Urinary carboxylic acids (UCAs) in subjects with autism spectrum disorder and their association with bacterial overgrowth

Abstract In this study, the levels of concentration of carboxylic acids (benzoic acid, p-hydroxybenzoic acid, p-hydroxyphenylacetic acid, and hippuric acid) in the urine of autistic children were investigated and compared. The increased excretion of carboxylic acids is related to excessive bacterial activity in the gut, called bacterial overgrowth, which has been related to autism spectrum disorder (ASD) as an impairment in the gut-brain axis. The investigation was based on the analysis of urine samples obtained from 120 ASD children. To identify and quantify urinary carboxylic acids (UCAs), we applied gas chromatography coupled with mass spectrometry (GC-MS). Additionally, we checked the influence of probiotic supplementation, gender, body mass index (BMI) value and age of children on the level of different selected compounds. Most of the obtained results were found within reference ranges. In some cases, the levels of benzoic acid, p-hydroxybenzoic acid, and p-hydroxyphenylacetic acid were particularly elevated. Statistically significant differences were observed in supplementation with probiotics and the level of p-hydroxyphenylacetic acid (p=0.036). The obtained results may indicate disturbances in the intestinal flora in some autistic patients and suggest that supplements may have an influence on the levels of carboxylic acids in urine. Due to the small population of children taking the supplement, further study are needed

Effect of Supplementation on Levels of Homovanillic and Vanillylmandelic Acids in Children with Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) are characterized by numerous comorbidities, including various metabolic and nutritional abnormalities. In many children with ASD, problems with proper nutrition can often lead to inadequate nutrient intake and some disturbances in metabolic profiles, which subsequently correlate with impaired neurobehavioural function. The purpose of this study was to investigate and compare the relationship between supplementation, levels of homovanillic acid (HVA) and vanillylmandelic acid (VMA) and the behaviour of children with ASD using quantitative urinary acid determination and questionnaires provided by parents/caregivers. The study was carried out on 129 children between 3 and 18 years of age. HVA and VMA were extracted and derivatized from urinary samples and simultaneously analyzed by gas chromatography-mass spectrometry (GC-MS). In addition, parents/caregivers of children with ASD were asked to complete questionnaires containing information about their diet and intake/non-intake of supplements. The application of the Mann–Whitney U test showed a statistically significant difference between the level of HVA and vitamin B supplementation (p = 1.64 × 10−2) and also omega-6 fatty acids supplementation and the levels of HVA (p = 1.50 × 10−3) and VMA (p = 2.50 × 10−3). In some children, a reduction in the severity of autistic symptoms (better response to own name or better reaction to change) was also observed. These results suggest that supplementation affects the levels of HVA and VMA and might also affect the children’s behaviour. Further research on these metabolites and the effects of supplementation on their levels, as well as the effects on the behaviour and physical symptoms among children with ASD is needed

Higher Levels of Low Molecular Weight Sulfur Compounds and Homocysteine Thiolactone in the Urine of Autistic Children

In this study, the levels of concentration of homocysteine thiolactone (HTL), cysteine (Cys), and cysteinylglycine (CysGly) in the urine of autistic and non-autistic children were investigated and compared. HTL has never been analyzed in autistic children. The levels of low molecular weight sulfur compounds in the urine of both groups were determined by validated methods based on high-performance liquid chromatography with spectrofluorometric and diode-array detectors. The statistical data show a significant difference between the examined groups. Children with autism were characterized by a significantly higher level of HTL (p = 5.86 × 10−8), Cys (p = 1.49 × 10−10) and CysGly (p = 1.06 × 10−8) in urine compared with the control group. A difference in the p-value of <0.05 is statistically significant. Higher levels of HTL, Cys, and CysGly in the urine of 41 children with autism, aged 3 to 17, were observed. The obtained results may indicate disturbances in the metabolism of methionine, Cys, and glutathione in some autistic patients. These preliminary results suggest that further research with more rigorous designs and a large number of subjects is needed

Urinary carboxylic acids (UCAs) in subjects with autism spectrum disorder and their association with bacterial overgrowth

In this study, the levels of concentration of carboxylic acids (benzoic acid, p-hydroxybenzoic acid, p-hydroxyphenylacetic acid, and hippuric acid) in the urine of autistic children were investigated and compared. The increased excretion of carboxylic acids is related to excessive bacterial activity in the gut, called bacterial overgrowth, which has been related to autism spectrum disorder (ASD) as an impairment in the gut-brain axis. The investigation was based on the analysis of urine samples obtained from 120 ASD children. To identify and quantify urinary carboxylic acids (UCAs), we applied gas chromatography coupled with mass spectrometry (GC-MS). Additionally, we checked the influence of probiotic supplementation, gender, body mass index (BMI) value and age of children on the level of different selected compounds. Most of the obtained results were found within reference ranges. In some cases, the levels of benzoic acid, p-hydroxybenzoic acid, and p-hydroxyphenylacetic acid were particularly elevated. Statistically significant differences were observed in supplementation with probiotics and the level of p-hydroxyphenylacetic acid (p=0.036). The obtained results may indicate disturbances in the intestinal flora in some autistic patients and suggest that supplements may have an influence on the levels of carboxylic acids in urine. Due to the small population of children taking the supplement, further study are needed

Plasma Metabolic Disturbances in Parkinson’s Disease Patients

Plasma from patients with Parkinson’s disease (PD) is a valuable source of information indicating altered metabolites associated with the risk or progression of the disease. Neurotoxicity of dopaminergic neurons, which is triggered by aggregation of α-synuclein, is the main pathogenic feature of PD. However, a growing body of scientific reports indicates that metabolic changes may precede and directly contribute to neurodegeneration. Identification and characterization of the abnormal metabolic pattern in patients’ plasma are therefore crucial for the search for potential PD biomarkers. The aims of the present study were (1) to identify metabolic alterations in plasma metabolome in subjects with PD as compared with the controls; (2) to find new potential markers, some correlations among them; (3) to identify metabolic pathways relevant to the pathophysiology of PD. Plasma samples from patients with PD (n = 25) and control group (n = 12) were collected and the gas chromatography-time-of-flight-mass spectrometry GC-TOFMS-based metabolomics approach was used to evaluate the metabolic changes based on the identified 14 metabolites with significantly altered levels using univariate and multivariate statistical analysis. The panel, including 6 metabolites (L-3-methoxytyrosine, aconitic acid, L-methionine, 13-docosenamide, hippuric acid, 9,12-octadecadienoic acid), was identified to discriminate PD from controls with the area under the curve (AUC) of 0.975, with an accuracy of 92%. We also used statistical criteria to identify the significantly altered level of metabolites. The metabolic pathways involved were associated with linoleic acid metabolism, mitochondrial electron transport chain, glycerolipid metabolism, and bile acid biosynthesis. These abnormal metabolic changes in the plasma of patients with PD were mainly related to the amino acid metabolism, TCA cycle metabolism, and mitochondrial function

Effect of Zinc Supplementation on the Serum Metabolites Profile at the Early Stage of Breast Cancer in Rats

The cytotoxic properties of zinc nanoparticles have been evaluated in vitro against several types of cancer. However, there is a lack of significant evidence of their activity in vivo, and a potential therapeutic application remains limited. Herein we report the effective inhibition of tumor growth by zinc nanoparticles in vivo, as the effect of the dietary intervention, after the chemical induction in a rodent model of breast cancer. Biopsy images indicated grade 1 tumors with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, a moderately differentiated grade 2 adenocarcinoma was identified. Moreover, after the supplementation with zinc nanoparticles, the levels of several metabolites associated with cancer metabolism, important to its survival, were found to have been altered. We also revealed that the biological activity of zinc in vivo depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression

Alterations in Blood Plasma Metabolome of Patients with Lesniowski-Crohn’s Disease Shortly after Surgical Treatment—Pilot Study

Lesniowski-Crohn’s disease (CD) is a type of chronic inflammatory bowel disease (IBD) of uncertain etiology. Initially, pharmacological management is undertaken; however, surgical intervention is necessary to improve life quality and relieve symptoms in most cases. Here changes are reported in blood metabolome that occurred three days after the ileo-colic region resection in the case of seven patients. Alterations are observed in levels of metabolites associated with multiple mitochondrial pathways, based on the Metabolite Set Enrichment Analysis, reflecting a high energy demand in the post-operative period. As most of these metabolites are also essential nutrients supplied from foods, we believe that our results might contribute to the discussion on perioperative nutrition’s role in enhanced recovery

Relationship between Excreted Uremic Toxins and Degree of Disorder of Children with ASD

Autism spectrum disorder (ASD) is a complex developmental disorder in which communication and behavior are affected. A number of studies have investigated potential biomarkers, including uremic toxins. The aim of our study was to determine uremic toxins in the urine of children with ASD (143) and compare the results with healthy children (48). Uremic toxins were determined with a validated high-performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) method. We observed higher levels of p-cresyl sulphate (pCS) and indoxyl sulphate (IS) in the ASD group compared to the controls. Moreover, the toxin levels of trimethylamine N-oxide (TMAO), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were lower in ASD patients. Similarly, for pCS and IS in children classified, according to the intensity of their symptoms, into mild, moderate, and severe, elevated levels of these compounds were observed. For mild severity of the disorder, elevated levels of TMAO and comparable levels of SDMA and ADMA for ASD children as compared to the controls were observed in the urine. For moderate severity of ASD, significantly elevated levels of TMAO but reduced levels of SDMA and ADMA were observed in the urine of ASD children as compared to the controls. When the results obtained for severe ASD severity were considered, reduced levels of TMAO and comparable levels of SDMA and ADMA were observed in ASD children