Effect of metformin in autistic BTBR T + Itpr3tf/J mice administered a high-fat diet.

Scientists studied mice with autism-like traits to see how a high-fat diet affects their behavior and whether the diabetes medication metformin could help. Surprisingly, the high-fat diet actually improved the mice's social behavior but made repetitive behaviors worse. The diet changed their gut bacteria and brain chemicals. Metformin reduced hyperactivity and brain inflammation but didn't significantly improve autism-related behaviors overall.

This study investigated how high-fat diet affects autism-related behaviors in BTBR mice, an animal model for autism spectrum disorder, and whether metformin could provide therapeutic benefits. Researchers examined the interplay between diet, gut microbiota, serotonin levels, and autistic behaviors. Unexpectedly, high-fat diet improved social behavior in BTBR mice while worsening repetitive behaviors. The diet altered gut microbiota composition, increased the Firmicutes/Bacteroidetes ratio, and modified serotonin levels (decreased in gut, increased in brain cortex).

Metformin reduced diet-induced hyperactivity and hippocampal inflammation but showed no significant positive effects on core autism-related behaviors. Specific gut bacteria correlated with behavioral scores and serotonin levels, suggesting microbiota-gut-brain axis involvement in autism-related phenotypes.

Findings suggest complex relationships between diet, gut microbiota, and autism behaviors that warrant careful clinical investigation. The unexpected social improvements with high-fat diet challenge simplistic diet recommendations and highlight need for personalized approaches in autism management.

Animal model findings may not translate to humans. Sample size not reported. Study design unclear. Limited assessment of autism-related behaviors. Short-term intervention period may not capture long-term effects.

The biological mechanisms linking diet-related obesity and autism-related behaviors remain unclear. We aimed to characterize these interactions, focusing on gut microbiota, 5-hydroxytryptamine (5-HT) levels, and autistic behaviors in an animal model for autism; a high-fat diet (HFD) BTBR T + Itpr3tf/J (BTBR) mouse. In this model, we also examined the medication effects of metformin (Met) which is known to ameliorate several symptoms of autism spectrum disorder (ASD). Therefore, we hypothesized that HFD exacerbates BTBR autistic symptoms, which can be alleviated by Met, and the effects are associated with serotonin and the microbiota.

As expected, compared with mice fed a normal diet, ten-week HFD-fed mice showed increased body weight, adiposity, and glucose levels. HFD consumption markedly aggravated repetitive behaviors in the self-grooming test. Met reduced HFD-induced hyperactivity. Notably, HFD intervention rescued sociability in the three-chamber sociability test.

Furthermore, HFD stimulated tryptophan production, which was inhibited by Met. In contrast, 5-HT levels were lower in the gut and higher in the cortex in the HFD group. Moreover, Met suppressed inflammation in the hippocampus of HFD-fed mice by significantly downregulating the expression of pro-inflammatory cytokines (NF-κB, IL-17A, and IL-6). HFD increased the Firmicutes/Bacteroidetes ratio, and Met supplementation decreased richness while increasing bacterial diversity.

We found that the abundance of gut microbiota (Lachnoclostridium, Anaerotruncus, Mucispirillum, and Lactococcus) was correlated with behavior scores and 5-HT levels. Overall, HFD consumption improved sociality in BTBR mice, which was related to the modulation of 5-HT levels and the composition of the microbiota. Met did not show any significant positive effects on the autism phenotype associated with HFD.