Is Ulcerative Colitis an Energy Crisis in the Gut Lining?

Most diseases of the gut have been viewed through the lens of the immune system. In 1980, surgeon W.E.W. Roediger proposed something different and influential: that ulcerative colitis might be, at its root, an energy-deficiency disease of the cells lining the colon.

Butyrate: the colon’s preferred fuel

Roediger studied freshly isolated colon-lining cells from people undergoing surgery, comparing healthy tissue with tissue from patients who had ulcerative colitis. He measured how much energy the cells drew from different fuels — butyrate (a short-chain fatty acid made when gut bacteria ferment fiber), glucose and glutamine.

The findings were striking:

• In healthy colon, butyrate supplied roughly 75% of the cells’ energy — far more than glucose or glutamine. The colon lining is, in effect, fueled by the products of fiber fermentation.
• In ulcerative colitis, the cells’ ability to burn butyrate was significantly impaired, and the worse the disease, the greater the impairment.
• These cells weren’t simply dying — they compensated by burning more glucose and glutamine, showing the defect was specific to butyrate, not a general failure.

Why it changed the field

The “energy-deficiency hypothesis” turned attention to fuel and metabolism, not just immune attack. It made butyrate a central character in gut health and set the stage for later work showing that hydrogen sulfide from gut bacteria can be one of the things blocking butyrate use — linking diet, microbes and the colon lining in one story.

“[In ulcerative colitis] oxidation of butyrate to CO2 and ketones was significantly lower than in control tissues, and the decrease correlated with the state of disease.”

Decades later, the idea that a well-fed, fiber-fermenting gut keeps its lining energized remains one of the most replicated findings in colonic physiology.