail in a longitudinal fashion are lacking.
Materials and Methods
Results
Discussion
Conclusion In conclusion, the respiratory microbiota in neonatal life develops from an initially maternally or environmentally transmitted mixed flora via S. viridans to S. aureus dominance, followed by differentiation into one of several niche-specific microbiota profiles after one week of age. Mode of delivery affected early respiratory microbiota development significantly, especially the timing of seeding and the abundance of potentially protective commensals. These effects on early microbiota development may be an important clue for the role of the microbiota in respiratory health later in life, which therefore deserves further investigation.
Author Contributions
Funding This work was supported by the Spaarne Gasthuis Hoofddorp and University Medical Center Utrecht, the Dutch Organization for Scientific Research through NWO-Vidi grant (91715359), and Top consortia for Knowledge and Innovation, Agri & Food (TKI-AF-12190). The funding sources had no role in the design, execution, analyses, or interpretation of the data of this study.
Conflict of Interest
Acknowledgments
Introduction Given the long-term survival in pediatric liver transplantation (LT), maintaining stable liver function and preserving allograft histology are paramount. Protocol biopsies (PBs) from LT recipient children revealed frequent allograft inflammation and fibrosis (Evans et al., 2006; Scheenstra et al., 2009; Hubscher, 2011; Venturi et al., 2012, 2014; Gurevich et al., 2015), in stable LT recipients without predisposing factors (Evans et al., 2006; Venturi et al., 2014; Gurevich et al., 2015; Miyagawa-Hayashino et al., 2012). The etiopathogenesis of these “idiopathic” changes is unknown, while graft age, subclinical rejection and medication non-compliance have been considered as possible aetiologies (Hubscher, 2011; Venturi et al., 2014; Miyagawa-Hayashino et al., 2012). Among these, the donor specific class II HLA antibodies have been shown to play an important role in the allograft evolution. This proposition of antibody mediated subclinical inflammation gains more emphasis as the C4d deposition in the hepatic tissue has been shown to correlate with the antibody presence (Miyagawa-Hayashino et al., 2012; Kozlowski et al., 2011; Salah et al., 2014). While continuity between uncontrolled inflammation and hepatic fibrosis was documented in hepatitis C and auto-immune hepatitis (AIH), this was not the case for pediatric LT recipients. To establish a temporal association between inflammation and fibrosis, sequential PBs need to be evaluated to verify if inflammation precedes fibrosis histologically. This has not been done in the context of pediatric LT where all the studies have evaluated biopsies cross-sectionally wherein co-existing inflammation and fibrosis could be evaluated but not sequential development (Evans et al., 2006; Scheenstra et al., 2009). Hence the conflictory evidence of inflammation not resulting in fibrosis in pediatric LT versus other inflammatory hepatic diseases. In AIH, the HLA-DRB1*03/04 allele is considered an independent predictor of portal fibrosis (Montano-Loza et al., 2006; de Boer et al., 2014; Liberal et al., 2015). As AIH is the prototype of immune dysregulation-mediated hepatic disease, examining its role in LT recipients is the next logical step: we sought to evaluate “idiopathic” allograft changes by analysing serial PBs in a complication-free LT recipient cohort.