Influence of gut microbiota on immune system in infants

Background and Methods: Microbiota play many significant, direct or indirect, beneficial and detrimental roles in humans. Microbiome development is established at infancy where diet plays a directive role in the proliferation of gut microbes. It has been shown that the presence of a defined set of microbes has been known to increase the overall immunological capacity, which vaccines depend on to be effective. To date, little work has been done on the effect of the microbiota on immune system at infancy, thus an analysis of the microbial ecology present in the infant's gut and its correlation with immune activation is needed. Expression of genes involved in mediating and regulating immunity can be measured as an indicator of immune activity. Vaccines work by stimulating an immune response which can be measured by gene expression levels. This affects the infant's ability to establish a strong immune system, which is also dictated at infancy. 16s rRNA sequence data generated from 134 infant stool samples, at vaccination points 0, 6 and 14 weeks from infants that were either breast or formula fed, was analysed using the Quantitative Insights Into Microbial Ecology (QIIME) pipeline to detect different taxonomic groups that make up a particular microbiome. Statistical analysis in R was used to quantify the diversity of the different microbial groups in the gut. Expression levels of immune-related genes were measured from blood samples that were stimulated by a Bacillus Calmette–Guérin (BCG) antigen and correlated with microbiota compositions. Results and Conclusion: Microbiome data showed initial differentiation between breast and mixed fed infants.15% of 5 of the most abundant bacteria for breast fed infants were Bifidobacteriales, which are known for their probiotic properties. The data did not fully cluster as the oldest samples were taken quite early at 14 weeks. Individual bacteria were correlated with individual gene expression level data. The study shows the relative abundance of particular bacteria, comparing against feeding modality and demonstrated how the microbiota correlates with gene expression levels. At week 14, Bifidobacterium of abundance below 0 (heatmap log₁₀ scale) generally correlated with high CASP3 gene expression levels in breast fed babies while abundances above 1 correlated with low gene expression levels. Gene expression at abnormal levels usually has undesirable effects which result in dysfunctional immune reactions that lead to conditions ranging from autoimmune diseases to cancer

Frameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature

BACKGROUND: We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. RESULTS: Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject. CONCLUSIONS: We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis

Integrated human exposure to air pollution

The book “Integrated human exposure to air pollution” aimed to increase knowledge about human exposure in different micro-environments, or when citizens are performing specific tasks, to demonstrate methodologies for the understanding of pollution sources and their impact on indoor and ambient air quality, and, ultimately, to identify the most effective mitigation measures to decrease human exposure and protect public health. Taking advantage of the latest available tools, such as internet of things (IoT), low-cost sensors and a wide access to online platforms and apps by the citizens, new methodologies and approaches can be implemented to understand which factors can influence human exposure to air pollution. This knowledge, when made available to the citizens, along with the awareness of the impact of air pollution on human life and earth systems, can empower them to act, individually or collectively, to promote behavioral changes aiming to reduce pollutants’ emissions. Overall, this book gathers fourteen innovative studies that provide new insights regarding these important topics within the scope of human exposure to air pollution. A total of five main areas were discussed and explored within this book and, hopefully, can contribute to the advance of knowledge in this field

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes