Parabacteroides distasonis ameliorates methylphenidate hydrochloride-induced colonic inflammatory responses and associated gastrointestinal distress

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, with methylphenidate hydrochloride (MPH) as its first-line pharmacotherapy. Though effective, MPH is associated with underrecognized gastrointestinal adverse events warranting further investigation. Recently, the gut microbiota has attracted attention for treating gastrointestinal distress, but research on its role in alleviating MPH-induced gastrointestinal reactions remains scarce. Herein, Wistar-Kyoto rats (WKY) served as controls alongside spontaneously hypertensive rats (SHR) to explore MPH-induced gastrointestinal adverse drug reactions. The gastrointestinal phenotypes, colonic histopathological characteristics, and inflammatory factor levels were evaluated, and the gut microbiota profiles were analyzed via 16S rRNA gene sequencing. The protective effect of Parabacteroides distasonis ( P. distasonis ) was further verified by supplementing the treated rats with this strain. We demonstrated MPH induced diarrhea and colonic inflammatory responses in rats. 16S rRNA gene amplicon sequencing revealed that MPH-treated rats had significantly decreased gut microbiota health index, increased dysbiosis index, and reduced P. distasonis abundance, suggesting MPH-induced gastrointestinal reactions may correlate closely with reduced P. distasonis . Further experiments confirmed that P. distasonis supplementation effectively alleviated diarrhea and colonic inflammatory responses in MPH-treated rats. Collectively, this is the first study verifying that P. distasonis supplementation mitigates MPH-induced gastrointestinal adverse reactions, providing a novel intervention strategy to improve tolerance of ADHD pharmacotherapy.