Oxidative Stress In Children Research Articles

Vitamin D Status and Oxidative Stress in Children with Sickle Cell Anaemia in Sagamu, Nigeria

Objectives: Sickle cell anaemia (SCA) is characterized by nutritional deficiencies and oxidative stress. Vitamin D possesses antioxidant properties but its role in SCA in sub-Saharan Africa has not been fully understood. The relationship between Vitamin D status, oxidative stress and antioxidants status in children with SCA was investigated for its possible role in reducing complications arising from oxidative stress in SCA. Methods: Case-control study involving 100 HbS genotype and 100 HbA genotype children (control) of comparable age (5-12 years). Baseline characteristics were obtained and serum vitamin D, calcium, CAT, SOD, GPX, GST and XO levels were quantified by standard laboratory methods. Results: Serum levels of vitamin D, calcium, CAT, SOD, GPX and GST were significantly lower in SCA group compared to the control, while the XO level was significantly higher in the HbS group compared with control. There was positive correlation between vitamin D, CAT and SOD (r = 0.821, 0.869), weak positive association between vitamin D and Ca (r = 0.545) and no significant relationship between vitamin D and other measurands in the SCA group. Conclusion: Sufficient vitamin D status might impact positively on the antioxidant status in SCA individuals thereby reducing associated complications.

Oxidative stress in children with autism spectrum disorder – Pilot study

Oxidative stress in children with autism spectrum disorder – Pilot study

Metabolic Syndrome, Inflammation, Oxidative Stress, and Vitamin D Levels in Children and Adolescents with Obesity.

Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or obesity were analyzed for serum vitamin D, C-reactive protein, leukocytes, adiponectin, monocyte chemoattractant protein-1, myeloperoxidase, interferon-inducible T-cell alpha chemoattractant (I-TAC/CXCL11), superoxide dismutase-1, fasting lipid and glucose levels, ultrasound-measured abdominal fat thickness, waist circumference, body mass index and blood pressure. Children with obesity or overweight had lower vitamin D levels, increased blood pressure, visceral and subcutaneous fat thickness, and higher leukocytes, C-reactive protein, and myeloperoxidase levels. Those with MetS also had lower adiponectin levels. Vitamin D levels are negatively correlated with body mass index, waist circumference, and visceral and subcutaneous fat thickness. Correlation, mediation, and regression analyses showed no link between vitamin D and inflammatory/oxidative stress variables. The novel biomarker I-TAC did not correlate with obesity or vitamin D status. Our results indicate that vitamin D does not significantly mediate inflammation or oxidative stress in children and adolescents with obesity and/or MetS. Selected inflammation/oxidative stress biomarkers appear to be altered primarily due to obesity rather than vitamin D status.

Assessment of 8-Hydroxy-2’-Deoxyguanosine (8-OH-dG) Level in Urine as a Urinary Marker of Oxidative Stress in Children with Autism Spectrum Disorder

Abstract Background Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction, restricted interest and repetitive behavior. Oxidative stress in response to environmental exposure plays a role in virtually every human disease and represents a significant avenue of research into the etiology of ASD. Objective The aim of this study was to asses 8-hydroxy-2’-deoxyguanosine (8-OH-dG) level in urine as a urinary marker of oxidative stress in children with autism spectrum disorder in comparison to sex and age matched healthy control group. Patients and Methods We included 51 children with autism (43 males and 8 females whose age ranged from 2 to 16 years). They were compared to 51 children of the same age as a control group. The diagnosis of autism was made based on the criteria of autistic disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSMV). In the patients group, detailed medical history included sociodemographic form and family history was taken for autistic group also Intelligence Quotient test IQ test and Childhood Autism Rating Scale (CARS) used to measure the severity of autism. In the study, 8-OHdG values in urine were investigated using the enzyme-linked immunosorbent assay (ELISA) method and Urinary creatinine was determined with the Beckham Coulter analyzer and was used to normalize all biochemical measurements then the urinary 8-OHdG/creatinine levels were corrected to the urinary concentration of creatinine. Results The median age was 9.9 in the ASD group and 9.1 in the control group (P = 0.256). In the ASD group, (8-OH-dG)/creatinine ratio values were found to be significantly higher than those of the controls (P < 0.001). but also No statistically significant correlation between (8-OH- dG)/creatinie ratio and CARS score or IQ score (P = 0,7). Conclusion The data from this study supported the hypothesis of the oxidant/antioxidant balance as a key piece that may contribute to the autistic pathology

Do heavy metals have a role in extrahepatic portal vein obstruction in children: A pilot case-control study

ObjectiveExtrahepatic portal venous obstruction (EHPVO) is a common cause of portal hypertension in Southeast Asia as compared to the western world, where chronic liver disease is the most common cause. Pollution and inadvertent exposure to heavy metals in poor socio-economic status in this part of the world are quite common. Therefore, this study was proposed to determine the association between heavy metal levels and oxidative stress in children with EHPVO. MethodsThis pilot case-control study was conducted in the department of Pediatrics, of a tertiary health care centre from January 2020 to October 2021. Children between 1 and 14 years, diagnosed with EHPVO were included. Controls were the healthy volunteers from OPD and near discharge indoor pediatrics patients. Metal analysis for Copper, Lead, Zinc, and Manganese, & Antioxidant activity for superoxide dismutase (SOD), Glutathione reductase (GR) and Lipid peroxidase (LPO) in form of malondialdehyde (MDA) was measured in both the groups. ResultsA total of 80 subjects were enrolled (40 EHPVO cases and 40 controls) mean age for cases was 8.15 ± 3.53, and for control, was 7.69 ± 3.55 years (p = 0.560). Lead values were found to be significantly higher (p = 0.003) in EHPVO cases (5.39 ± 3.13) in comparison to controls (3.30 ± 2.91). Mean superoxide dismutase (SOD) and Glutathione reductase (GR) values were decreased (p = 0.035- GR) and the malondialdehyde (MDA) value was increased in the EHPVO cases as compared to controls. ConclusionChildren with high blood levels of lead might be at risk of portal vein thrombosis resulting in EHPVO, and lead-induced oxidative stress.

Nasal oxidative stress mediating the effects of colder temperature exposure on pediatric asthma symptoms.

Colder temperature exposure is a known trigger for pediatric asthma exacerbation. The induction of oxidative stress is a known pathophysiologic pathway for asthma exacerbation. However, the role of oxidative stress in linking colder temperature exposure and worsened pediatric asthma symptoms is poorly understood. In a panel study involving 43 children with asthma, aged 5-13 years old, each child was visited 4 times with a 2-week interval. At each visit, nasal fluid, urine, and saliva samples were obtained and measured for biomarkers of oxidative stress in the nasal cavity (nasal malondialdehyde [MDA]), the circulatory system (urinary MDA), and the oral cavity (salivary MDA). Childhood Asthma-Control Test (CACT) was used to assess asthma symptoms. When ambient daily-average temperature ranged from 7 to 18 °C, a 2 °C decrement in personal temperature exposures were significantly associated with higher nasal MDA and urinary MDA concentrations by 47-77% and 6-14%, respectively. We estimated that, of the decrease in child-reported CACT scores (indicating worsened asthma symptoms and asthma control) associated with colder temperature exposure, 14-57% were mediated by nasal MDA. These results suggest a plausible pathway that colder temperature exposure worsens pediatric asthma symptoms partly via inducing nasal oxidative stress. The role of oxidative stress in linking colder temperature exposure and worsened asthma symptoms is still poorly understood. Lower temperature exposure in a colder season was associated with higher nasal and systemic oxidative stress in children with asthma. Nasal MDA, a biomarker of nasal oxidative stress, mediated the associations between colder temperature exposures and pediatric asthma symptoms. The results firstly suggest a plausible pathway that colder temperature exposure worsens pediatric asthma symptoms partly via inducing oxidative stress in the nasal cavity.

New Clinical Markers of Oxidized Lipid-Associated Protein Damage in Children and Adolescents with Obesity.

Obesity in children and adolescents has been associated with oxidative stress (OS). The lipid hydroperoxides (LOOH) and the malondialdehyde (MDA) and thiobarbituric reactive substances (TBARS) that oxidatively modify proteins (Pr) (i.e., PrMDA and PrTBARS, respectively) represent markers of OS-associated lipid peroxidation. We aimed to assess OS in children and adolescents with obesity using-for the first time-markers involved in the early and late lipid oxidation process. LOOH, PrMDA, and PrTBARS were investigated in 41 children and adolescents with obesity and 31 controls. Obesity was defined as BMI > 95% for age and sex. The PrMDA/PrTBARS pair, which reflects a late peroxidation stage, was found to be significantly high (39%/180%) in children and adolescents with obesity compared to controls (p < 0.001). Similarly, the early LOOH peroxidation stage marker was increased by 30%. The studied OS parameters were not influenced by sex or age. Our study introduces LOOH, PrTBARS, and PrMDA as markers for evaluating OS in children and adolescents with obesity. LOOH, PrTBARS, and PrMDA may also hold promise as prognostic markers for potential obesity-associated long-term complications.

TOTAL ANTIOXIDANT CAPACITY MAY NOT BE AN ACCURATE WAY TO PREDICT DENTAL CARIES

Salivary biomarkers of oxidative stress in children with dental caries: Systematic review and meta-analysis doi:10.1016/j.archoralbio.2022.105432. CAPES (Coordination for the improvement of higher education, National Council of Technological and Scientific Development), Finace code 001. Systematic review with meta-analysis of data.

Breath Markers of Oxidative Stress in Children with Severe Viral Lower Respiratory Tract Infection.

Severe viral lower respiratory tract infection (LRTI), resulting in both acute and long-term pulmonary disease, constitutes a substantial burden among young children. Viral LRTI triggers local oxidative stress pathways by infection and inflammation, and supportive care in the pediatric intensive care unit may further aggravate oxidative injury. The main goal of this exploratory study was to identify and monitor breath markers linked to oxidative stress in children over the disease course of severe viral LRTI. Exhaled breath was sampled during invasive ventilation, and volatile organic compounds (VOCs) were analyzed using gas chromatography and mass spectrometry. VOCs were selected in an untargeted principal component analysis and assessed for change over time. In addition, identified VOCs were correlated with clinical parameters. Seventy breath samples from 21 patients were analyzed. A total of 15 VOCs were identified that contributed the most to the explained variance of breath markers. Of these 15 VOCs, 10 were previously linked to pathways of oxidative stress. Eight VOCs, including seven alkanes and methyl alkanes, significantly decreased from the initial phase of ventilation to the day of extubation. No correlation was observed with the administered oxygen dose, whereas six VOCs showed a poor to strong positive correlation with driving pressure. In this prospective study of children with severe viral LRTI, the majority of VOCs that were most important for the explained variance mirrored clinical improvement. These breath markers could potentially help monitor the pulmonary oxidative status in these patients, but further research with other objective measures of pulmonary injury is required.

Effect of Supervised Physical Exercise on Oxidative Stress in Children with Autism

Background: The etiology of autism spectrum disorders is not well known but oxidative stress has been suggested to play a pathological role. Purpose: The present study aimed to investigate the effects of supervised physical exercise on oxidative stress in children with autism. Methods: Thirty boys with autism (7 to 9 years old) voluntarily participated in this study. They were randomly divided into experimental and control groups. The experimental group performed a physical curriculum known as sports, play and active recreation for kids (SPARK) for 12 weeks (3 sessions of 45 minutes per week), while the control group was exempted to participate in the program. As the clinical parameters, the level of brain-derived neurotrophic factor (BDNF) and malondialdehyde (MDA) were measured before and after the intervention. Results: The results indicated that BDNF levels significantly increased (85.7 %) and MDA concentration significantly decreased (29.2%) in the experimental group (p &lt; 0.05). Conclusions: In conclusion, the supervised physical exercise may result in less oxidative stress in children with autism.

Markers of oxidative stress in children with iron deficiency anemia

BackgroundOxidative stress can occur in iron deficiency anemia (IDA), causing cellular injury. The primary objective of the study was to assess serum malondialdehyde (MDA), protein carbonyl as oxidants and glutathione reductase catalase, superoxide dismutase (SOD), and vitamin C levels as antioxidants in patients with IDA and healthy controls; and secondary objectives were to observe the levels among the mild, moderate and severe category of IDA and their correlations with serum iron and ferritin. Material and methodsFifty-five patients of IDA and 50 healthy controls were enrolled. Diagnosis of IDA was made based on the cut-off values of low hemoglobin as per age, serum iron <30 μg/dL, ferritin <12 ng/mL, and transferrin saturation <16 %. Serum levels of MDA, protein carbonyl, glutathione reductase, catalase, SOD, and vitamin C were estimated. ResultsThe median age of patients and controls was 6 years. IDA patients had significantly raised mean levels of MDA (p < 0.001) and protein carbonyl (p < 0.001) and decreased glutathione reductase (p < 0.001), catalase (p < 0.001), SOD (p = 0.014) and vitamin C (p = 0.010) than controls. Parameters were comparable among mild, moderate, and severe degrees of IDA. Significantly negative correlations of MDA (r = −0. 713, p < 0.001, −0.683 p < 0.001) and protein carbonyl (r = −0.500, p < 0.001, - 0.519, p < 0.001) and positive correlations of glutathione reductase (r = 0.607, p < 0.001, 0.629, p < 0.001), catalase (r = 0.447, p < 0.001, 0.436, p < 0.001), SOD (r = 0.209, p = 0.032, 0.175, p = 0.075) and vitamin C (r = 0.233,p = 0.017, 0.197, p = 0.044) were observed with serum iron and ferritin, respectively. ConclusionOxidative stress exists in patients with IDA, unaffected by the severity of anemia, and has significant correlations with serum iron and ferritin concentrations.

The Impact of Competitive Sports on Oral Health: Exploring Their Relationship with Salivary Oxidative Stress in Children.

This article explores the correlation between salivary biomarkers, such as glutathione peroxidase (GPX), total antioxidant capacity (TAC), and superoxide dismutase (SOD), and their association with oral health for children in competitive sports. Saliva has emerged as a valuable resource for evaluating physiological and pathological conditions due to its non-invasive collection method and easy storage. This study examines the potential of GPX, TAC, and SOD as salivary biomarkers for assessing the impact of competitive sports on children's oral health. It discusses the potential implications of increased oxidative stress due to intense physical activity and the role of antioxidant defense mechanisms in maintaining oral health. In total, 173 children aged between 6 and 17 were divided into three groups, 58 hockey players, 55 football players, and 60 in the control group, and examined to assess their oral hygiene and dental and periodontal health. Saliva was collected, centrifuged, and the supernatant was analyzed for the relevant biomarkers. The findings seem to suggest that salivary biomarkers, like GPX, TAC, and SOD, might serve as indicators of the physiological response to competitive sports in children, as well as indicators of oral health, especially dental cavities, and periodontal disease. Statistical analysis showed significant differences between the groups, with better values for athletes, regardless of age, sex, or activity type. Understanding the relationship between salivary biomarkers and competitive sports in children can have significant implications for monitoring and optimizing the health and performance of young athletes. Further research is needed to establish the specific associations between these biomarkers and the effects of several types and intensities of sports activities on oral health in children.

Beta glucan as supplement treatment decreases oxidative stress in children with allergic rhinitis treated with corticosteroids

Beta glucan as supplement treatment decreases oxidative stress in children with allergic rhinitis treated with corticosteroids

Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children.

To determine immune-metabolic dysregulation in children born to women living with HIV. Longitudinal immune-metabolomic analyses of plasma of 32 pregnant women with HIV (WHIV) and 12 uninfected women and their children up to 1.5 years of age were performed. Using liquid chromatography-mass spectrometry and a multiplex bead assay, 280 metabolites (57 amino acids, 116 positive lipids, 107 signalling lipids) and 24 immune mediators (e.g. cytokines) were quantified. combinational antiretroviral therapy (cART) exposure was categorized as cART initiation preconception (long), cART initiation postconception up to 4 weeks before birth (medium) and cART initiation within 3 weeks of birth (short). Plasma metabolite profiles differed between HIV-exposed-uninfected (HEU)-children with long cART exposure compared to HIV-unexposed-children (HUU). Specifically, higher levels of methionine-sulfone, which is associated with oxidative stress, were detected in HEU-children with long cART exposure compared to HUU-children. High infant methionine-sulfone levels were reflected by high prenatal plasma levels in the mother. Increased methionine-sulfone levels in the children were associated with decreased growth, including both weight and length. These findings based on longitudinal data demonstrate that dysregulation of metabolite networks associated with oxidative stress in children born to WHIV is associated with restricted infant growth.

EFFECT OF NASAL CORTICOSTEROIDS ON OXIDATIVE STRESS PARAMETERS IN CHILDREN WITH ALLERGIC RHINITS

Oxidative stress (OS) is a result of an imbalance between the production of free radicals and the antioxidant defense mechanisms in the organism. Allergic rhinitis (AR) is characterized by chronic inflammation and increased presence of eosinophils, basophils and mast cells in nasal secretions and mucosa. Stimulation of these cells results in production of free radicals (reactive oxygen metabolites). The aim of this study was to determine the level of OS and antioxidant capacity in children with AR after 8 weeks treatment with nasal corticosteroid (NCS). Thirty children with AR (mean age 8.3 ± 2.9 years) were included. The FRAS 5 Bravo system was used to determine the OS parameters. Demographic characteristics, medical history, children's living conditions and eating habits were obtained from the questionarrie. Anthropometric measurements, absolute number of eosinophils in the peripheral smear and eosinophils in nasal smear were performed in each child. The mean value of blood concentration of serum peroxides (d-ROMs) was 403.4 ± 91.3 U. Carr, while the mean value of OS index was 95.1 ± 45.9. After 8 weeks of treatment with NCS, the mean values were 337.6 ± 71.9 U. Carr, and 53.6 ± 28.3, respectively. Both parameters had significantly lower values (p&lt;0.05) compared to those before the initiation of NCS therapy. After treatment, a significant improvement in the symptoms score of AR was detected (p&lt;0.05). NCS therapy makes asignificant improvement of the symptoms and a considerable reduction in the OS in children with AR. Keywords: allergic rhinitis, children, oxidative stress, d-ROMs, PAT, OSI

Evaluation of Thiol/Disulfide Homeostasis and Neurogenin 3 Levels as a Marker of Oxidative Stress in Children and Adolescents Newly Diagnosed with Type 1 Diabetes

The objective of the study was to determine the relationship between autoimmunity and dynamic thiol/disulfide, neurogenin 3 (ngn 3) status in the newly diagnosed with type 1 diabetes mellitus (T1DM), the level of treatment, and thiol/disulfide homeostasis and neurogenin 3, and to found the changes in neurogenin 3 level due to beta cell damage in children newly diagnosed with T1DM. Totally 60 children aged 1-18 years old, 30 of them newly diagnosed with type 1 diabetes (patients), and 30 of them healthy children in the same age group (control) were included in the study. Insulin and C-peptide levels of newly diagnosed T1DM patients were lower than the control group, however, HbA1c, glucose, creatinine, cholesterol, triglyceride, and LDL levels were found higher in patients. Total thiol level and Gad antibody positive rate were found higher in children newly diagnosed with T1DM. In addition, it was observed that the rate of anti-insulin antibody positivity increased in the 6th-month control of patients. However, HbA1c and glucose levels at diagnosis were higher in patients compared to the control group at the sixth month. Insulin and C-peptide levels were determined lower in patients admitted with diabetic ketoacidosis. A negative correlation was observed between native thiol and anti-insulin antibody parameters and a positive correlation between ngn 3 and total cholesterol and LDL. In conclusion, thiol/disulfide homeostasis and ngn 3 parameters can be used as oxidative stress markers in children and adolescents newly diagnosed with T1DM.

Impact of Arginine Therapy on Clinical Outcomes, Mitochondrial Function and Oxidative Stress in Children with Sickle Cell Disease Hospitalized with Vasoocclusive Pain Episodes: A Randomized Controlled Trial

Introduction: Vaso-occlusive pain episodes (VOE) are the leading cause of emergency department (ED) visits & hospitalization in patients with sickle cell disease (SCD). During SCD-VOE, patients develop an acute arginine (Arg) deficiency. Supplementation with Arg has shown opioid-sparing effects, improves blood pressure & cardiopulmonary function & decreases length of hospital stay. Though we have previously demonstrated that intravenous (IV) Arg improves mitochondrial (mito) function, the precise mechanisms by which Arg mediates these positive effects remain unclear. Objectives: To determine the role of IV Arg as adjuvant in the management of SCD-VOE Methods: Prospective single-center double-blind randomized controlled trial (RCT) of IV Arg (TID, up to 7 days) in children with SCD age 3-21 years hospitalized for VOE requiring IV opioids. Patients with significant liver/renal dysfunction or those previously enrolled were excluded. Subjects were randomized into 1 of 3 arms: 1) 100 mg/kg/dose Arg, standard dose (SD), 2) loading dose: 200 mg/kg followed by SD or 3) placebo. Demographics, total parenteral opioid (TPO) use (morphine equivalents, mg/kg) time to crisis resolution (time of study drug delivery to last IV opioid in hours), pain scores, patient reported outcomes (PROMIS) & mito function were obtained before treatment & at discharge. The primary outcome measure was TPO use between study arms. Hypothesis tests & unadjusted & covariate-adjusted fixed & mixed effects generalized linear regression models were used, as appropriate, to compare cross-sectional & longitudinal outcomes within & between randomization arms. This protocol utilized IND#66943 (Sponsor-Morris), registered with ClinicalTrials.gov (NCT02536170). Results: 1,548 patients were screened, 266 were eligible, 114 consented, & 108 were randomized. Safety results of this RCT have been previously reported (Reyes et al, Am J Hematol 2022). Demographics & clinical outcomes of subjects randomized by treatment arm are provided in Table 1. While statistically insignificant, there was a clinically relevant decrease in TPO & time to crisis resolution in both Arg arms compared to placebo. The placebo group required 45% higher TPO & experienced >15 hours longer mean time to crisis resolution compared to combined Arg-treated groups when adjusted for HU use, continuous age and sex. Among children <17 years, the placebo group (n=33) required 80% more TPO compared to combined Arg groups (n=57; p=0.075). No differences in ED vs discharge pain scores or patient/parent PROMIS reports across arms were found. Mito Complex V activity was higher (p=0.02) & protein carbonyl levels were lower (p=0.003) at ED visit in patients on Hydroxyurea (HU). Notably mito Complex IV & V activity increased significantly in both Arg arms while there was no change in the placebo group (Fig 1, p<0.001); protein carbonyl levels in platelet rich plasma decreased in both Arg groups (Fig 1, p<0.001), suggesting a decrease in oxidative stress that increased in the placebo arm (p=0.02). Greatest mito improvement occurred with Arg loading dose. Conclusion: Arg supplementation increases mito activity & decreases oxidative stress in children with SCD-VOE. This is the first report to suggest a HU-related impact on mito activity in SCD. Prior reports show that Complex V inhibition leads to increased mito oxidant production in platelets from SCD patients. Acute improvements in Complex IV & V function & decreased oxidative markers with Arg therapy are consistent with Arg-induced reductions in mito oxidant generation. Arg therapy improves symptoms associated with MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) suggesting an impact of Arg on mito activity that may be beneficial in SCD. Given emerging data supporting a link between mito function and pain, improved mito activity may mechanistically contribute to decreased pain & ultimately less opioid requirement with IV Arg treatment, as well as have further implications for improved metabolism and oxidative signaling in SCD. In this RCT, Arg therapy also demonstrated clinically relevant opioid-sparing & a decreased time to crisis resolution that was statistically insignificant. A larger sample size may elucidate potential differences; we are currently enrolling 360 children in an ongoing PECARN-endorsed multicenter Phase 3 RCT (SCD Treatment with Arg Therapy - STArT). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy

Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.

Kynurenine and oxidative stress in children having learning disorder with and without attention deficit hyperactivity disorder: possible role and involvement

BackgroundThe etiological and pathophysiological factors of learning disorder (LD) and attention deficit hyperactivity disorder (ADHD) are currently not well understood. These disorders disrupt some cognitive abilities. Identifying biomarkers for these disorders is a cornerstone to their proper management. Kynurenine (KYN) and oxidative stress markers have been reported to influence some cognitive abilities. Therefore, the aim was to measure the level of KYN and some oxidative stress indicators in children with LD with and without ADHD and to investigate their correlations with the abilities of children with LD.MethodsThe study included 154 participants who were divided into 3 groups: one for children who have LD (N = 69); another for children with LD and ADHD (N = 31); and a group for neurotypical (NT) children (N = 54). IQ testing, reading, writing, and other ability performance evaluation was performed for children with LD. Measuring plasma levels of KYN, malondialdehyde, glutathione peroxidase, and superoxide dismutase by enzyme-linked immunosorbent assay was performed for all participants.ResultsSome IQ measures and learning skills differed between the first two groups. The biochemical measures differed between children with LD (with and without ADHD) and NT children (p < 0.001). However, the biochemical measures did not show a significant statistical difference between the first two groups. KYN and glutathione peroxidase levels were correlated with one-minute writing and at-risk quotient, respectively (p = 0.03;0.04). KYN and malondialdehyde showed the highest sensitivity and specificity values.ConclusionThese biochemical measures could be involved or have a role in the abilities’ performance of children with specific learning disorder.

Associations between repeated measures of urinary phthalate metabolites and biomarkers of oxidative stress in a rural agricultural cohort of children with asthma

Phthalate exposure is widespread, and studies suggest an adverse relationship with asthma morbidity, including some support for oxidative stress as an underlying pathophysiological mechanism. Urinary phthalate metabolites have been associated with biomarkers of oxidative stress, but data are few in children diagnosed with asthma. We used participant data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine longitudinal relationships between phthalates and oxidative stress in a cohort of Latino children with asthma residing in an agricultural community. We used linear mixed-effects models to estimate associations between 11 urinary phthalate metabolites (and one summed measure of di-2-ethylhexyl phthalate (DEHP) metabolites, ∑DEHP) and two urinary biomarkers of oxidative stress: a biomarker of lipid peroxidation via measure of 8-isoprostane and a biomarker of DNA/RNA oxidative damage via combined measure of 8-hydroxydeoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 8-hydroxyguanine. Seventy-nine participants provided 281 observations. In covariate-adjusted models, we observed significant positive relationships between all phthalate metabolites and 8-isoprostane, effect sizes ranging from a 9.3 % (95 % CI: 4.2 %–14.7 %) increase in 8-isoprostane for each 100 % increase (i.e., doubling) of mono-(carboxy-isooctyl) phthalate (MCIOP), to a 21.0 % (95 % CI: 14.3 %–28.2 %) increase in 8-isoprostane for each doubling of mono-n-butyl phthalate (MNBP). For each doubling of mono-(carboxy-isononyl) phthalate (MCINP) and mono-ethyl phthalate (MEP), the DNA/RNA oxidative damage biomarker increased by 6.0 % (95 % CI: 0.2 %–12.2 %) and 6.5 % (95 % CI: 1.4 %–11.9 %), respectively. In conclusion, we provide unique data suggesting phthalate exposure is positively associated with oxidative stress in children with asthma. Our repeat measures provide novel identification of a consistent effect of phthalates on oxidative stress in children with asthma via lipid peroxidation. Confirmation in future studies of children with asthma is needed to enhance understanding of the role of phthalates in childhood asthma morbidity.