Fructose malabsorption triggers CCK release through fructose metabolism by gut microbiota

What is it about?

Fructose consumption rose in the recent human history to the point that > 50% of the population cannot fully absorb the average daily intake amount. Moreover, children, the age group consuming highest amount of fructose, are the most susceptible to fructose malabsorption. Fructose malabsorption is commonly associated with bloating, diarrhea, visceral hypersensitivity and depression. However, the fundamental mechanisms by which fructose leads to those pathologies remain unknown. Although many studies have demonstrated the role of gut bacteria in the health of the host, the interactions between fructose and intestinal bacteria are poorly studied. Here we tested the hypothesis that malabsorption of dietary fructose modifies the composition of bacteria in the lower intestine and thereby influences the endocrine functions of the intestine. We used a mouse model with a mutation in the ketohexokinase (KHK) gene which prevents efficient absorption of fructose. We demonstrated that when fructose reaches the lower regions of the gastrointestinal tract it modifies the composition and functions of the microbiota. This dysbiotic microbiota was able to regulate the pattern of peptides produced by the L-cells in the caecum, especially stimulating the production of CCK which is normally secreted only by the endocrine cells located in the upper region of the gut. Since the CCK in known to mediate the visceral pain in other gastrointestinal pathologies our results provide a possible explanation for the pain experienced by fructose mal-absorbing patients, and identify a number of potential therapeutic entry points to alleviate this condition.

Featured Image

Why is it important?

Fructose malabsorption is largely underestimated in human population and is associated with major gastrointestinal symptoms. No treatment is currently available other than a major reduction in fructose intake which can be challenging since fructose is present in numerous fruits. The findings of our paper may open the route for new therapeutics perceptive for patients.