Mitochondrial Dysfunction and Reduced TCA Cycle Metabolite Levels in Inflammatory Bowel Disease Patients.

INTRODUCTION

Inflammatory bowel disease (IBD) mainly includes ulcerative colitis (UC) and Crohn's disease (CD). These diseases are classified as chronic and recurrent inflammatory diseases affecting the digestive tract. An energy deficiency in intestinal cells is believed to be associated with IBD pathology.

METHODS

Our study investigated the bioenergetic functionality of mitochondria using the plasma of patients with CD and UC by determining the concentration of intermediates of the tricarboxylic acid cycle (TCA), such as acetyl coenzyme A, succinate, fumarate, α-ketoglutarate, NADH2, IDH2, Cytochrome C Oxidase, Cytochrome C Reductase, and ATP.

RESULTS

Our results show an imbalance in mitochondrial homeostasis and bioenergetics, demonstrated by reduced activity of respiratory complexes and reduced production of TCA intermediates in the plasma of patients with CD and UC. In the group of patients with CD, treatment with corticosteroids had a significant positive effect, as significantly higher IDH2 and succinate levels were found. Correlation analyses of mitochondrial functionality biomarkers with other blood markers revealed a significant relationship between CRP and ATP levels, with higher CRP significantly linked to lower ATP and a similar trend for succinate levels. Using the disease activity scale, we show that biomarkers such as IDH2, α-ketoglutarate, and succinate levels are significantly lower in patients with higher disease activity.

CONCLUSION

We conclude that reduced metabolites and respiratory complexes associated with the TCA indicate mitochondrial bioenergetic failure in IBD patients. Besides, Krebs cycle metabolites can be a good marker of predisposition to the disease and the course of IBD. They can be easily determined in a blood sample taken from the patient. Pharmacological protection of mitochondria in individuals predisposed to IBD development and compensation for the changed function of mitochondria in persons with the developed disease may become a new approach to personalized therapies focused on restoring the proper activity of mitochondrial enzymes.