CXCL1, RANTES, IFN-γ, and TMAO as Differential Biomarkers Associated with Cognitive Change After an Anti-Inflammatory Diet in Children with ASD and Neurotypical Peers.

Researchers studied whether an anti-inflammatory diet affects autistic and non-autistic children differently. After 12 weeks, autistic children showed reduced inflammation markers in their blood and improvements in learning, attention, and thinking skills. Non-autistic children had smaller improvements and minimal biological changes. This suggests anti-inflammatory diets may work differently for autistic children by reducing inflammation and improving brain function.

This study examined whether a 12-week anti-inflammatory diet produces different biological and cognitive responses in autistic children compared to neurotypical peers. Twenty-two children (11 with ASD, 6 neurotypical on diet, 5 neurotypical controls) completed assessments of immune markers and cognitive testing. Results showed that autistic children experienced significant reductions in inflammatory markers (IFN-γ, RANTES, CXCL1) and TMAO, which were associated with improvements in verbal learning, attention, and executive function. Neurotypical children showed modest cognitive gains with minimal biological changes.

The findings suggest anti-inflammatory diets may have ASD-specific effects on immune-metabolic pathways that relate to cognitive improvements, supporting personalized nutrition approaches.

Findings support exploring anti-inflammatory diets as complementary intervention for autism, particularly for cognitive domains. Biomarkers like CXCL1, RANTES, and TMAO may help identify children most likely to benefit. Results suggest need for ASD-specific nutrition approaches rather than one-size-fits-all dietary interventions.

Very small sample size (11 ASD, 6 NT-diet, 5 controls) limits generalizability. No mention of randomization or blinding. Short 12-week duration may not capture long-term effects. Unclear baseline characteristics and dietary compliance measures.

: Neuroimmune and metabolic dysregulation have been increasingly implicated in the cognitive heterogeneity of autism spectrum disorder (ASD). However, it remains unclear whether anti-inflammatory diets engage distinct biological and cognitive pathways in autistic and neurotypical children. This study examined whether a 12-week anti-inflammatory dietary protocol produces group-specific neuroimmune-metabolic signatures and cognitive responses in autistic children, neurotypical children receiving the same diet, and untreated neurotypical controls.: Twenty-two children (11 with ASD, six a on neurotypical diet [NT-diet], and five neurotypical controls [NT-control]) completed pre-post assessments of plasma IFN-γ, CXCL1, RANTES (CCL5), trimethylamine-N-oxide (TMAO), and an extensive ENI-2/WISC-IV neuropsychological battery. Linear mixed-effects models were used to test the Time × Group effects on biomarkers and cognitive domains, adjusting for age, sex, and baseline TMAO.

Bayesian estimation quantified individual changes (posterior means, 95% credible intervals, and posterior probabilities). Immune-cognitive coupling was explored using Δ-Δ correlation matrices, network metrics (node strength, degree centrality), exploratory mediation models, and responder (≥0.5 SD domain improvement) versus non-responder analyses.: In ASD, the diet induced robust reductions in IFN-γ, RANTES, CXCL1, and TMAO, with decisive Bayesian evidence for IFN-γ and RANTES suppression (posterior P(δ < 0) > 0.99). These shifts were selectively associated with gains in verbal learning, semantic fluency, verbal reasoning, attention, and visuoconstructive abilities, whereas working memory and executive flexibility changes were heterogeneous, revealing executive vulnerability in individuals with smaller TMAO reductions. NT-diet children showed modest but consistent improvements in visuospatial processing, attention, and processing speed, with minimal biomarker changes; NT controls remained biologically and cognitively stable.

Network analyses in ASD revealed a dense chemokine-anchored architecture with CXCL1 and RANTES as central hubs linking biomarker reductions to improvements in fluency, memory, attention, and executive flexibility. ΔTMAO predicted changes in executive flexibility only in ASD (explaining >50% of the variance), functioning as a metabolic node of executive susceptibility. Responders displayed larger coordinated decreases in all biomarkers and broader cognitive gains compared to non-responders.: A structured anti-inflammatory diet elicits an ASD-specific, coordinated neuroimmune-metabolic response in which suppression of CXCL1 and RANTES and modulation of TMAO are tightly coupled with selective improvements in verbal, attentional, and executive domains. Neurotypical children exhibit modest metabolism-linked cognitive benefits and minimal immune modulation. These findings support a precision-nutrition framework in ASD, emphasizing baseline immunometabolic profiling and network-level biomarkers (CXCL1, RANTES, TMAO) to stratify responders and design combinatorial interventions targeting neuroimmune-metabolic pathways.