The Ketogenic Diet Improves Gut-Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems

Int J Mol Sci. 2022 Jan 20;23(3):1098. doi: 10.3390/ijms23031098.


Altered gut-brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.

Keywords: 5-HT; BDNF; animal model; irritable bowel syndrome; ketogenic diet.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Brain-Gut Axis / drug effects*
  • Diet, Ketogenic / methods*
  • Disease Models, Animal
  • Irritable Bowel Syndrome / diet therapy*
  • Irritable Bowel Syndrome / etiology
  • Irritable Bowel Syndrome / metabolism
  • Irritable Bowel Syndrome / pathology
  • Male
  • Maternal Deprivation*
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism*
  • Serotonin / blood
  • Stress, Psychological / complications*


  • Brain-Derived Neurotrophic Factor
  • Receptors, Serotonin
  • Serotonin