Scientists Find a Hidden Way a Popular Sugar Substitute Can Reach the Liver

A new study from Gary Patti's laboratory at Washington University in St. Louis, published in the journal Science Signaling, suggests that sorbitol, a sugar substitute widely used in low-calorie candy and chewing gum, may have metabolic effects that make it less harmless than commonly assumed. Patti, the Michael and Tana Powell Professor of Chemistry at WashU Medicine, has previously shown that the liver's processing of fructose can be exploited by cancer cells and contributes to steatotic liver disease, a condition involving excess fat in the liver that affects about 30% of adults worldwide. Patti describes sorbitol as being essentially 'one transformation away from fructose.'

Using zebrafish, the researchers traced how sorbitol moves through the body. They found it does not have to come directly from food: enzymes in the intestine can also produce it from glucose after a meal. Sorbitol production has historically been linked to diabetes, where high blood glucose drives the enzyme responsible for making it. But the zebrafish experiments showed that even under healthy conditions, glucose levels in the gut can rise high enough after eating to trigger significant sorbitol production.

The researchers found that certain gut bacteria, including sorbitol-degrading Aeromonas strains, can consume the sugar alcohol and convert it into a harmless byproduct before it travels further into the body. 'It can be produced in the body at significant levels,' Patti said. 'But if you have the right bacteria, turns out, it doesn't matter.' If those bacteria are absent or overwhelmed by a large sorbitol or glucose load, the compound is passed on to the liver, where it can be converted into a derivative of fructose.

The researchers found clear evidence that sorbitol does not necessarily stay confined to the digestive tract. 'We do absolutely see that sorbitol given to animals ends up in tissues all over the body,' Patti said. Patti's laboratory still needs to determine exactly how gut bacteria break down and remove sorbitol. Patti discovered the compound's prevalence firsthand after realizing that his own favorite protein bar contained a large amount of it.