Lactobacillus casei Abundance Is Associated with Profound Shifts in the Infant Gut Microbiome

Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response. Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children. Here we describe high-resolution culture-independent analysis of stool samples from 6-month old infants fed daily supplements of Lactobacillus casei subsp. Rhamnosus (LGG) or placebo in a double-blind, randomized Trial of Infant Probiotic Supplementation (TIPS). Bacterial community composition was examined using a high-density microarray, the 16S rRNA PhyloChip, and the microbial assemblages of infants with either high or low LGG abundance were compared. Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species, and were significantly more even in their distribution of community members. Ecologically, these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens. PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy, as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species. From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable, even, and functionally redundant infant gastrointestinal community

Maternal characteristics associated with the dietary intake of nitrates, nitrites, and nitrosamines in women of child-bearing age: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Multiple <it>N</it>-nitroso compounds have been observed in animal studies to be both mutagenic and teratogenic. Human exposure to <it>N</it>-nitroso compounds and their precursors, nitrates and nitrites, can occur through exogenous sources, such as diet, drinking water, occupation, or environmental exposures, and through endogenous exposures resulting from the formation of <it>N</it>-nitroso compounds in the body. Very little information is available on intake of nitrates, nitrites, and nitrosamines and factors related to increased consumption of these compounds.</p> <p>Methods</p> <p>Using survey and dietary intake information from control women (with deliveries of live births without major congenital malformations during 1997-2004) who participated in the National Birth Defects Prevention Study (NBDPS), we examined the relation between various maternal characteristics and intake of nitrates, nitrites, and nitrosamines from dietary sources. Estimated intake of these compounds was obtained from the Willet Food Frequency Questionnaire as adapted for the NBDPS. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the consumption of these compounds by self-reported race/ethnicity and other maternal characteristics.</p> <p>Results</p> <p>Median intake per day for nitrates, nitrites, total nitrites (nitrites + 5% nitrates), and nitrosamines was estimated at 40.48 mg, 1.53 mg, 3.69 mg, and 0.472 μg respectively. With the lowest quartile of intake as the referent category and controlling for daily caloric intake, factors predicting intake of these compounds included maternal race/ethnicity, education, body mass index, household income, area of residence, folate intake, and percent of daily calories from dietary fat. Non-Hispanic White participants were less likely to consume nitrates, nitrites, and total nitrites per day, but more likely to consume dietary nitrosamines than other participants that participated in the NBDPS. Primary food sources of these compounds also varied by maternal race/ethnicity.</p> <p>Conclusions</p> <p>Results of this study indicate that intake of nitrates, nitrites, and nitrosamines vary considerably by race/ethnicity, education, body mass index, and other characteristics. Further research is needed regarding how consumption of foods high in nitrosamines and <it>N</it>-nitroso precursors might relate to risk of adverse pregnancy outcomes and chronic diseases.</p

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Interventions for educating children who are at risk of asthma-related emergency department attendance

Asthma is the most common chronic childhood illness and is a leading cause for paediatric admission to hospital. Asthma management for children results in substantial costs. There is evidence to suggest that hospital admissions could be reduced with effective education for parents and children about asthma and its management. The objective was to conduct a systematic review of the literature and update the previous review as to whether asthma education leads to improved health outcomes in children who have attended the emergency room for asthma. We searched the Cochrane Airways Group Trials Register, including the MEDLINE, EMBASE and CINAHL databases, and reference lists of trials and review articles (last search May 2008). We included randomised controlled trials of asthma education for children who had attended the emergency department for asthma, with or without hospitalisation, within the previous 12 months. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We pooled dichotomous data with a fixed-effect risk ratio. We used a random-effects risk ratio for sensitivity analysis of heterogenous data. A total of 38 studies involving 7843 children were included. Following educational intervention delivered to children, their parents or both, there was a significantly reduced risk of subsequent emergency department visits (RR 0.73, 95% CI 0.65 to 0.81, N = 3008) and hospital admissions (RR 0.79, 95% CI 0.69 to 0.92, N = 4019) compared with control. There were also fewer unscheduled doctor visits (RR 0.68, 95% CI 0.57 to 0.81, N = 1009). Very few data were available for other outcomes (FEV1, PEF, rescue medication use, quality of life or symptoms) and there was no statistically significant difference between education and control. Asthma education aimed at children and their carers who present to the emergency department for acute exacerbations can result in lower risk of future emergency department presentation and hospital admission. There remains uncertainty as to the long-term effect of education on other markers of asthma morbidity such as quality of life, symptoms and lung function. It remains unclear as to what type, duration and intensity of educational packages are the most effective in reducing acute care utilisation

Minimizing the Relationship Between Early Formula Use and Breastfeeding Cessation by Limiting Formula Volume

Objective: Early exposure to formula can interfere with successful long-term breastfeeding. The objective of this study was to determine whether limiting the volume of formula used in the first month attenuates formula\u27s detrimental impact on long-term breastfeeding success. Materials and Methods: Using detailed data on dietary intake from a randomized clinical trial, we conducted a secondary analysis of the association between volume of formula received in the first month and breastfeeding cessation before 6 and 12 months of age. We used descriptive statistics and multivariable logistic regression, respectively, to explore this association without and with adjustment for demographic and clinical predictors of infant feeding. Results: Among 199 breastfeeding infants, 80 (40%) received formula daily at 1 month of age, and breastfeeding cessation before 6 and 12 months of age was higher for these infants (46% and 67%) than for those breastfed exclusively (6% and 27%) (p \u3c 0.0005 for each). The risk of cessation did not differ between those who receive

Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial.

ObjectivesTo determine if probiotic administration during the first 6 months of life decreases childhood asthma and eczema.MethodsWe conducted a randomized, double-blind controlled trial of Lactobacillus rhamnosus GG (LGG) supplementation on the cumulative incidence of eczema (primary end point) and asthma and rhinitis (secondary end points) in high-risk infants. For the first 6 months of life, intervention infants (n = 92) received a daily dose of 10 billion colony-forming units of LGG and 225 mg of inulin (Amerifit Brands, Cromwell, CT), and control infants (n = 92) received 325 mg of inulin alone. We used survival analysis methods to estimate disease incidences in the presence or absence of LGG and to estimate the efficacy of LGG in delaying or preventing these diseases.ResultsInfants were accrued over a 6-year period (median follow-up: 4.6 years; 95% retention rate at 2 years). At 2 years of age, the estimated cumulative incidence of eczema was 30.9% (95% confidence interval [CI], 21.4%-40.4%) in the control arm and 28.7% (95% CI, 19.4%-38.0%) in the LGG arm, for a hazard ratio of 0.95 (95% CI, 0.59-1.53) (log-rank P = .83). At 5 years of age, the cumulative incidence of asthma was 17.4% (95% CI, 7.6%-27.1%) in the control arm and 9.7% (95% CI, 2.7%-16.6%) in the LGG arm, for a hazard ratio of 0.88 (95% CI, 0.41-1.87) (log-rank P = .25).ConclusionsFor high-risk infants, early LGG supplementation for the first 6 months of life does not appear to prevent the development of eczema or asthma at 2 years of age

Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial

ObjectivesTo determine if probiotic administration during the first 6 months of life decreases childhood asthma and eczema.MethodsWe conducted a randomized, double-blind controlled trial of Lactobacillus rhamnosus GG (LGG) supplementation on the cumulative incidence of eczema (primary end point) and asthma and rhinitis (secondary end points) in high-risk infants. For the first 6 months of life, intervention infants (n = 92) received a daily dose of 10 billion colony-forming units of LGG and 225 mg of inulin (Amerifit Brands, Cromwell, CT), and control infants (n = 92) received 325 mg of inulin alone. We used survival analysis methods to estimate disease incidences in the presence or absence of LGG and to estimate the efficacy of LGG in delaying or preventing these diseases.ResultsInfants were accrued over a 6-year period (median follow-up: 4.6 years; 95% retention rate at 2 years). At 2 years of age, the estimated cumulative incidence of eczema was 30.9% (95% confidence interval [CI], 21.4%-40.4%) in the control arm and 28.7% (95% CI, 19.4%-38.0%) in the LGG arm, for a hazard ratio of 0.95 (95% CI, 0.59-1.53) (log-rank P = .83). At 5 years of age, the cumulative incidence of asthma was 17.4% (95% CI, 7.6%-27.1%) in the control arm and 9.7% (95% CI, 2.7%-16.6%) in the LGG arm, for a hazard ratio of 0.88 (95% CI, 0.41-1.87) (log-rank P = .25).ConclusionsFor high-risk infants, early LGG supplementation for the first 6 months of life does not appear to prevent the development of eczema or asthma at 2 years of age