Related Experiment Videos
Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
Shannon Rose1, Sirish C Bennuri1, Katherine F Murray2
1Autism Research Program, Arkansas Children's Research Institute, Little Rock, Arkansas, United States of America.
Abstract:
Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD) but the pathophysiology is poorly understood. Imbalances in the enteric microbiome have been associated with ASD and can cause GI dysfunction potentially through disruption of mitochondrial function as microbiome metabolites modulate mitochondrial function and mitochondrial dysfunction is highly associated with GI symptoms. In this study, we compared mitochondrial function in rectal and cecum biopsies under the assumption that certain microbiome metabolites, such as butyrate and propionic acid, are more abundant in the cecum as compared to the rectum. Rectal and cecum mucosal biopsies were collected during elective diagnostic colonoscopy. Using a single-blind case-control design, complex I and IV and citrate synthase activities and complex I-V protein quantity from 10 children with ASD, 10 children with Crohn's disease and 10 neurotypical children with nonspecific GI complaints were measured. The protein for all complexes, except complex II, in the cecum as compared to the rectum was significantly higher in ASD samples as compared to other groups. For both rectal and cecum biopsies, ASD samples demonstrated higher complex I activity, but not complex IV or citrate synthase activity, compared to other groups. Mitochondrial function in the gut mucosa from children with ASD was found to be significantly different than other groups who manifested similar GI symptomatology suggesting a unique pathophysiology for GI symptoms in children with ASD. Abnormalities localized to the cecum suggest a role for imbalances in the microbiome, potentially in the production of butyrate, in children with ASD.
Insights
Children with autism spectrum disorder (ASD) show distinct gut mitochondrial dysfunction, particularly in the cecum, suggesting microbiome imbalances may contribute to gastrointestinal issues in ASD.
Area of Science:
- Gastroenterology
- Neuroscience
- Metabolomics
Background:
- Gastrointestinal (GI) symptoms are common in autism spectrum disorder (ASD), but their underlying causes are not fully understood.
- The enteric microbiome and mitochondrial function are implicated in GI dysfunction, with microbiome metabolites potentially affecting mitochondrial activity.
Purpose of the Study:
- To investigate mitochondrial function in rectal and cecum biopsies from children with ASD compared to controls.
- To explore the potential role of microbiome metabolites, like butyrate, in the pathophysiology of GI symptoms in ASD.
Main Methods:
- A single-blind, case-control study involving 10 children with ASD, 10 with Crohn's disease, and 10 neurotypical children with GI complaints.
- Mitochondrial complex I, IV, and citrate synthase activities, along with complex I-V protein levels, were measured in rectal and cecum mucosal biopsies.
Main Results:
- ASD samples showed significantly higher protein levels for most mitochondrial complexes in the cecum compared to the rectum and controls.
- Children with ASD exhibited elevated complex I activity in both rectal and cecum biopsies, unlike other groups.
- Mitochondrial function in the gut mucosa of children with ASD differed significantly from controls with similar GI symptoms.
Conclusions:
- Mitochondrial dysfunction in the gut mucosa is a distinct feature in children with ASD, suggesting a unique pathophysiology for their GI symptoms.
- Abnormalities concentrated in the cecum point towards a potential role for microbiome imbalances, possibly involving butyrate production, in ASD-associated GI issues.