Researchers think they know why sugar-free candy and gum give some people gas

Researchers at UC Davis have identified changes in the gut microbiome that may lead to an inability to digest sorbitol. Sorbitol, a sugar alcohol, is used in sugar-free gum, mints, candies and other products. It is also found naturally in apricots, apples, pears, avocados and other foods. At high levels, sorbitol can cause bloating, cramping, and diarrhea. For some people, even a small amount causes digestive upset, a condition known as sorbitol intolerance.

A new study in mice found that taking antibiotics, combined with a high-fat diet, reduced the number of Clostridia gut microbes, which can break down sorbitol. The results were published in the journal Cell.

“Our research suggests that microbial breakdown of sorbitol normally protects the host against sorbitol intolerance. However, impaired microbial ability to break down sorbitol causes sorbitol intolerance,” said first author Jee-Yon Lee. of the study. Lee is an assistant research scientist in the Department of Medical Microbiology and Immunology at UC Davis.

How Oxygen Levels in the Gut Affect Microbes

The researchers used metagenomic analysis to identify which gut bacteria have genes that make the enzyme that breaks down sorbitol. They also identified which of these gut bacteria were abundant before – but not after – antibiotic treatment.

This analysis allowed them to focus on gut microbes belonging to the Clostridium class. Clostridium are anaerobic, meaning they do not like environments containing oxygen.

Researchers found that after receiving antibiotics and a diet high in saturated fat, the cells lining the intestine used less oxygen. This created a higher level of oxygen in the intestine, thereby reducing Clostridia. Without enough Clostridia, sorbitol was not broken down in the intestine.

Researchers performed several experiments to try to restore gut bacteria so they could break down sorbitol again.

In one, they fed mice Anaerostipes caccae, a gut bacteria that produces butyrate. Butyrate is a short-chain fatty acid produced as part of the normal fermentation process in the intestine. It improves the use of oxygen by the cells lining the intestine, the epithelial lining, which reduces oxygen levels in the large intestine.

Regulating oxygen levels with Anaerostipes caccae restored normal levels of Clostridia, which protected mice from sorbitol-induced diarrhea, even after butyrate-producing bacteria were cleared from the mouse digestive system.

Researchers suggest that a drug used to treat ulcerative colitis, Crohn’s disease and other inflammatory bowel diseases, mesalazine (5-aminosalicylate), could be a treatment for sorbitol intolerance in man. Mesalazine, also known as mesalamine, works similarly to butyrate-producing bacteria, restoring the low oxygen levels in the gut favored by Clostridia.

“This finding is crucial, given the widespread use of sorbitol and similar sugar alcohols in the production of keto-friendly, high-fat health foods,” Lee said. “This also highlights the importance of oxygen consumption by the epithelial lining of the intestines to maintain a healthy balance of gut bacteria, particularly Clostridia, for proper digestion of certain sugars.”

An important limitation of the study is that mice can tolerate much higher levels of sorbitol than humans. Mice have a cecum, a pouch in their digestive system that slows the flow of intestinal contents and helps digest carbohydrates, which may help to better tolerate sorbitol. Clinical studies will be needed to test the hypothesis that mesalazine could treat sorbitol intolerance in humans.

“Our study provides a completely new starting point for approaches to diagnose, prevent and treat sorbitol intolerance,” said Andreas Bäumler, lead author of the study. Bäumler is a distinguished professor and vice chair for research in the Department of Medical Microbiology and Immunology at UC Davis.