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Probiotics and prebiotics alleviate behavioral deficits, inflammatory response, and gut dysbiosis in prenatal VPA-induced rodent model of autism.

Physiology & behavior2022

Adıgüzel Emre, Çiçek Betül, Ünal Gökhan, Aydın Mehmet Fatih, Barlak-Keti Didem

What this study means for families

Researchers gave probiotics and prebiotics to rats with autism-like behaviors to see if these supplements could help. The treatments improved social skills, reduced anxiety, and decreased repetitive behaviors. They also helped balance gut bacteria and reduced inflammation. However, some autism-like symptoms didn't improve. While this is promising, these are animal studies, so we don't know yet if the same benefits would occur in autistic children.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Research summary

This animal study investigated whether probiotics and prebiotics could improve autism-like behaviors in rats exposed to valproic acid before birth. Researchers treated pregnant rats with VPA to create autism-like symptoms in offspring, then administered various combinations of probiotics and prebiotics. Results showed that probiotic and combined treatments significantly improved social behaviors and reduced anxiety. All treatments reduced repetitive behaviors.

However, treatments did not improve sensorimotor issues or despair-like behaviors. Probiotic treatment normalized inflammatory markers (IL-6 and IL-10) and improved the gut bacteria ratio. Combined treatment also restored serotonin levels in the brain's prefrontal cortex, suggesting gut-brain communication pathways may be therapeutic targets.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Key findings

  • 1

    Probiotic and combined treatments significantly improved sociability, social interaction, and anxiety parameters

    Confidence: moderateRelevance: Direct relevance to core autism symptoms of social communication difficulties
  • 2

    All treatments (probiotic, prebiotic, combined) reduced stereotypical behaviors

    Confidence: moderateRelevance: Addresses repetitive behaviors, a core autism diagnostic criterion
  • 3

    Probiotic treatment normalized inflammatory markers IL-6 and IL-10

    Confidence: moderateRelevance: Suggests anti-inflammatory mechanism potentially relevant to autism
  • 4

    Combined treatment restored serotonin levels in prefrontal cortex

    Confidence: moderateRelevance: Serotonin dysfunction is implicated in autism symptoms

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Clinical implications

Results suggest gut microbiome modulation may improve some autism symptoms through gut-brain pathways. However, treatments didn't address all autism-like behaviors. Human trials needed before clinical recommendations. May inform future research into microbiome-based interventions for autism spectrum conditions.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Limitations

Animal model using chemical induction may not fully represent human autism complexity. Sample sizes not reported. Single study without replication. Prenatal VPA model represents only one potential autism pathway. Unclear treatment duration and long-term effects not assessed.

Summary by AutismInsights from published abstract. This is not a substitute for reading the original paper.

Original abstract

Autism spectrum disorders are neuropsychiatric conditions characterized by social interaction and communication disorders and repetitive stereotypical behaviors. These disorders are also accompanied by an inflammatory status. Bidirectional communication between microbiome, gut, and brain has been discovered as a major mechanism influencing core symptoms and biomarkers of autism. Therefore, the modulation of the gut microbiota in autism has recently attracted interest.

In this study, probiotic- and prebiotic-mediated modulation of the gut microbiota was compared in terms of different symptoms and findings in an experimental autism model. Valproic acid (VPA) (500 mg/kg) was administered to Wistar rats (on prenatal day 12.5) to induce autistic-like behaviors. Based on the supply of probiotics and prebiotics, animals were grouped as control (saline), autistic-like (prenatal VPA), probiotic (prenatal VPA + 22.5 × 10cfu/day probiotic), prebiotic (prenatal VPA + 100 mg/day prebiotic), and combined treatment (prenatal VPA + 22.5 × 10cfu/day probiotic + 100 mg/day prebiotic). After the treatment process, behavioral tests (social behaviors, anxiety, stereotypical behavior, sensorimotor gating, and behavioral despair) and biochemical analyses (serum and brain tissue) were conducted, and the quantities of some phyla and genera were determined in stool samples.

Significant positive effects of probiotic and combined treatments were observed on the sociability, social interaction, and anxiety parameters. In addition, all three treatments had positive effects on stereotypical behavior. However, the treatments did not affect sensorimotor gating deficits and behavioral despair. Further, probiotic treatment reversed the VPA-induced increase and decrease in serum IL-6 and IL-10 levels, respectively.

Combined treatment also significantly increased the IL-10 levels. Prenatal VPA exposure decreased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex of the brain; however, combined treatment reversed this decrease. Prenatal VPA exposure also caused a decrease in Bacteroidetes/Firmicutes ratio in the gut microbiota, while the probiotic treatment significantly increased this ratio. These findings indicate that probiotic- and prebiotic-mediated microbial modulation may represent a new therapeutic approach to alleviate autistic-like symptoms.

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Evidence Grade

Emerging

limited

Grade assigned by AutismInsights based on study type and published abstract.

Study Details

Journal
Physiology & behavior
Year
2022
PMID
36100109
DOI
10.1016/j.physbeh.2022.113961

MeSH Terms

AnimalsAutism Spectrum DisorderAutistic DisorderDisease Models, AnimalDysbiosisFemaleHumansInterleukin-10Interleukin-6PrebioticsPregnancyPrenatal Exposure Delayed EffectsProbioticsRatsRats, WistarRodentiaSerotoninValproic Acid