Ketogenic diet ameliorates attention deficit hyperactivity disorder in rats via regulating gut microbiota

Attention deficit hyperactivity disorder (ADHD) is a common mental behavioral disorders in children. Alterations in gut microbiota composition are associated with neurological disorders. We aimed to investigate whether ketogenic diet (KD) has potential to be an alternative therapy for ADHD through gut microbiota. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomly allocated to normal diet (ND) group, methylphenidate (MPH) group, and KD group. KD and MPH significantly alleviated behavioral characteristics (moving distance and immobility time) of ADHD in SHR. KD and MPH treatment led to a significant elevation in concentrations of 5-HT, AC, cAMP, and NE of brain tissue and in protein expression of DRD1, DAT, PKA, DARPP32, and cAMP in WKY rats and SHR. KD and MPH significantly increased richness and diversity of gut microbiota in SHR. Abundance of Ruminococcus_gauvreauii_group, Bacteroides, Bifidobacterium, and Blautia significantly increased whereas Lactobacillus, Romboutsia, Facklamia, and Turicibacter significantly declined in KD group compare to ND group. Gut microbiota in KD group of SHR mainly participated in amino acid metabolism- and sugar metabolism-related pathways. KD might alleviate behavioral disorders in ADHD by regulating gut microbiot. This study provides novel ideas for development of KD in ADHD treatment