Urinary p-Cresol in ASD

The etiology of autism encompasses a broad range of causative events, ranging from rare de novo high-penetrance mutations affecting genes such as NLGN3/4, SHANK3, NRXN1, and MECP2, to a complex mix of environmental and epigenetic factors acting upon a vulnerable genetic background. Increasing prevalence rates, decreasing heritability estimates, polygenic models with multiple incompletely penetrant de novo mutations, all suggest that, in addition to broader diagnostic criteria and increased awareness, also a real increase in incidence primarily due to greater gene-environment interactions may also be occurring. Notably, the phenotypic heterogeneity of ASD suggests the existence of many “autisms”, each characterized by specific etiopathogenetic underpinnings. Given the complex nature of this disorder, great effort is now underway aiming to define a reliable panel of biological markers able to assist clinicians in an early diagnosis. P-cresol (4-methylphenol) belongs to the cresol class of organic aromatic compounds. Environmental p-cresol is absorbed through the gastrointestinal and the respiratory tracts, as well as through the intact skin. Physiological sources of p-cresol are represented by some gut bacteria which express synthetic enzymes not found in human cells. Urinary p-cresol or its conjugated derivative p-cresylsulfate hold the promise of representing one of these biomarkers in small autistic children and could contribute to identify a subgroup of ASD children characterized by greater severity, to better delineate abnormal gut function in autism and perhaps the entire pathophysiology of the disease in at least some individuals.