Abstract
BACKGROUND: Due to the variability in clinical manifestations and the frequent diagnostic delays associated with autism spectrum disorder (ASD), interest in identifying fatty acids as potential biomarkers is increasing. Nonetheless, owing to inconclusive evidence, further investigation is needed. OBJECTIVE: To explore the relationship between fatty acids and ASD risk and identify distinct fatty acid metabolites in children with ASD. METHODS: Plasma fatty acid levels were tested in totally 131 participants (ages 2-6 and male-to-female ratio 2.5:1) with and without ASD using gas chromatography coupled to flame ionization detector and mass spectrometer (GC-FID/MS) technology. Between-group differences in each fatty acid and the omega-3 polyunsaturated fatty acid/arachidonic acid (AA) ratio were explored. We adjusted for covariates via multivariable models. The discriminatory sensitivity of meaningful fatty acids between ASD and control groups was assessed via receiver operating characteristic curve (ROC) analysis. RESULTS: Two of 22 fatty acids significantly differed between children with ASD and typically developing children. Specifically, C20:4ω6 (AA) (457.4 ± 195.3 μmol/L vs. 493.3 ± 111.9 umol/L, P = 0.044) and C24:0 (34.7 ± 7.9 μmol/L vs. 38.3 ± 8.7 μmol/L, P = 0.019) levels were significantly lower in the autism group than in the control group, whereas the alpha-linolenic acid (ALA)/AA ratio [0.13(0.10, 0.18) vs. 0.10(0.08, 0.15)] was significantly greater in children with autism than in those without. Potential interactive effects between AA, C24:0, ALA/AA and gastrointestinal syndromes were further observed. Biomarkers were assessed via ROC analysis, which revealed AA, C24:0 and ALA/AA AUC values of 0.60(0.50~0.70), 0.62(0.52~0.72) and 0.62 (0.52~0.71), respectively. CONCLUSIONS: Fatty acid disturbance was observed among children with ASD, particularly in terms of AA, C24:0 and the ALA/AA ratio. These findings provide valuable insights into the underlying mechanisms of ASD and suggest that modulating fatty acid levels could serve as an intervention strategy.