Early-life environment, developmental immunotoxicology, and the risk of pediatric allergic disease including asthma

Author(s):  
Rodney R. Dietert ◽  
Judith T. Zelikoff
2015 ◽  
Vol 35 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Ganesa Wegienka ◽  
Edward Zoratti ◽  
Christine Cole Johnson

2011 ◽  
Vol 140 (5) ◽  
pp. 835-841 ◽  
Author(s):  
L. H. MORTENSEN ◽  
A. B. MAIER ◽  
P. E. SLAGBOM ◽  
G. PAWELEC ◽  
E. DERHOVANESSIAN ◽  
...  

SUMMARYHuman cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73–94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42%vs. partners: 51%,P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90%vs. DZ: 88%,P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection – even under continuous within-partnership exposure – appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.


2017 ◽  
Vol 8 (5) ◽  
pp. 513-519 ◽  
Author(s):  
T. Bianco-Miotto ◽  
J. M. Craig ◽  
Y. P. Gasser ◽  
S. J. van Dijk ◽  
S. E. Ozanne

Developmental origins of health and disease (DOHaD) is the study of how the early life environment can impact the risk of chronic diseases from childhood to adulthood and the mechanisms involved. Epigenetic modifications such as DNA methylation, histone modifications and non-coding RNAs are involved in mediating how early life environment impacts later health. This review is a summary of the Epigenetics and DOHaD workshop held at the 2016 DOHaD Society of Australia and New Zealand Conference. Our extensive knowledge of how the early life environment impacts later risk for chronic disease would not have been possible without animal models. In this review we highlight some animal model examples that demonstrate how an adverse early life exposure results in epigenetic and gene expression changes that may contribute to increased risk of chronic disease later in life. Type 2 diabetes and cardiovascular disease are chronic diseases with an increasing incidence due to the increased number of children and adults that are obese. Epigenetic changes such as DNA methylation have been shown to be associated with metabolic health measures and potentially predict future metabolic health status. Although more difficult to elucidate in humans, recent studies suggest that DNA methylation may be one of the epigenetic mechanisms that mediates the effects of early life exposures on later life risk of obesity and obesity related diseases. Finally, we discuss the role of the microbiome and how it is a new player in developmental programming and mediating early life exposures on later risk of chronic disease.


2017 ◽  
Vol 8 (5) ◽  
pp. 681-695 ◽  
Author(s):  
J.S.Y. Low ◽  
S.-E. Soh ◽  
Y.K. Lee ◽  
K.Y.C. Kwek ◽  
J.D. Holbrook ◽  
...  

Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease.


2014 ◽  
Vol 109 ◽  
pp. S486
Author(s):  
Abra Guo ◽  
Robin Wilson ◽  
Betsy Stevens ◽  
Caitlin Russell ◽  
Melissa Cohen ◽  
...  

2011 ◽  
Vol 77 (4) ◽  
pp. 626-632 ◽  
Author(s):  
Fritha H. Milne ◽  
Debra S. Judge ◽  
David B. Preen ◽  
Phil Weinstein

Heredity ◽  
2017 ◽  
Vol 118 (6) ◽  
pp. 534-541 ◽  
Author(s):  
L Canario ◽  
N Lundeheim ◽  
P Bijma

Author(s):  
Luba Sominsky ◽  
Adam K. Walker ◽  
Deborah M. Hodgson

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