Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway.

Researchers studied 'leaky gut' in mice with autism-like behaviors. When they made the gut barrier worse, social behaviors decreased. When they used metformin (a diabetes medication) to repair the gut barrier, the mice showed better social skills, less repetitive behaviors, and reduced anxiety. The treatment also lowered harmful bacterial toxins in the blood and reduced brain inflammation. This suggests that gut problems might contribute to autism symptoms through inflammation.

This pre-clinical study investigated the role of intestinal barrier dysfunction ('leaky gut') in autism using BTBR mice, an established autism model. Researchers used dextran sulfate sodium (DSS) to worsen gut barrier function and metformin to repair it. DSS treatment decreased social behaviors, while metformin improved social proximity, social memory, and reduced repetitive and anxiety-related behaviors. The study found that metformin reduced blood lipopolysaccharide levels and suppressed inflammatory signaling through the TLR4-MyD88-NF-κB pathway in the brain cortex.

The findings suggest that compromised gut barrier function may contribute to autism development through bacterial toxin-mediated neuroinflammation.

Suggests gut barrier integrity may influence autism symptoms through inflammatory pathways. Supports investigation of gut-targeted interventions. However, animal model findings require human validation before clinical application. May inform future research on microbiome and anti-inflammatory treatments.

Animal study using mice, limiting direct translation to humans. Sample size not reported. Study type unclear. Single study without replication. Metformin effects may not be specific to gut barrier repair.

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR Ttf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin.

We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.