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Early-Life Ceftriaxone-Induced Gut Microbiota Perturbation Persistently Exacerbates Juvenile ADHD-Like Behaviours via
Yang Yang1, Simou Wu1, Jianxiu Liu1
1Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, P.R. China.
Insights
Early life antibiotic exposure disrupted gut microbiota in rats, leading to persistent ADHD symptoms and neuroinflammation. Specific gut bacteria like Lactobacillus and Clostridia were linked to ADHD development.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Gut microbiota dysbiosis in early life is increasingly linked to neurodevelopmental disorders.
- Antibiotic use can significantly alter the gut microbiome composition and function.
- The microbiota-gut-brain axis plays a crucial role in regulating behavior and immune responses.
Purpose of the Study:
- To investigate the long-term effects of ceftriaxone-induced gut microbiota perturbation on juvenile ADHD symptoms in rats.
- To examine alterations in immune pathways within the microbiota-gut-brain axis following antibiotic exposure.
- To identify specific gut microbial taxa associated with ADHD development and severity.
Main Methods:
- Neonatal male spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were treated with ceftriaxone during lactation.
- ADHD-related behaviors were assessed using the 5-choice serial reaction time task (5-CSRTT) and open-field test (OFT).
- Gut microbiota composition, immune cell populations (Treg), and cytokine expression (IL-10, IL-6) were analyzed.
Main Results:
- Ceftriaxone treatment caused persistent gut microbiota disruption in both rat strains.
- Juvenile WKY rats showed inattention and impulsivity, while SHR rats exhibited severe hyperactivity and neuroinflammation.
- Decreased microbial diversity (Chao1, Shannon) correlated with increased Treg cells and IL-10, but negatively with ADHD symptoms.
- Specific bacteria (Lactobacillus, Clostridia_UCG-014) were negatively associated with ADHD, while Muribaculaceae showed a protective association.
Conclusions:
- Early-life gut microbiota perturbation contributes to the onset and exacerbation of juvenile ADHD.
- Neuroinflammation and peripheral immune dysfunction are key mechanisms linking gut dysbiosis to ADHD.
- Specific gut microbial compositions may influence ADHD development and present potential therapeutic targets.
Abstract:
This study investigated the impact of ceftriaxone-induced gut microbiota perturbation in neonatal male spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats during lactation on the development of juvenile ADHD symptoms. The 5-choice serial reaction time task (5-CSRTT) and open-field test (OFT) were used to evaluate ADHD-related behaviours, and alterations in immune pathways within the microbiota-gut-brain axis were examined. At 3 weeks old, the gut microbiota in both WKY and SHR was significantly disrupted following antibiotic intervention, with these changes persisting 4 weeks after ceftriaxone withdrawal. At the juvenile stage, WKY exhibited inattention, impulsivity, and hyperactivity, while SHR had severe hyperactivity and neuroinflammation. Decreased Chao1 and Shannon indices were positively associated with Treg cells in the spleen, mesenteric lymph nodes (MLN), and IL-10 mRNA expression in the striatum; further, the latter biochemical indices were negatively associated with ADHD symptoms. Lactobacillus and Clostridia_UCG-014 negatively correlated with Treg cells in the spleen, MLN, IL-6, and IL-10 mRNA expression in the striatum; further, these biomarkers were negatively associated with ADHD, which suggested they may contribute to the development of ADHD. In contrast, Muribaculaceae positively correlated with Treg cells in the spleen and MLN, IL-10 mRNA expression, and negatively correlated with ADHD symptoms. These results suggest that early life gut microbiota perturbation persistently contributes to the onset and aggravation of juvenile ADHD through the exacerbation of neuroinflammation and peripheral immune dysfunction.
