Role of mycotoxins in the pathobiology of autism: A first evidence.

ABSTRACT

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.