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A groundbreaking study using zebrafish has revealed that certain gut bacteria act as liver protectors by breaking down sorbitol, a sugar found in fruits and sugar-free products, before it can trigger fatty liver disease. When these protective bacteria are overwhelmed or absent, sorbitol travels to the liver where it converts to fructose and promotes dangerous fat accumulation.

What Happens When Protective Gut Bacteria Fail?

Researchers at Washington University in St. Louis discovered this protective mechanism by removing gut bacteria from adult zebrafish using antibiotics. Within just one week, the fish developed fatty liver disease even while eating normal diets. The culprit was sorbitol - a sugar naturally produced when the body breaks down glucose in the intestines.

"If you have the right bacteria, turns out, it doesn't matter," explained Gary Patti, PhD, the study's senior author and chemistry professor. "If you don't have the right bacteria, that's when it becomes problematic. Because in those conditions, sorbitol doesn't get degraded and as a result, it is passed on to the liver."

How Does Sorbitol Trigger Fatty Liver Disease?

When sorbitol reaches the liver unchecked, it undergoes a dangerous transformation. The liver converts sorbitol into fructose-1-phosphate, which then activates an enzyme called glucokinase. This enzyme promotes glucose breakdown for energy but ultimately increases fat production in the liver - the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects about 30% of adults.

The research team used sophisticated tracking techniques to follow sorbitol's journey through the body. They found that specific bacteria, particularly Aeromonas species, normally break down sorbitol in healthy gut environments. However, when these bacteria were absent or overwhelmed by excessive sorbitol intake, the sugar bypassed this protective barrier.

What Foods and Factors Increase Sorbitol Risk?

Sorbitol occurs naturally in many common foods and is widely used as an artificial sweetener. The study's findings suggest that excessive intake could pose risks for liver health, especially in people with compromised gut bacteria:

• Natural Sources: Apples, pears, and other fruits contain varying amounts of sorbitol that contribute to daily intake
• Artificial Products: Sugar-free gum, candy, and diet foods often use sorbitol as a primary sweetener
• Gut Health Status: People with disrupted gut bacteria from antibiotic use, illness, or poor diet may be more vulnerable to sorbitol's liver effects

The researchers demonstrated this risk by feeding zebrafish high levels of dietary sorbitol, which mimicked the effects of gut bacteria depletion and resulted in fatty liver disease development. Conversely, when they blocked sorbitol production using a drug called epalrestat, they prevented liver fat accumulation entirely.

Perhaps most encouragingly, the team found that reintroducing sorbitol-degrading bacteria into fish that had been treated with antibiotics successfully reversed fatty liver disease. This suggests that maintaining healthy gut bacteria populations could be a key strategy for liver protection.

"Our work identifies sorbitol metabolism in gut bacteria as a previously unknown factor that contributes to hepatic steatosis, thereby offering a potential target for microbiome-based strategies to treat MASLD," the researchers concluded.