Rescue of social deficits by early-life melatonin supplementation through modulation of gut microbiota in a murine model of autism.

Scientists tested whether giving melatonin (a natural hormone) to pregnant mice and newborn pups could help with autism-like behaviors. They used a chemical called VPA to create autism symptoms in mice. The melatonin improved social behaviors in the mice pups. The researchers found this worked by fixing problems with gut bacteria, especially increasing helpful bacteria called Akkermansia. This is early research in mice, not humans.

This preclinical study investigated melatonin supplementation during early development in a mouse model of autism. Researchers used valproic acid (VPA) to induce autism-like behaviors in mice, then examined whether melatonin given during late pregnancy and early postnatal period could improve social deficits. The study found that early-life melatonin supplementation rescued social behavioral deficits in the autism model mice. The mechanism appeared to involve restoration of gut microbiota, particularly increasing Akkermansia bacteria.

Direct supplementation with Akkermansia also improved social behaviors by activating dopaminergic neurons in the brain's reward center. These findings suggest a novel pathway linking gut microbiota to social behavior regulation in autism models.

Provides preclinical evidence for early-life melatonin and gut microbiota interventions in autism. Suggests critical developmental windows for intervention. Identifies Akkermansia as potential therapeutic target. Human studies needed before clinical application.

Animal model study only - findings may not translate to humans. Sample size not reported. Single autism model used (VPA-induced). Mechanism studies preliminary. Long-term effects unknown.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a rapidly increasing global prevalence. Early unstable and immature microbiota are often observed in ASD patients, resulting in neurobehavioral dysfunction. Since the establishment of stable gut microbiota in early life falls into the same critical time window as neurodevelopment, manipulations of the gut microbiota during early life could become a promising strategy for ASD. Melatonin is an endogenous hormone and can restore gut microbial dysbiosis under various disease conditions.

Here, we explored the effects of melatonin supplementation during early life on the gut microbiota of the offspring and the subsequent impact on ASD-associated behaviors. Using the valproic acid (VPA) - induced mouse model of autism, we found that melatonin supplementation during late gestation and early postnatal development rescued the social deficits of the offspring. In addition, melatonin restored gut microbial dysbiosis in the VPA-exposed offspring, which was characterized by the significant upregulation of Akkermansia spp. Furthermore, supplementation of Akkermansia spp. alleviated the social deficits induced by VPA exposure via activating the dopaminergic neurons in the ventral tegmental area.

These findings discover a novel mechanism underlying the gut microbiota regulation of social behaviors and provide the biological basis for developing gut microbiota-based therapeutics for ASD.