Autism spectrum disorders and nutritional interventions: dimethylglycine and B-vitamins effects on behaviour, inflammation, microbiota and mitochondria in liver and brain synapses.

Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions with a multifactorial etiology, where genetic and environmental interactions lead to cellular dysfunctions in the brain and peripheral tissues, associated with dysbiosis, inflammation, oxidative stress, and mitochondrial impairment. Emerging evidence highlights the critical role of the gut microbiota in the metabolic and neuroinflammatory imbalances observed in ASD. In this context, the liver plays a pivotal metabolic role, being closely connected to the gut and brain through metabolic pathways, influencing overall health. Since nutritional interventions and bioactive food compounds are key modulators of these processes, this study aims to investigate the effects of dietary supplementation with dimethylglycine and B group vitamins on the metabolic and inflammatory state of BTBR mice, a well-established model of ASD, focusing on the gut-liver-brain axis. Our findings indicate that dimethylglycine and B group vitamins administration in BTBR mice mitigates ASD-like behaviors. This beneficial effect may be the result of multiple mechanisms as decrease in oxidative stress and inflammatory state, modulation of gut microbiota and body composition, reduced hepatic steatosis, and improved mitochondria functions in liver, brain cortex and synaptic areas. These results suggest that dietary supplementation with dimethylglycine and B vitamins can positively modulate the gut-liver-brain axis in ASD, offering new insights into metabolic and neuroinflammatory interventions.