Faecal microbiota of individuals with autism spectrum disorder

Many children with autistic spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain. Such symptoms may be due to a disruption of the indigenous gut microbiota promoting the overgrowth of potentially pathogenic micro-organisms. These observations have stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. The purpose of the present study was to determine if a relationship exists between ASD severity (mild – severe) and GI microbial populations. The faecal microbiota of 22 male and 6 female participants with ASDs (aged 7 ± 6 years) were analyzed by standard microbial culture methods and compared within-group (based on ASD severity) and with a standard laboratory reference range. Comparisons between children with mild ASD and those with moderate to severe ASD, as well as comparisons to a neurotypical control group previously reported, revealed that no significant differences appear to exist in the composition of the gut microbiota. Nevertheless, examination of each individual’s gut microbial composition showed 10 cases of unusual findings witch means 1out of 3 cases have unusual microbiota. Our data do not support consistent GI microbial abnormalities in ASD children, but the findings do suggest that aberrations may be found in a minority subset of ASD children. Further studies are required to determine the possible association between the microbiota and gastrointestinal dysfunctions in a subset of children with both ASD and gastro-intestinal problems

Evaluation of biogenic amines in the faeces of children with and without autism by LC-MS/MS

Previous researchers have postulated that gastrointestinal bacteria may contribute to the development and maintenance of Autism Spectrum Disorders (ASD). There is evidence based on quantitative evaluation of the gastrointestinal bacterial population in ASD that this is unlikely and an alternate mechanism will be examined where the bacteria may contribute to the development of ASD via their metabolic products and the role of biogenic amines (BAs) will be investigated. In humans, BAs influence a number of physiological processes via their actions as neurotransmitters, local hormones and gastric acid secretion. Various amines have been implicated in several medical conditions such as schizophrenia and colon cancer. To date, the relationship between BAs and autism has not been explored. This study has been designed to identify differences (and/or similarities) in the level of Bas in faecal samples of autistic children (without gastrointestinal dysfunction: n = 14; with gastrointestinal dysfunction; n = 21) and their neurotypical siblings (n = 35) by LC-MS/MS. Regardless of the diagnosis, severity of ASD and gastrointestinal dysfunction there were no significant differences found between the groups. The findings suggest that BAs in the gastrointestinal tract do not play a role in the pathophysiology of gastrointestinal dysfunction associated with ASD

Effect of Bacilli Calmette-Guerin vaccine on severe combined immunodeficiency patient: a narrative review and proposed workup algorithm

This systematic review critically investigates the administration of the Bacillus Calmette-Guérin (BCG) vaccine in neonates with severe combined immunodeficiency (SCID). The BCG vaccine, derived from Mycobacterium bovis, is a live attenuated vaccine recognized for its significant role in mitigating the impacts of tuberculosis (TB) in endemic areas. Despite its beneficial effects in controlling TB, safety and efficacy concerns have been raised when the vaccine is administered to SCID patients, who have a severe dysfunction or absence of the immune system. The potential for the vaccine to lead to severe complications due to the immunocompromised state of SCID patients necessitates a comprehensive investigation. To better understand these issues, a thorough literature review was carried out, integrating data from clinical trials and observational studies available on the PubMed database. An extensive review and analysis of 32 relevant articles revealed substantial evidence of complications from BCG vaccination in SCID patients. These findings emphasize the urgency for a more effective pre-vaccination screening process to circumvent potential adverse effects. Given the crucial role of the BCG vaccine in controlling TB, its potential to induce severe complications in SCID patients warrants careful consideration. Therefore, this review proposes an in-depth screening algorithm for newborns before BCG vaccination administration. The goal is to prevent these adverse events, offering critical insights to health policymakers, researchers, and clinicians in the field

Mesoamerican nephropathy: a narrative review

Mesoamerican nephropathy (MeN) also known as chronic kidney disease of unknown etiology (CKDu) is prevalent in agriculturally rich areas. The most widely accepted pathophysiological explanation for MeN is chronic dehydration caused by prolonged exposure to the sun. Other theories include oxidative stress, chronic inflammation, infection and tubulointerstitial fibrosis. The clinical presentation is quite vague and is diagnosed similar to CKD from any cause using blood, urine analysis and ultrasound. The study highlights the need for interdisciplinary cooperation among physicians, epidemiologists, toxicologists, and geneticists while identifying significant research gaps and future objectives. Occupational health related to agriculture is not emphasised enough especially in third world countries where a large chunk of population heavily depend on farming. To safeguard the population at risk, the significance of community-based initiatives, occupational health measures, and regulatory changes is emphasised

An Integrative Cross-Omics Analysis of DNA Methylation Sites of Glucose and Insulin Homeostasis

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D

Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study

Background: Short-duration exposure to ambient particulate matter (PM) air pollution is associated with cardiac autonomic dysfunction and prolonged ventricular repolarization. However, associations with sub-chronic exposures to coarser particulates are relatively poorly characterized as are molecular mechanisms underlying their potential relationships with cardiovascular disease. Materials and methods: We estimated associations between monthly mean concentrations of PM < 10 μm and 2.5–10 μm in diameter (PM10; PM2.5-10) with time-domain measures of heart rate variability (HRV) and QT interval duration (QT) among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities Study (nHRV = 82,107; nQT = 76,711). Then we examined mediation of the PM-HRV and PM-QT associations by DNA methylation (DNAm) at three Cytosine-phosphate-Guanine (CpG) sites (cg19004594, cg24102420, cg12124767) with known sensitivity to monthly mean PM concentrations in a subset of the participants (nHRV = 7,169; nQT = 6,895). After multiply imputing missing PM, electrocardiographic and covariable data, we estimated associations using attrition-weighted, linear, mixed, longitudinal models adjusting for sociodemographic, behavioral, meteorological, and clinical characteristics. We assessed mediation by estimating the proportions of PM-HRV and PM-QT associations mediated by DNAm. Results: We found little evidence of PM-HRV association, PM-QT association, or mediation by DNAm. Conclusions: The findings suggest that among racially/ethnically and environmentally diverse U.S. populations, sub-chronic exposures to coarser particulates may not exert appreciable, epigenetically mediated effects on cardiac autonomic function or ventricular repolarization. Further investigation in better-powered studies is warranted, with additional focus on shorter duration exposures to finer particulates and non-electrocardiographic outcomes among relatively susceptible populations

Leukocyte traits and exposure to ambient particulate matter air pollution in the women’s health initiative and atherosclerosis risk in communities study

BACKGROUND: Inflammatory effects of ambient particulate matter (PM) air pollution exposures may underlie PM-related increases in cardiovascular disease risk and mortality, although evidence of PM-associated leukocytosis is inconsistent and largely based on small, cross-sectional, and/or unrepresentative study populations. OBJECTIVES: Our objective was to estimate PM–leukocyte associations among U.S. women and men in the Women’s Health Initiative and Atherosclerosis Risk in Communities study (n = 165,675). METHODS: We based the PM–leukocyte estimations on up to four study visits per participant, at which peripheral blood leukocytes and geocoded address-specific concentrations of PM ≤ 10, ≤2:5, and 2:5–10 lm in diameter (PM10, PM2:5, and PM2:5–10, respectively) were available. We multiply imputed missing data using chained equations and estimated PM–leukocyte count associations over daily to yearly PM exposure averaging periods using center-specific, linear, mixed, longitudinal models weighted for attrition and adjusted for sociodemographic, behavioral, meteorological, and geographic covariates. In a subset of participants with available data (n = 8,457), we also estimated PM–leukocyte proportion associations in compositional data analyses. RESULTS: We found a 12 cells=lL (95% confidence interval: −9, 33) higher leukocyte count, a 1.2% (0.6%, 1.8%) higher granulocyte proportion, and a −1:1% (−1:9%, −0:3%) lower CD8+ T-cell proportion per 10-lg=m3 increase in 1-month mean PM2:5. However, shorter-duration PM10 exposures were inversely and only modestly associated with leukocyte count. DISCUSSION: The PM2:5 –leukocyte estimates, albeit imprecise, suggest that among racially, ethnically, and environmentally diverse U.S. populations, sustained, ambient exposure to fine PM may induce subclinical, but epidemiologically important, inflammatory effects. https://doi.org/10.1289/EHP5360