High-Fat Diet Exacerbates Behavioral and Neurochemical Deficits in BTBR Mice: Linking Intestinal Inflammation and Brain Neurotransmitter Dysregulation to Melatonin Therapeutic Potential.

Scientists studied mice with autism-like traits and found that a high-fat diet made their social problems and anxiety worse. The diet also reduced important brain chemicals and caused gut inflammation. However, when the mice were given melatonin (a natural hormone), their behavior improved, brain chemistry normalized, and gut inflammation decreased. This suggests diet affects autism symptoms and melatonin might help.

This preclinical study examined how high-fat diet affects autism-like behaviors in BTBR mice, an established autism model, and tested melatonin as a potential intervention. Researchers found that high-fat diet worsened anxiety-like behaviors and social deficits in BTBR mice, alongside decreased brain neurotransmitters (serotonin and dopamine) and increased intestinal inflammation. Melatonin treatment effectively reversed these negative effects, improving autism-like behaviors, restoring brain neurotransmitter levels, and reducing gut inflammation. The study suggests a gut-brain connection in autism symptoms and supports melatonin's therapeutic potential through its effects on both neurochemical and gastrointestinal systems.

Results suggest dietary modifications and melatonin supplementation warrant investigation in autism. However, human studies are needed before clinical recommendations. The gut-brain connection findings support holistic approaches addressing both gastrointestinal and neurological aspects of autism.

Animal study using mouse model may not fully translate to humans. Small sample sizes not clearly specified. Short intervention periods (4-6 weeks) limit understanding of long-term effects. Mechanisms of gut-brain interaction require further investigation.

This study aims to investigate the effects of high-fat diet (HFD) on behavioral symptoms, brain neurotransmitters and intestinal inflammation in autism spectrum disorders (ASD) model mice-BTBR Ttf/J (BTBR) mice, and the effect of melatonin intervention. In a two-phase design, when investigating the effects of HFD, 16 C57 mice and 16 BTBR mice were divided into two groups and subjected to HFD or normal diet (ND) for 4 weeks; when investigating the effects of melatonin, 32 BTBR mice were divided into two groups and subjected to HFD or ND for 4 weeks, followed by melatonin or vehicle treatment for another 2 weeks. Behavioral assessments were performed at post-intervention phases, followed with determination of brain neurotransmitters-serotonin (5-hydroxy tryptamine, 5-HT) and dopamine (DA), and gastrointestinal inflammatory mediator analysis. Our findings demonstrate that HFD exacerbates anxiety-like behaviors and social deficits which may be mediated through brain neurotransmitter and gut, characterized by concomitant decrease of cerebral 5-HT and DA stores, coupled with intestinal inflammation.

Meanwhile, melatonin administration effectively ameliorated ASD-like behavior, increased 5-HT and DA expressive levels in brain tissues and attenuated intestinal inflammation in HFD BTBR mice.