Metabolic differences underlying two distinct rat urinary phenotypes, a suggested role for gut microbial metabolism of phenylalanine and a possible connection to autism

► This article explores the origin of two distinct rat urinary compositional phenotypes. ► An hypothesis is presented that involves gut microbial metabolism of phenylalanine. ► Specific metabolic conversions and pathways are discussed. ► Possible connections to postulated biomarkers for autism are highlighted. A novel explanation is proposed for the metabolic differences underlying two distinct rat urinary compositional phenotypes i.e. that these may arise from differences in the gut microbially-mediated metabolism of phenylalanine. As part of this hypothesis, it is further suggested that elements of the mammalian gut microbiota may convert phenylalanine to cinnamic acid, either by means of an ammonia lyase-type reaction or by means of a three step route via phenylpyruvate and phenyllactate. The wider significance of such conversions is discussed with similar metabolism of tryptophan and subsequent glycine conjugation potentially explaining the origin of trans-indolylacryloylglycine, a postulated marker for autism.