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

Abstract

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.

Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease

“…BDNF is of particular importance in HD as a variety of studies have reported reduced levels in both patients and animal models ( 46 – 48 ), which is likely to have implications for neuronal survival. Prior studies have found evidence of a KD-driven increase in BDNF levels ( 49 , 50 ) although these findings were not universal ( 51 ). A larger number of transcripts were altered by both genotype and diet and more importantly, several exhibited a significant interaction between these two factors including, among others Adora2a, Nos1 , Homer1 , and Il6ra ( Figure 3 , Supplementary Figure 1 , and Table 2 ).…”

“…Prior studies have found evidence of a KD-driven increase in BDNF levels (49,50) although these findings were not universal (51). A larger number of transcripts were altered by both genotype and diet and more importantly, several exhibited a significant interaction between these two factors including, among others Adora2a, Nos1, Homer1, and Il6ra (Figure 3, Supplementary Figure 1, and Table 2).…”

Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut–Brain Axis

“…Additionally, a ketogenic diet has been shown to produce a dual effect in improving the 5-HT and BDNF systems. The rats exhibited an upregulation of the BDNF receptor TrkB as a counteracting response to a stress-induced reduction in neurotrophin levels [ 60 ].…”

The Relationship between Diet, Gut Mycobiome, and Functional Gastrointestinal Disorders: Evidence, Doubts, and Prospects

“…Previous studies indicated KD might be helpful in improving IBS symptoms by repairing the gut‐brain axis and reducing harmful effects of stress on gut mitochondrial biogenesis. [ 79,80 ] KD and Atkins diet showed notable ability in anti‐inflammation, reducing oxidative stress. The low proportions of carbohydrates in these diets may help reduce fungal infections including C. albicans .…”