Metabolomics of autism spectrum disorders: early insights regarding mammalian-microbial cometabolites

Abstract

We overhauled the value of either targeted or untargeted metabolomics studies in autism for identifying the most relevant metabolic pathways and key metabolites implicated in the disease, with special emphasis to mammalian-microbial metabolites. The most discriminant metabolites in ASD belong to amino acid metabolism, antioxidant status, nicotinic acid metabolism, and mitochondrial metabolism. Expert commentary: Most published studies point out the role of metabolites derived from the gut microbiota: they can modulate the behavioral phenotype of the autistic children, greatly influencing host metabolic pathways and the immune system, shaping the individual susceptibility to the disease. Pitfalls and caveats in metabolomics results across studies have been additionally recognized and discussed leading to the conclusion that metabolomics studies in ASD are far to be definitive and univocal.

How could metabolomics change pediatric health?

“…In particular, the metabolites mostly associated to ASD seems those involved in amino acid metabolism, cholesterol metabolism, folate abnormalities, antioxidant status, nicotinic acid metabolism, and mitochondrial metabolism. A great role could also be played by some metabolites derived from the gut microbiota, potentially shaping ADS children behavior, metabolic patterns and immune response [105][106][107][108], tryptophan, vitamin B6, purine metabolic pathways, phenylalanine and tyrosine biosynthesis, intermediary compounds of the TCA cycle [108].…”

Genetics and epigenetics of autism: A Review

“…Using a few genetic polymorphisms (folate hydrolase 1 or GCPII C1561T, serine hydroxymethyltransferase 1 C1420T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and 5‐methyltetrahydrofolate‐HCy methyltransferase reductase A66G) as well as hyperhomocysteinemia as risk factors, an artificial neural network model has been developed as a moderate predictor of autism risk . Metabolomics studies of autism that aim at identifying metabolic pathways that are disrupted in autistic children have been carried out, and some studies have pointed out that elevated levels of nicotinic acid, which needs methylation by S‐adenosylmethionine, and the elevation of nicotinic acid would pose a challenge for the already low methylation status of autistic subjects, leading to problems with oxidative stress . Some studies have also pointed out the role of metabolites derived from the gut microbiota .…”

“…74 Metabolomics studies of autism that aim at identifying metabolic pathways that are disrupted in autistic children have been carried out, and some studies have pointed out that elevated levels of nicotinic acid, which needs methylation by S-adenosylmethionine, and the elevation of nicotinic acid would pose a challenge for the already low methylation status of autistic subjects, leading to problems with oxidative stress. 81 Some studies have also pointed out the role of metabolites derived from the gut microbiota. [82][83][84][85] However, overall the conclusion is that metabolomics studies in ASD are thus far not definitive or univocal.…”

Microbiota changes associated with ADNP deficiencies: rapid indicators for NAP (CP201) treatment of the ADNP syndrome and beyond

“…In addition, children diagnosed with ASD display various medical comorbidities of high prevalence (Banaschewski et al 2011;Geier et al 2012;Ozsivadjian et al 2013). For example, previous research strongly implicates a role for metabolites derived from the gut microbiota as modulators of autistic behavioral phenotypes, influencing the host metabolome and shaping disease outcomes, at the individual level (Mussap et al 2016).…”