Pharmacological researchFeb 22, 2026

Semaglutide reduces autism-like behaviors in BTBR mice by changing gut bacteria

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 23, 2026

Abstract

Semaglutide treatment during early neurodevelopment significantly improves social behavior and cognitive function in BTBR mice.

Significant improvements in social behavior, cognitive function, and repetitive behaviors were observed in BTBR mice following semaglutide administration.
The therapeutic effect of semaglutide is linked to the restoration of gut microbiota, as shown by fecal microbiota transplantation.
Lower levels of adrenic acid (AdA) in BTBR mice returned to normal after semaglutide treatment, indicating its role as a mediator.
Hippocampal neurogenesis was associated with semaglutide treatment, and AdA supplementation also restored social behaviors and neurogenesis.
Findings suggest the gut microbiota-brain axis is critical for the effects of semaglutide on autism spectrum disorder.

Simplified

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental condition characterized by deficits in social communication and the presence of repetitive behaviors. The significance of the gut-brain axis in the pathogenesis of ASD often points to a relationship with gut dysbiosis and metabolic disruptions in affected individuals. This study investigates the potential of the glucagon-like peptide-1 receptor agonist, semaglutide, to modulate gut microbiota, metabolic pathways, and neurodevelopmental outcomes using the BTBR T(+) Itpr3(tf)/J (BTBR) mouse model of ASD. Our findings indicate that administration of semaglutide during an early neurodevelopmental stage leads to significant improvements in social behavior, cognitive function, and repetitive behaviors in BTBR mice. This therapeutic effect is associated with the restoration of gut microbiota, as demonstrated by fecal microbiota transplantation from C57BL/6 J controls and semaglutide-treated BTBR mice, which ameliorated the ASD behaviors in BTBR mice. Metabolomic profiling identified adrenic acid (AdA) as a crucial mediator; AdA levels in BTBR mice were lower but returned to normal following semaglutide treatment. Additionally, RNA sequencing revealed that hippocampal neurogenesis is associated with semaglutide treatment, and AdA supplementation restored social behaviors and hippocampal neurogenesis. These results highlight the critical role of the gut microbiota-brain axis in the therapeutic effects of semaglutide on ASD and suggest that targeting this axis alongside AdA may represent a promising strategy for ASD.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Semaglutide reduces autism-like behaviors in BTBR mice by changing gut bacteria

Abstract

Full Text

Funding

Competing interests

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