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

PLoS One. 2023 Aug 16;18(8):e0289133. doi: 10.1371/journal.pone.0289133. eCollection 2023.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common mental behavioral disorder in children. Alterations in gut microbiota composition are associated with neurological disorders. We aimed to investigate whether a ketogenic diet (KD) can be an alternative therapy for ADHD by altering the gut microbiota. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomly allocated to the normal diet (ND), methylphenidate (MPH), and KD groups. SHR in groups KD and MPH exhibited a significant increase in behavioral characteristics of ADHD, such as distance moved and immobility time. KD and MPH treatment led to a significant elevation in concentrations of 5-HT, AC, cAMP, and NE of brain tissue and the expression of DRD1, DAT, PKA, DARPP32, and cAMP at the protein level in WKY rats and SHR. KD and MPH significantly increased the richness and diversity of gut microbiota in SHR. The abundance of Ruminococcus_gauvreauii_group, Bacteroides, Bifidobacterium, and Blautia significantly increased, whereas that of Lactobacillus, Romboutsia, Facklamia, and Turicibacter significantly declined in the KD group compared with the ND group. The gut microbiota in the 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 microbiota. This study provides novel insights for the use of KD in treating ADHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Central Nervous System Stimulants*
  • Diet, Ketogenic*
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Male
  • Methylphenidate* / therapeutic use
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY

Substances

  • Central Nervous System Stimulants
  • Methylphenidate

Grants and funding

This work was supported by Key Research and Development Project of Shaanxi Province of Science and Technology Department of Shaanxi Province [grant number S2022-YF-YBSF-0892]. YL received the award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.