High-Sugar Diet Damaging the Gut May Worsen Inflammatory Bowel Disease (IBD)

Diet containing increased amounts of sugar may interrupt the function of resident intestinal stem cells (ISCs) that maintain gut lining after inflammatory damage.

Cells that renew the colon’s lining could be affected by excess sugar present in the diet in a mouse model of inflammatory bowel disease (IBD), according to a new study by University of Pittsburgh scientists.

The prevalence of IBD is rising around the world, and it is rising the fastest in cultures with industrialized, urban lifestyles, which typically have diets high in sugar (). Too much sugar is not good for a variety of reasons, and the new study published in Cellular and Molecular Gastroenterology and Hepatologyadds to that evidence by showing how sugar may be harmful to the gut.

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‘Consuming excess dietary sugars can directly modulate intestinal cells’ regenerative proliferation, aggravating the symptoms of Inflammatory Bowel Disease (IBD).’

In this study, researchers started by feeding mice either a standard or high-sugar diet. Then they mimicked symptoms of IBD by treating the animals with a chemical called DSS that causes damage to the colon.

To their shock, all the mice on the high-sugar diet died within nine days. In contrast, all the animals on the standard diet survived until the end of the 14-day experiment. To learn what made sugar so deadly in mice with IBD symptoms, the team looked at the animals’ colons. Also known as the large intestine.

The colon is lined with a layer of epithelial cells that are arranged in finger-like projections called crypts. In a healthy colon, these cells are continually replenished by dividing stem cells at the bottom of each crypt. It takes five days for cells to travel through the circuit from the bottom to the top of the crypt, where they are shed into the colon and defecated out. You essentially make a whole new colon every five days.

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When mice on the high-sugar diet were given DSS, that circuit collapsed. In some of the animals, the protective layer of epithelial cells was completely lost, causing the colon to be full of blood and immune cells.

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Unexpectedly, a high-sugar diet was similarly lethal in germ-free mice treated with DSS, showing that sugar affects the colon directly and is not dependent on the gut microbiome as the researchers had predicted.

Next, they tested how sugar affected mouse and human colonoids, poppy seed-sized miniature intestines that can be grown in a lab dish. As concentrations of glucose, sucrose, or fructose increased, fewer colonoids developed and they grew slower, evidence that sugar impaired cell division ().

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They found that stem cells were dividing much more slowly in the presence of sugar — likely too slow to repair damage to the colon. The other strange thing was that the metabolism of the cells was different. These cells usually prefer to use fatty acids, but after being grown in high-sugar conditions, they seemed to get locked into using sugar.

Researchers suspect that this rewiring of cellular pathways inhibits the capacity of stem cells to divide, slowing the renewal of the colon lining and accelerating gut damage in IBD. These findings could help explain other research that has linked sweetened beverages, including sodas, soft drinks, and juices, to negative outcomes in IBD patients ().

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They also suggest that consuming high levels of sugar could have negative outcomes for repairing the colon in patients with inflammatory bowel disease. In future research, researchers will focus on understanding how diet and immune response can affect IBD.

References:

Dietary Intake of Total Carbohydrates, Sugar and Sugar-Sweetened Beverages, and Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies - (https://www.frontiersin.org/articles/10.3389/fnut.2021.707795/full )
Sugar-sweetened beverages exacerbate high-fat diet-induced inflammatory bowel disease by altering the gut microbiome - (https://www.sciencedirect.com/science/article/pii/S0955286322003229?via%3Dihub )
Excess dietary sugar alters colonocyte metabolism and impairs the proliferative response to damage - (https://pubmed.ncbi.nlm.nih.gov/37172822/ )

Source-Eurekalert