Early‐Life Ceftriaxone‐Induced Gut Microbiota Perturbation Persistently Exacerbates Juvenile ADHD‐Like Behaviours via Immune Dysfunction in SHR/WKY Rats

TL;DR

Early-life antibiotic use disrupts gut bacteria in rats, leading to long-term ADHD-like behaviors and immune issues.

Contribution

Shows how early gut microbiota disruption causes persistent ADHD-like behaviors via immune dysfunction in rats.

Findings

Gut microbiota disruption from ceftriaxone in neonatal rats persisted weeks after treatment.

SHR rats showed severe hyperactivity and neuroinflammation, while WKY rats showed inattention and impulsivity.

Certain gut bacteria correlated with immune markers and ADHD symptoms, suggesting a causal role in behavior.

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.

After early life gut dysbiosis by antibiotic, SHR had a sever hyperactivity and neuroinflammation, and WKY became inattentive, impulsive and more hyperactive in juvenile.

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