Fecal Microbiota Transplantation for Attention-Deficit/Hyperactivity Disorder: Mechanisms, Evidence, and Future Directions.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. While pharmacological and behavioral therapies remain first-line treatments, their limitations in efficacy, tolerability, and long-term adherence underscore the need for innovative interventions. Growing evidence highlights the role of the microbiota-gut-brain axis (MGBA) in ADHD pathophysiology, particularly involving immune dysregulation, neurotransmitter imbalance, metabolic disruption, and epigenetic alterations. Fecal microbiota transplantation (FMT), as a microbiota-based intervention, has shown promise in restoring MGBA homeostasis and modulating neural function through multiple mechanisms. This review summarizes current preclinical and clinical research on FMT in ADHD, covering its effects on neuroinflammation, neurotransmitter pathways, vagus nerve and HPA axis signaling, and epigenetic reprogramming. Although preclinical models and early human data indicate potential behavioral benefits and mechanistic plausibility, methodological heterogeneity, limited sample sizes, and incomplete mechanistic validation pose significant challenges. Future research should prioritize protocol standardization, randomized controlled trials, biomarker discovery, and ethical regulation to facilitate the safe and effective clinical translation of FMT in ADHD treatment.