Urinary p-cresol in autism spectrum disorder.
“These are not trivial levels,” Persico says — in fact, they’re similar to levels seen in patients with kidney failure. “P-cresol is pretty nasty stuff.” 2010 commentary (see Further Reading)
Child and Adolescent NeuroPsychiatry Unit, University “Campus Bio-Medico”, Rome, Italy; Dept. of Experimental Neurosciences, IRCCS “Fondazione Santa Lucia”, Rome, Italy. Electronic address: firstname.lastname@example.org.
Autism spectrum disorder (ASD) is a neuropsychiatric disorder with onset during early childhood and life-long consequences in most cases. It is characterized by impairment in social interaction and communication, as well as by restricted patterns of interest and stereotyped behaviors.
The etiology of autism is highly heterogeneous, encompassing a large range of genetic and environmental factors. Several lines of evidence 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.
Environmental exposure to the organic aromatic compound p-cresol (4-methylphenol) is relatively common and occurs through the skin, as well as the gastrointestinal and respiratory systems. However, the largest and most widespread source of this compound is represented by some gut bacteria which express p-cresol synthesizing enzymes not found in human cells.
Urinary p-cresol and its conjugated derivative p-cresylsulfate have been found elevated in an initial sample and recently in a replica sample of autistic children below 8years of age, where it is associated with female sex, greater clinical severity regardless of sex, and history of behavioral regression. Potential sources of p-cresol excess in ASD, such as gut infection, chronic constipation, antibiotics, abnormal intestinal permeability, and environmental exposure, are being investigated.
P-cresol may contribute to worsen autism severity and gut dysfunction, often present in autistic children. It may also contribute to a multibiomarker diagnostic panel useful in small* autistic children.
* Younger ? see study below
Urinary p-cresol is elevated in small children with severe autism spectrum disorder.
Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Via Alvaro del Portillo 21, Rome, Italy.
Several studies have described in autistic patients an overgrowth of unusual gut bacterial strains, able to push the fermentation of tyrosine up to the formation of p-cresol.
We compared levels of urinary p-cresol, measured by high-performance liquid chromatography-ultraviolet, in 59 matched case-control pairs. Urinary p-cresol was significantly elevated in autistic children smaller * than 8 years of age (p < 0.01), typically females (p < 0.05), and more severely affected regardless of sex (p < 0.05). Urinary cotinine measurements excluded smoking-related hydrocarbon contaminations as contributors to these differences.
Hence, elevated urinary p-cresol may serve as a biomarker of autism liability in small children, especially females and more severely affected males.
Potential biomarker found in urine of children with autism
Young children with autism have high urine levels of a compound that is likely to be a product of gut bacteria, according to a poster presented Tuesday at the Society for Neuroscience annual meeting.
The compound, P-cresol, “can in no way be produced by human metabolism,” says study leader Antonio Persico, associate professor of physiology at the University Campus Bio-Medico in Rome. Only certain species of bacteria — particularly Clostridium difficile, which is found in the gut but can be harmful at high levels — have the enzyme necessary to make the chemical.
A 2005 study found that children with autism are more likely to have higher levels of Clostridium bacteria in the gut compared with healthy children.
In the new study, Persico’s team analyzed urine samples from 59 children with autism and 59 controls. They found that among children age 7 and younger, about 28 percent of those with autism have urine P-cresol-levels of above 150 micrograms per milliliter, a concentration not seen in any children in the control group.
“These are not trivial levels,” Persico says — in fact, they’re similar to levels seen in patients with kidney failure. “P-cresol is pretty nasty stuff.”
P-cresol is chemically similar to phenol, a corrosive compound. Animal studies also show that it is toxic, perhaps acting by interfering with mitochondria, the centers of cellular energy production and metabolism.
Puzzlingly, the difference in urine P-cresol disappears in older children — among those 8 and older, children with autism have the same levels as do controls. “We have no data at this point to explain this finding,” Persico says.