Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder

Sep 15, 2026

Uploaded by Oliver

Prebiotic diet can influence the microbiota-gut-brain axis by shaping gut microbial balance and immune homeostasis. This study tested whether a diet containing 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1) mitigates adverse outcomes from in utero valproic acid exposure in mice. Results show normalization of VPA-induced immune and gut alterations, reduced cerebellar neuroinflammation, and improved social and cognitive behavior, with restoration of key microbial taxa and intestinal permeability.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Autism spectrum disorder and the gut-brain axis

Rationale for prebiotics

Methods

Animal model and dietary intervention

Results

Microbial taxa, intestinal permeability, and immune homeostasis

Neuroinflammation and behavioral outcomes

Conclusion

[www.nature.com/aps](www.nature.com/aps) Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder Naika Prince1, Lucia N Peralta Marzal 1, Anastasia Markidi1,2, Sabbir Ahmed1, Youri Adolfs3, R Jeroen Pasterkamp3, Himanshu Kumar4, Guus Roeselers4, Johan Garssen 1,4, Aletta D Kraneveld 1,5 and Paula Perez-Pardo 1 ✉ | | Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deﬁcits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deﬁcits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on speciﬁc diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing speciﬁc prebiotic ﬁbers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11) . Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet,(2) in utero PBSexposed with GOS/FOS diet,(3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinﬂammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD. | | | | --- | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | -brain axis | | | | | | | | | | | | | | | Acta Pharmacologica Sinica (2024) 45:1591–1603; [https://doi.org/10.1038/s41401-024-01268-x](https://doi.org/10.1038/s41401-024-01268-x) | | | | | | | | Keywords: autism spectrum disorder; prebiotics; gastrointestinal microbiome; immunomodulation; gut INTRODUCTION Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders marked by social interaction, communication difﬁculties and cognitive deﬁcits [1, 2], as well as repetitive or restricted behaviors. Over the past decade, the global prevalence of ASD has increased, and the disorder is four times more likely to occur in boys than in girls [3, 4] . The exact etiology of ASD is not fully understood; however, emerging research indicated asigniﬁcant interplay between genetic susceptibilities and environmental inﬂuences, including accumulating evidence suggesting the potential involvement of the gut-brain in its pathogenesis. A meta-analysis revealed that children with ASD experience four times more gastrointestinal (GI) problems than controls [5] . Another study reports a correlation between the GI problems and the severity of the behavioral problems [6] . Evidence supporting the involvement of the gut-brain axis includes studies analyzing the gut microbiota composition of individuals with ASD, which have reported alterations in the microbial population [7] . Animal studies support this association as well, with studies demonstrating that microbiota transplantation from individuals wi

FAQs

What condition and model does the study focus on?

The study focuses on autism spectrum disorder (ASD) using a mouse model. Pregnant mice were exposed to valproic acid in utero to induce ASD-related phenotypes.

What prebiotic diet intervention was tested?

A diet containing 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1) was used. Diet intervention started at birth and continued throughout the experiment.

How did the prebiotic diet affect immune and gut outcomes?

The prebiotic diet normalized valproic-acid-induced changes, including restoration of key microbial taxa, intestinal permeability, and peripheral immune homeostasis.

What behavioral and brain effects were observed?

Prebiotic treatment reduced neuroinflammation in the cerebellum and improved impairments in social behavior and cognition in the mice.

Sep 15, 2026

Uploaded by Oliver