Anti-Inflammatory Diet and Probiotic Supplementation as Strategies to Modulate Immune Dysregulation in Autism Spectrum Disorder

<b>Background/Objectives</b>: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with behavioral and cognitive impairments. Increasing evidence also links ASD with systemic immune dysregulation, including abnormal cytokine profiles and chronic low-grade inflammation. Emerging evidence suggests that targeted dietary strategies and probiotic supplementation may modulate immune responses and gut-brain interactions in patients with ASD. This study aimed to evaluate the immunomodulatory effects of a structured anti-inflammatory diet (<i>NeuroGutPlus</i>) compared to multi-strain probiotics in children with ASD. <i>NeuroGutPlus</i> is a nutritionally complete anti-inflammatory dietary protocol that targets gut integrity, inflammation, and mitochondrial function. It includes a diet low in gluten, FODMAPs, casein, and artificial additives, and a high intake of omega-3 fatty acids, polyphenols, and fermentable fibers. <b>Methods</b>: A total of 30 children with ASD and 12 neurotypical controls were enrolled in a 12-week randomized controlled nutritional trial. Participants received either a <i>NeuroGutPlus</i> anti-inflammatory diet, probiotic supplementation (16 strains of <i>Lactobacillus</i> and Bifidobacterium), or no intervention. Plasma levels of 20 cytokines and chemokines were measured pre- and post-intervention using multiplex Luminex immunoassays. Principal component analysis (PCA) was used to explore shifts in the immune profile. <b>Results</b>: Patients treated with the <i>NeuroGutPlus</i> diet significantly reduced IFN-γ levels (<i>p</i> = 0.0090) and showed a stabilizing effect on immune profiles, as evidenced by PCA clustering. Probiotic supplementation led to a significant increase in IL-8 (+66.6 pg/mL; <i>p</i> = 0.0350) and MIP-1β (+74.5 pg/mL; <i>p</i> = 0.0100), along with a decrease in IFN-γ (<i>p</i> = 0.0070), suggesting reconfiguration of innate immune responses. Eight out of eleven biomarkers showed significant post-intervention differences between groups, indicating distinct immunological effects. <b>Conclusions</b>: This study provides evidence that anti-inflammatory diets exert broader and more consistent immunoregulatory effects than probiotics alone in children with ASD. These findings support the inclusion of precision dietary strategies as non-pharmacological interventions to mitigate immune-related dysfunction in patients with ASD.