Cannabinoid Receptors Overexpression in a Rat Model of Irritable Bowel Syndrome (IBS) after Treatment with a Ketogenic Diet

Gigante, Isabella; Tutino, Valeria; Russo, Francesco; Nunzio, Valentina De; Coletta, Sergio; Armentano, Ricardo L.; Crovace, Alberto Maria; Caruso, Maria Gabriella; Orlando, Antonella; Notarnicola, Maria

doi:10.3390/ijms22062880

Cited by 10 publications

(13 citation statements)

References 49 publications

(31 reference statements)

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“…As recently published elsewhere by our group, we have already demonstrated the effectiveness of KD in ameliorating intestinal membrane functions and gut mitochondrial biogenesis in the animal model of IBS, along with the inflammatory status [35,36].…”

Section: Discussionsupporting

confidence: 62%

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

Orlando

Chimienti

Notarnicola

et al. 2022

IJMS

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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.

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Section: Discussionsupporting

confidence: 62%

“…Additionally, it is now accepted how altered communication between the gut and the brain can contribute to intestinal and psychological dysfunctions observed in IBS [4]. In this framework, and derived mainly from preliminary results in animal studies [34][35][36], KD could show some interesting therapeutic potentiality.…”

Section: Discussionmentioning

confidence: 99%

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

Orlando

Chimienti

Notarnicola

et al. 2022

IJMS

Self Cite

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“…The pharmacological inhibition of FAAH has been shown to reduce inflammation and to promote gut healing ( Sasson et al, 2006 ). Cannabinoid receptors also mediate the low-carbohydrate diet-induced improvement in the gastro-intestinal function and provide protection to the intestinal crypt base ( Gigante et al, 2021 ). In the mouse model of chemical-induced colitis, CB1R protects from the pro-inflammatory responses, while the genetic deficiency of CB1R induces stronger inflammatory responses ( Massa et al, 2004 ).…”

Section: The Intestinal Endocannabinoid Systemmentioning

confidence: 99%

The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism

Srivastava

Lutz

Azúa

2022

Front. Cell. Neurosci.

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The endocannabinoid system, with its receptors and ligands, is present in the gut epithelium and enteroendocrine cells, and is able to modulate brain functions, both indirectly through circulating gut-derived factors and directly through the vagus nerve, finally acting on the brain’s mechanisms regarding metabolism and behavior. The gut endocannabinoid system also regulates gut motility, permeability, and inflammatory responses. Furthermore, microbiota composition has been shown to influence the activity of the endocannabinoid system. This review examines the interaction between microbiota, intestinal endocannabinoid system, metabolism, and stress responses. We hypothesize that the crosstalk between microbiota and intestinal endocannabinoid system has a prominent role in stress-induced changes in the gut-brain axis affecting metabolic and mental health. Inter-individual differences are commonly observed in stress responses, but mechanisms underlying resilience and vulnerability to stress are far from understood. Both gut microbiota and the endocannabinoid system have been implicated in stress resilience. We also discuss interventions targeting the microbiota and the endocannabinoid system to mitigate metabolic and stress-related disorders.

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“…Several clinical studies have shown that KD a reduction of midlife mortality and a prolongation of health due to its ability to control body weight and its beneficial effects in the prevention of type 2 diabetes, cancer, and neurological diseases [3][4][5][6]. Recently, in a rat model of irritable bowel syndrome (IBS), KD was able to restore intestinal cell damage through the upregulation of endocannabinoids receptors (CB1-R and CB2-R) [7] improving intestinal permeability. Besides, the KD administration positively compensatory mechanisms able to reduce inflammation and oxidative stress in the gut, restoring mitochondrial function and baseline autophagy [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, in a rat model of irritable bowel syndrome (IBS), KD was able to restore intestinal cell damage through the upregulation of endocannabinoids receptors (CB1-R and CB2-R) [7] improving intestinal permeability. Besides, the KD administration positively compensatory mechanisms able to reduce inflammation and oxidative stress in the gut, restoring mitochondrial function and baseline autophagy [7,8].…”

Section: Introductionmentioning

confidence: 99%

Liver Fatty Acids Profile of Rats Fed Ketogenic Diet

Notarnicola

2022

BJSTR

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The administration of a low-carbohydrate, and high-fat ketogenic diet (KD) has been demonstrated to exert beneficial effects on gastrointestinal mucosa in rats. Therefore, the present study was aimed to investigate whether the KD treatment, able to reduce the inflammation at the intestinal level, could also affect rat liver function. After weaning at 5 weeks of age, 12 Wistar rats were fed standard diet (control group), and 13 animals were fed KD. After ten weeks of treatment, animals were sacrificed and the liver from each animal was collected and stored at -80°C until assayed. Fatty acids extracted from liver tissue were quantified by a gas chromatographic method. Western blotting analysis and ELISA method were used to evaluate the inflammation and antioxidant biomarkers in rat liver, respectively. The levels of single saturated fatty acids and monounsaturated fatty acids were significantly decreased in hepatic tissue after KD treatment. A significant decrease was also observed for the content of arachidonic acid, an omega-6 polyunsaturated fatty acid. All main omega-3 polyunsaturated fatty acids, except for eicosapentaenoic acid, were significantly increased in liver tissue from rat treated with KD. Compared to the control group, a significant increase of the SOD 1 and SOD 2 protein enzymes, was found in the liver of KD-treated rats. KD treatment on the one hand promotes the increase of tissue inflammation status in the rat liver, on the other it was able to activate defense mechanisms to protect liver environment.

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Cannabinoid Receptors Overexpression in a Rat Model of Irritable Bowel Syndrome (IBS) after Treatment with a Ketogenic Diet

Cited by 10 publications

References 49 publications

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

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

The Microbiome and Gut Endocannabinoid System in the Regulation of Stress Responses and Metabolism

Liver Fatty Acids Profile of Rats Fed Ketogenic Diet

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