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Objectives: Gene-environment interaction is an emerging hypothesis to expound not only the autism pathogenesis but also the increased incidence of neurodevelopmental disorders (such as autistic spectrum disorder, attention-deficit, hyperactivity disorder). Among xenobiotics, mycotoxins are worldwide contaminants of food that provoke toxicological effects, crucially resembling several symptoms associated with autism such as oxidative stress, intestinal permeability, and inflammation. Here, we focused on a group of mycotoxins to test their role in the manifestation of autism, try to explain their mechanism of action, and discuss possible preventive and therapeutic interventions. Methods: Autistic children (n = 52) and healthy children [n = 58 (31 siblings and 27 unrelated subjects)] were recruited and body fluids and clinical data collected. The diagnosis of autism was made according to DSM V criteria, then with GMDS 0-2, WPPSI, and ADOS. Ochratoxin A (OTA), gliotoxin, zearalenone, and sphingosine/sphinganine ratio were determined by LC analysis in sera and urines. Statistical analysis was performed by the Wilcoxon Rank Sum (Mann-Whitney) test and Spearman test. Results: By comparing the results of autistic patients with those of unrelated controls, a significant association was found for OTA levels in urines (P = 0.0002) and sera (P = 0.0017), and also comparing patients with siblings and unrelated controls together (P = 0.0081). Discussion: Our results are the first describing a possible role of OTA in the pathobiology of autism. Recalling the male prevalence of ASD (male/female = 4-5/1), it is noted that, in animal models, OTA exerts its neurotoxicity especially in males. Moreover, in vitro, OTA increases microRNA-132 that is dysregulated in autistic patients and involved in reciprocal regulation of the autism-related genes MeCP2 and PTEN. A personalized diet coupled with probiotic administration, especially OTA adsorbing Lactobacillus, could ameliorate autistic symptoms in OTA-positive patients. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a Fusarium toxin, to which humans are frequently exposed via diet. Although the elderly are speculated to be sensitive to the toxic effects of DON as a result of age-related conditions, disease and altered DON metabolism, there is lack of available data on DON biomarkers in this age group. This study characterised urinary DON concentrations and its metabolites in elderly aged ≥65years (n = 20) residing in Hull, UK. Morning urinary specimens were collected over two consecutive days together with food records to assess dietary intake over a 24h-period prior to each urinary collection. Free DON (un-metabolised), total DON (sum of free DON and DON-glucuronides or DON-GlcA) and de-epoxy deoxynivalenol (DOM-1) were analysed using a validated LC-MS/MS methodology. Total DON above the limit of quantification 0.25 ng/mL was detected in the urine from 90% of elderly men and women on both days. Mean total DON concentrations on day 1 were not different from those on day 2 (elderly men, day 1: 22.2 ± 26.3 ng/mg creatinine (creat), day 2: 28.0 ± 34.4 ng/mg creat, p = 0.95; elderly women, day 1: 22.4 ± 14.6 ng/mg creat, day 2: 29.1 ± 22.8 ng/mg creat, p = 0.58). Free DON and DON-GlcA were detected in 60-70% and 90% of total urine samples, respectively. DOM-1 was absent from all samples; the LoQ for DOM-1 was 0.50 ng/mL. Estimated dietary intake of DON suggested that 10% of the elderly exceeded the maximum provisional tolerable daily intake for DON. In this single-site, UK-based cohort, elderly were frequently exposed to DON, although mean total DON concentrations were reported at moderate levels. Future larger studies are required to investigate DON exposure in elderly from different regions of the UK, but also from different counties worldwide. [ABSTRACT FROM AUTHOR]