3-(3-Hydroxyphenyl)-3-hydroxypropanoic acid (HPHPA) is an organic acid detected in human urine. It is relatively abundant in adult human urine and it is normally relatively benign. It is thought that the presence of this acid is from nutritional sources (i.e. dietary phenylalanine or polyphenols). However, there has been a considerable degree of ambiguity in the origin and/or significance of this compound (PMID:11978597). Recently, it has been reported that HPHPA is actually an abnormal phenylalanine metabolite arising from bacterial metabolism in the gastrointestinal tract. Specifically, HPHPA appears to arise from the action of the anaerobic bacteria Clostridia sp. (PMID:20423563; PMID:24063620). Elevated levels of HPHPA have been reported in the urine of children with autism as well as in adult patients with schizophrenia. It has been proposed that HPHPA may be a bacterial metabolite of m-tyrosine, a tyrosine analog that causes symptoms of autism in experimental animals. Under certain conditions, HPHPA can act as a neurotoxin and a metabotoxin. A neurotoxin causes damage to nerve cells and nerve tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of HPHPA are associated with autism and schizophrenia. The mechanism by which HPHPA exerts its toxic effects is not clear.  It may function as a catecholamine analog and disrupt catecholamine signalling, especially in younger individuals. Alternately, HPHPA may function as an amino acid analog to tyrosine and phenylalanine.  High plasma concentrations of phenylalanine (and possibly HPHPA) are known to influence the blood-brain barrier transport of large neutral amino acids. This altered transport is believed to interfere with the function of different cerebral enzyme systems in the developing brain. Studies have shown that higher levels of HPHPA are associated with overgrowth of Clostridia in the gut, including Clostridium difficile, Clostridium sporogenes, Clostridium botulinum, Clostridium calortolerans, Clostridium mangenoyi, Clostridium ghoni, Clostridium bifermentans, Clostridium sordelli. (PMID:20423563; PMID:24063620)