Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic ...processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention.
ABSTRACT BACKGROUND Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on ...associations between home use of cleaning products and future overweight. METHODS From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants. RESULTS Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio AOR 1.93, 95% confidence interval CI 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score ( p = 0.02) and with increased odds of overweight or obesity ( p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation ( p = 0.2). INTERPRETATION Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3–4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.
Gut microbiota and allergic disease in children Bridgman, Sarah L; Kozyrskyj, Anita L; Scott, James A ...
Annals of allergy, asthma, & immunology,
02/2016, Letnik:
116, Številka:
2
Journal Article
Abstract BACKGROUND Childhood adversity increases risk for cardiovascular disease (CVD) in adulthood. Previously proposed mechanisms suggest the association is mediated by stress reactivity—known to ...be higher in women—and is aggravated by adult stress, but this has not yet been confirmed. Therefore, we investigated sex differences to better understand possible pathways from childhood adversity to CVD. METHODS The National Population Health Survey, a fifteen-year cohort study of Canadians aged 18-49 at baseline was used. Logistics regressions with interaction terms for sex and stressful life events were used to assess the risk of CVD following childhood adversity. In secondary analyses we assessed mediation effects of depression, smoking, alcohol, exercise, and diet using the product of coefficient approach. Mediated moderation was subsequently used to explain sex-moderated effects. RESULTS There was a strong association between childhood adversity and CVD (OR=2.14; 95%CI : 1.56, 2.94) for 3+ childhood adversities). The association was stronger with increasing stressful events, and females with 3+ stressful events exhibited the highest risk of CVD (OR=4.40; 95%CI: 1.98, 9.75). No association was found in men. Depression, smoking, and poor diet partially mediated the relationship between childhood adversity and CVD (14%, 9%, 9% respectively), but differences in these behaviours did not fully explain the sex-specific differences in the mediated moderation analysis. CONCLUSIONS The effect of childhood adverse events on CVD is heightened among women, particularly women with stressful adulthoods, and this difference is not mediated by depression, smoking or poor diet. These findings have important implications for understanding sex differences in CVD risk.
Regulatory bodies worldwide, including Health Canada, have issued warnings about prescribing antidepressants to children and adolescents. We sought to determine whether the Health Canada warning had ...the desired effects on prescribing patterns and outcomes and whether it had any unintended health consequences.
We examined data from prescription and health care databases representing more than 265 000 children, adolescents and young adults annually to determine changes in the rates of antidepressant prescription, use of health services and outcomes in these populations in the 9 years before and the 2 years after the Health Canada warning. We also examined the data for unintended changes in these rates among patients with anxiety disorders. We used young adults as the comparison group because they were not targeted by the warning.
Following the warning, the rate of antidepressant prescriptions decreased among children and adolescents (relative risk RR 0.86, 95% confidence interval CI 0.81-0.91) and among young adults (RR 0.90, 95% CI 0.86-0.93). Ambulatory visits because of depression decreased among children and adolescents (RR 0.90, 95% CI 0.85-0.96) and young adults (RR 0.91, 95% CI 0.87-0.96). The rate of completed suicides among children and adolescents rose significantly after the warning (RR 1.25, 95% CI 1.08-1.44; annual rate per 1000 = 0.04 before and 0.15 after the warning). There was no equivalent change in the rate of completed suicides among young adults (RR 1.01, 95% CI 0.93-1.10; annual rate per 1000 = 0.15 before and 0.22 after the warning). Among patients with an anxiety disorder, the prescription rates did not change among children and adolescents, except for a decrease in the use of selective serotonin reuptake inhibitors other than fluoxetine, but the rates among young adults changed similar to the pattern of changes in the overall prescribing of antidepressants. There was also a significant decrease in the rate of physician visits because of anxiety disorders among young adults after the warning.
Health advisories and warnings issued by regulatory bodies may have unintended consequences on the provision of care, delivery of health services and clinical outcomes. Further efforts are required to ensure that health warnings do not result in unexpected harm.
Background The epithelial cell–derived protein thymic stromal lymphopoietin stimulates dendritic and mast cells to promote proallergic TH 2 responses. Studies of transgenic expression of thymic ...stromal lymphopoietin and its receptor knockout mice have emphasized its critical role in the development of allergic inflammation. Association of genetic variation in thymic stromal lymphopoietin with IgE levels has been reported for human subjects. Objective The aim of this study was to evaluate the relationship between variants of thymic stromal lymphopoietin and asthma and related phenotypes. Methods We selected 6 single nucleotide polymorphisms in thymic stromal lymphopoietin and genotyped 5565 individuals from 4 independent asthma studies and tested for association with asthma, atopy, atopic asthma, and airway hyperresponsiveness by using a general allelic likelihood ratio test. P values were corrected for the effective number of independent single nucleotide polymorphisms and phenotypes. Results The A allele of rs1837253, which is 5.7 kb upstream of the transcription start site of the gene, was associated with protection from asthma, atopic asthma, and airway hyperresponsiveness, with the odds ratios and corrected P values for each being 0.79 and 0.0058; 0.75 and 0.0074; and 0.76 and 0.0094, respectively. Associations between thymic stromal lymphopoietin and asthma-related phenotypes were the most statistically significant observations in our study, which has to date examined 98 candidate genes. Full results are available online at http://genapha.icapture.ubc.ca/. Conclusions A genetic variant in the region of the thymic stromal lymphopoietin gene is associated with the phenotypes of asthma and airway hyperresponsiveness.
Background The innate immune system is essential for host survival because of its ability to recognize invading pathogens and mount defensive responses. Objectives We sought to identify genetic ...associations of innate immunity genes with atopy and asthma and interactions with early viral infections (first 12 months of life) in a high-risk birth cohort. Methods Three Canadian family-based studies and 1 Australian population-based case-control study (n = 5565) were used to investigate associations of 321 single nucleotide polymorphisms (SNPs) in 26 innate immunity genes with atopy, asthma, atopic asthma, and airway hyperresponsiveness. Interactions between innate immunity genes and early viral exposure to 3 common viruses (parainfluenza, respiratory syncytial virus, and picornavirus) were examined in the Canadian Asthma Primary Prevention Study by using both an affected-only family-based transmission disequilibrium test and case-control methods. Results In a joint analysis of all 4 cohorts, IL-1 receptor 2 (IL1R2) and Toll-like receptor 1 (TLR1) SNPs were associated with atopy after correction for multiple comparisons. In addition, an NFKBIA SNP was associated with atopic asthma. Six SNPs (rs1519309 TLR3 , rs740044 ILIR2 , rs4543123 TLR1 , rs5741812 LBP , rs917998 IL18RAP , and rs3136641 NFKBIB ) were significant ( P < .05, confirmed with 30,000 permutations) in both the combined analysis of main genetic effects and SNP-virus interaction analyses in both case-control and family-based methods. The TLR1 variant (rs4543123) was associated with both multiple viruses (respiratory syncytial virus and parainfluenza virus) and multiple phenotypes. Conclusion We have identified novel susceptibility genes for asthma and related traits and interactions between these genes and early-life viral infections.
less than 25% of asthmatic children are well controlled.
to identify factors associated with asthma exacerbation causing emergency department (ED) visits or hospitalizations related to health status, ...socioeconomic status (SES), and drug insurance.
in this retrospective cohort study, complete data were collected on 490 asthmatic children regarding demographics, SES, drug plan characteristics, health status, health resource use, and symptoms. Interview data were linked to administrative data on asthma ED visits and hospitalizations occurring in the following year. Multiple Poisson regression identified independent variables associated with ED visits or hospitalizations in the full cohort and in a subgroup with prescription drug insurance.
younger age, previous emergency visits, nebulizer use, pet ownership, and receipt of asthma education but not an action plan were significantly associated with more frequent exacerbations. In the full cohort, children with high income adequacy had 28% fewer exacerbations than did children with low income adequacy. In the subgroup with drug insurance, girls had 26% fewer exacerbations than did boys, and children with food, drug, or insect allergies had 52% more exacerbations than did children without allergies. Children of families with annual insurance deductibles greater than $90 had 95% fewer exacerbations. Every percentage increase in the proportion of income spent out-of-pocket on asthma medications was associated with a 14% increase in exacerbations.
asthma history, disease management factors, and SES were associated with exacerbations requiring urgent care. In families with drug plans, the magnitude of asthma medication cost-sharing as a proportion of household income, rather than income alone, was significantly associated with exacerbations.
...the net in vivo histone (de)acetylation activity (expressed as the ratio of HDAC/HAT activity) is skewed toward increased histone acetylation in allergic asthmatic subjects, with the intensity of ...increased cellular acetylation activity increasing with BHR severity.
Because it appears that exclusivity of breast-feeding was documented in their study,5 it would be informative for the authors to provide more detailed infant feeding data and present their results ...after stratification by degree of formula supplementation.
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