UC Davis researchers have identified changes in the gut microbiome that may result in 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 small amounts cause digestive upset, a condition known as sorbitol intolerance.

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

“Our research shows that microbial sorbitol degradation normally protects the host from sorbitol intolerance. However, a defect in the microbial ability to break down sorbitol causes sorbitol intolerance,” said Ji Yun Li. said, first author of the study. Lee is an assistant project scientist in the UC Davis Department of Medical Microbiology and Immunology.

How oxygen levels in the gut affect microbes.

The researchers used metagenomic analysis to determine which gut bacteria have the 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 zero in on gut microbes belonging to the Clostridium class. Clostridium are anaerobic, meaning they do not like an oxygenated environment.

Researchers found that when mice were given antibiotics and fed a diet high in saturated fat, cells lining the intestines used less oxygen. This created higher oxygen levels in the gut, reducing clostridia. Without enough clostridia, sorbitol was not broken down in the gut.

The researchers conducted several experiments to try to restore the gut bacteria so that it could break down sorbitol again.

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

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

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

“This finding is significant given the prevalent use of sorbitol and similar sugar alcohols in the preparation of keto-friendly diet foods that are high in fat,” Lee said. “It also highlights the importance of oxygen consumption by the intestinal epithelial lining to maintain a healthy balance of intestinal bacteria, particularly clostridia, for proper digestion of certain sugars.”

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

“Our study provides a completely new starting point for methods of diagnosis, prevention and treatment of sorbitol intolerance,” said Andreas Bümler, senior author of the study. Bäumler is a distinguished professor and vice chair of research in the UC Davis Department of Medical Microbiology and Immunology.

Co-authors include Connor Tiffany, Scott Mahan, Andrew Rogers, Henry Nguyen and Hugo Masson of the UC Davis School of Medicine. Eric Stevens Sand Maria Marco of UC Davis; Matthew Calumand Emily A. Elo Fedrosch of Lawrence Berkeley National Laboratory; Kohei Yamazak of Kitasato University in Japan; and Peter Turnbaugh and Chan Zuckerberg Biohub of UC San Francisco (UCSF).