Excess dietary sugar impairs colonic epithelial regeneration 1 in response to damage

Burr et al. (BiorXiv) doi: 10.1101/2021.08.18.456840

Keywords

  • Diet

  • Intestinal epithelial cells

  • Intestinal injury

 

Main Findings

Our diet composition has drastically changed in the last 40 years. The rate of sugar consumption, particularly simple carbohydrates sugar that are absorbed by the host without further processing, has increased by 127%. Interestingly, the incidence of chronic inflammatory disease such as IBD also increased and follow a similar trend associated with  the “westernization” of the diet. Despite this epidemiologic correlation, little is known about the link between excessive sugar diet and the prevalence of IBD nor the consequence of excessive sugar consumption on the severity of IBD symptoms. Several studies have suggested that diet primarily impact on the gut microbiome composition which could subsequently favour IBD onset. Here the authors explore the impact of a high sugar diet on intestinal barrier regeneration in vivo using the Dextran Sodium Sulfate (DSS) colitis mice model to induce colonic epithelial injury. They find that high sugar diet given for two weeks before DSA impacts the severity of DSS colitis and accelerate epithelial cell damage. Interestingly, the effect of high sugar diet had no impact on the microbiome composition before DSS colitis induction and faecal transplantation of microbiome from high sugar diet mice into germfree mice did not recapitulate the phenotype observed in wild type animal suggesting that sugar exerts is activity directly onto the host. Then, they show that colonic epithelial cell absorbs and accumulates the excess of sugar from the diet which impairs their ability to proliferate. Metabolically, the sugar absorbed by colonic epithelial cell activates glycolysis but is not transferred into the Kreb’s cycle to boost aerobic respiration. Biochemically boosting pyruvate flux through the Kreb’s cycle by inhibiting pyruvate dehydrogenase kinase rescued sugar-impaired colonoid development. They conclude that excess dietary sugar can directly inhibit epithelial proliferation in response to damage and may inform diets that better support the treatment of acute intestinal injury

 

Limitations

 

Excess dietary sugar effect on immune cells function was not analysed.

The consequences of sugar excess on the microbiome or the host immune response in a long term setting were not explored

The mechanisms by which excess of glycolysis metabolites impairs epithelial cell proliferation without inducing cell death remains unknown.

 

Significance/Novelty

 

Despite several decades of research on the pathophysiology of IBD and its aetiology, the effect of environmental factors and in particular our diet remains unexplored. Studies trying to explore the impact of environmental factors on IBD severity are mostly epidemiologic and lack function. This study is a rare example of an attempt to functionally understand the consequence of a diet component on the host immune response. This study emphasised the consequence of diet in the management of IBD and suggest that patients treated for inflammatory bowel diseases presenting with epithelial damage such as ulcers might benefits from controlling sugar input in their diet in parallel to medication. This study may create curiosities amongst researcher to understand better the impact of our diet composition on IBD severity and its therapeutic management.

 

Credit

Reviewed by Mathilde Pohin as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford.