Alterations of the Intestinal Permeability are Reflected by Changes in the Urine Metabolome of Young Autistic Children: Preliminary Results

Abstract

Several metabolomics-based studies have provided evidence that autistic subjects might share metabolic abnormalities with gut microbiota dysbiosis and alterations in gut mucosal permeability. Our aims were to explore the most relevant metabolic perturbations in a group of autistic children, compared with their healthy siblings, and to investigate whether the increased intestinal permeability may be mirrored by specific metabolic perturbations. We enrolled 13 autistic children and 14 unaffected siblings aged 2–12 years; the evaluation of the intestinal permeability was estimated by the lactulose:mannitol test. The urine metabolome was investigated by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The lactulose:mannitol test unveiled two autistic children with altered intestinal permeability. Nine metabolites significantly discriminated the urine metabolome of autistic children from that of their unaffected siblings; however, in the autistic children with increased permeability, four additional metabolites—namely, fucose, phenylacetylglycine, nicotinurate, and 1-methyl-nicotinamide, strongly discriminated their urine metabolome from that of the remaining autistic children. Our preliminary data suggest the presence of a specific urine metabolic profile associated with the increase in intestinal permeability.

NAD+ Precursors and Intestinal Inflammation: Therapeutic Insights Involving Gut Microbiota

“…In this study, elevated levels of urinary nicotinurate and 1-methyl-NAM in ASD children with increased gut permeability revealed disruptions in the tryptophan-NA metabolic pathway, whereas the presence of these catabolites in the urine indicated a shift in tryptophan metabolism from serotonin biosynthesis to the formation of NA [88]. It has been proposed that, in children with ASD, the high level of urinary 1-methyl-nicotinamide could reflect an increased demand for NA [88,118].…”

“…Remarkably, gastrointestinal issues, such as chronic diarrhea, constipation, irritable bowel syndrome, and gastroesophageal reflux are common comorbidities in ASD, likely arising from a vicious cycle that involves intestinal dysbiosis, intestinal mucosa inflammation and increased intestinal permeability compounded by food selectivity [88]. In this study, elevated levels of urinary nicotinurate and 1-methyl-NAM in ASD children with increased gut permeability revealed disruptions in the tryptophan-NA metabolic pathway, whereas the presence of these catabolites in the urine indicated a shift in tryptophan metabolism from serotonin biosynthesis to the formation of NA [88]. It has been proposed that, in children with ASD, the high level of urinary 1-methyl-nicotinamide could reflect an increased demand for NA [88,118].…”

Intestinal Barrier Dysfunction and Microbiota–Gut–Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder

“…On this subject, in recent years, the emergence of metabolomics has made it possible to detect alterations in metabolites in ASD effectively [ 148 ], and major metabolomic studies on blood samples are summarized in Table 1 . Decreased levels of antioxidants, high levels of bacterial-derived phenolic compounds and a high concentration of SCFAs have been reported to be found in the urine, stools and blood of children with autism [ 149 , 150 , 151 , 152 ].…”

Physical Activity, Gut Microbiota, and Genetic Background for Children and Adolescents with Autism Spectrum Disorder

“…In addition, a subset of ASD children with increased gut permeability were identified using the lactulose:mannitol test. In these children, four additional gut-permeable metabolites (phenylacetyl glycine, fucose, nicotinurate, and 1-methyl-nicotinamide) were found in their urine, which were not seen in the urine of the remaining children with ASD [ 167 ]. In another urinary metabolomic study, the authors identified significant dysregulation to the purine, tyrosine, phenylalanine and tryptophan pathways, characterized by increased phenylalanine and decreased tyrosine levels.…”