An Overview on Fecal Profiles of Amino Acids and Related Amino-Derived Compounds in Children with Autism Spectrum Disorder in Tunisia

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by the impairment of social interaction, difficulties in communication, and repetitive behaviors. Alterations in the metabolism of amino acids have been reported. We performed a chromatographic analysis of fecal amino acids, ammonium, biogenic amines, and gamma aminobutyric acid (GABA) in Tunisian autistic children from 4 to 10 years, and results were compared with their siblings (SIB) and children from the general population (GP). ASD presented significantly higher levels of fecal amino acids than SIB and GP; differences being more pronounced in younger (4-7 years) than in older (8-10 years) individuals whereas no changes were found for the remaining compounds. Lower levels of histidine were the only difference related with severe symptoms of autism (CARS scale). A linear discriminant analysis (LDA) based on fecal amino acid profiles clearly separated ASD, SIB, and GP at 4 to 7 years but not at more advanced age (8-10 years), evidencing more pronounced alterations in younger children. The relationship of fecal amino acids with autism needs deeper research integrating blood analytical parameters, brain metabolism, and intestinal microbiota. Fecal amino acids could be targeted for designing personalized diets to prevent or minimize cognitive impairments associated with ASD.

Keywords: GABA; alanine; amino acids; autism; biogenic amines; feces; glutamate; neurotransmitters.

Figure 1

Fecal levels of amino acids in samples from autistic children (ASD), their siblings (SIB), and children from the general population (GP) in Tunisia. Asp: aspartate; Glu: glutamate; Ser: serine; Asn: asparagine; Gln: glutamine; His: histidine; Gly: glycine; Thr: threonine; Arg: arginine; Ala: alanine; Tyr: tyrosine; Val: valine; Met: methionine; Trp: tryptophan; Ile: Isoleucine; Leu: leucine: Phe: phenylalanine; Orn: Ornithine; Lys: lysine. Bars represent mean values and horizontal lines on the bars represent standard deviation. Different letters (a, b, ab, c) indicate significant differences among groups of children for each amino acid (p < 0.05).

Figure 2

Fecal levels of amino acids in samples from autistic children (ASD), their siblings (SIB), and children from the general population (GP) in Tunisia stratified by age: (A) 4–7 years, (B) 8–10 years. Asp: aspartate; Glu: glutamate; Ser: serine; Asn: asparagine; Gln: glutamine; His: histidine; Gly: glycine; Thr: threonine; Arg: arginine; Ala: alanine; Tyr: tyrosine; Val: valine; Met: methionine; Trp: tryptophan; Ile: Isoleucine; Leu: leucine: Phe: phenylalanine; Orn: Ornithine; Lys: lysine. Bars represent mean values and horizontal lines on the bars represent standard deviation. Different letters (a, b, ab) indicate significant differences among groups of children for each amino acid (p < 0.05).

Figure 2

Fecal levels of amino acids in samples from autistic children (ASD), their siblings (SIB), and children from the general population (GP) in Tunisia stratified by age: (A) 4–7 years, (B) 8–10 years. Asp: aspartate; Glu: glutamate; Ser: serine; Asn: asparagine; Gln: glutamine; His: histidine; Gly: glycine; Thr: threonine; Arg: arginine; Ala: alanine; Tyr: tyrosine; Val: valine; Met: methionine; Trp: tryptophan; Ile: Isoleucine; Leu: leucine: Phe: phenylalanine; Orn: Ornithine; Lys: lysine. Bars represent mean values and horizontal lines on the bars represent standard deviation. Different letters (a, b, ab) indicate significant differences among groups of children for each amino acid (p < 0.05).

Figure 3

Fecal levels of amino acids in samples from autistic children (ASD), stratified by severity of the disease according to CARS score: mild to moderate (30–36) and severe (37–60). Asp: aspartate; Glu: glutamate; Ser: serine; Asn: asparagine; Gln: glutamine; His: histidine; Gly: glycine; Thr: threonine; Arg: arginine; Ala: alanine; Tyr: tyrosine; Val: valine; Met: methionine; Trp: tryptophan; Ile: Isoleucine; Leu: leucine: Phe: phenylalanine; Orn: Ornithine; Lys: lysine. Bars represent mean values and horizontal lines on the bars represent standard deviation. Different letters (a, b) indicate significant differences between groups of children for each amino acid (p < 0.05).

Figure 4

Projection of the metabolic profiles of the three groups of children stratified by age (4–7 years, and 8–10 years) into the plane formed by the two classification functions (F1 and F2) obtained from the linear discriminant analysis based on fecal levels of 19 protein amino acids excluding proline and cysteine and including the non-protein amino acid ornithine. Blue spots represent autistic children: ASD; green spots represent individuals from the general population (GP); purple spots represent the siblings from autistic children (SIB): Oval lines around individual spots are arbitrarily representing groups based on the profile of compounds analyzed. Centroids are indicated with rhomboid shapes. Percentage of variance explained by each of the two functions is indicated within parentheses in each axis.