Understanding Prebiotics and Trehalose
To determine if trehalose is a prebiotic, we first need to define what a prebiotic is. According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), a prebiotic is a substrate that is selectively utilized by host microorganisms, conferring a health benefit. A key part of this definition is that the substance must reach the large intestine mostly undigested to be fermented by beneficial bacteria like Bifidobacteria and Lactobacilli.
Trehalose is a naturally occurring disaccharide, a sugar made of two glucose molecules joined by a specific α,α-1,1-glycosidic bond. While found in sources like mushrooms and yeast, it is also industrially produced and added to many processed foods due to its stability and preservative qualities.
The Role of Human Trehalase
The most significant factor differentiating trehalose from classic prebiotics is the human digestive system. Our small intestine produces an enzyme called trehalase, which efficiently and rapidly hydrolyzes trehalose into two glucose molecules. For most individuals, this process occurs so effectively that very little, if any, intact trehalose reaches the large intestine, where fermentation by gut bacteria takes place. This enzymatic breakdown means trehalose primarily functions as an energy source, similar to regular table sugar, rather than a selective food for gut microbes.
While this holds true for the majority, a small percentage of the population has a congenital trehalase deficiency. For these individuals, consuming trehalose can lead to gastrointestinal discomfort, such as bloating and diarrhea, because it passes undigested into the colon, where it is fermented indiscriminately by gut bacteria, much like lactose intolerance.
Trehalose and Specific Gut Microbes
Although oral trehalose is not a classic prebiotic for most people, its interaction with the gut microbiome is not nonexistent. It is known that certain strains of bacteria, including some pathogens, possess the enzymatic machinery (bacterial trehalase) to metabolize trehalose. The availability of trehalose as a carbon source in the gut can influence microbial populations and their metabolic pathways.
For example, some in vitro and animal studies have shown that certain lactic acid bacteria, like Lactococcus and Lactobacillus, can utilize trehalose, indicating a potential prebiotic-like effect for specific probiotic strains. Researchers have also investigated combining trehalose with probiotics, a concept known as synbiotics, to enhance the survival and activity of beneficial bacteria. However, these observed effects may not accurately reflect the complex conditions within the human gut.
The C. difficile Controversy
One of the most widely discussed aspects of trehalose's relationship with the gut microbiome involves the pathogenic bacterium Clostridioides difficile (C. difficile). In 2018, a study in mice suggested a link between increased dietary trehalose and the emergence of hypervirulent C. difficile strains (RT027 and RT078). These strains have unique genetic mutations allowing them to metabolize trehalose more efficiently, giving them a potential competitive advantage over other gut microbes, especially during or after antibiotic use. This report caused significant concern regarding trehalose consumption.
However, later research has challenged or provided a more nuanced view of this association. Other studies using human gut models or epidemiology have found no evidence linking dietary trehalose to the emergence of these strains or adverse patient outcomes, noting that other factors are likely more significant. The debate highlights the complexity of diet-microbe interactions and the need for more clinical data to draw definitive conclusions.
Bacteria that can utilize trehalose
- Beneficial Bacteria: Certain species of Lactobacillus, Lactococcus, and Bifidobacterium have been shown in some studies to ferment trehalose or be supported by it, particularly in synbiotic formulations.
- Pathogenic and Commensal Bacteria: The ability to metabolize trehalose is also found in other gut bacteria, including pathogenic and commensal species. This list includes:
- Clostridioides difficile: As noted, specific hypervirulent strains are more adept at using low concentrations of trehalose.
- Escherichia coli: Certain strains possess trehalase and can use trehalose as a carbon source.
- Blautia and Bacillus species: These genera contain species with trehalase enzymes capable of breaking down trehalose.
Trehalose vs. Traditional Prebiotics
| Feature | Trehalose | Traditional Prebiotics (e.g., FOS, GOS) |
|---|---|---|
| Classification | Disaccharide (two glucose units) | Non-digestible oligosaccharides or fibers |
| Absorption/Digestion | Rapidly hydrolyzed into glucose by human trehalase in the small intestine | Resistant to digestion in the small intestine, reaching the large intestine intact |
| Effect on Glycemia | Causes a milder and slower blood glucose rise compared to sucrose, but still impacts blood sugar | Does not raise blood glucose levels |
| Microbiome Impact | Interaction depends on specific bacterial strains with trehalase, and most is digested by human enzymes | Fermented selectively by beneficial bacteria like Bifidobacterium and Lactobacillus |
| Potential Risks | Controversial link to promoting virulent strains of C. difficile in some contexts | Generally safe, can cause gas and bloating at high doses |
| Primary Function | A low-glycemic sugar and cellular protectant | A selective substrate for beneficial gut microbes |
The Verdict and Future Outlook
So, is trehalose a prebiotic? For the vast majority of people with a functioning trehalase enzyme, it does not fit the classical definition of a prebiotic because it is absorbed as glucose in the small intestine and does not reach the colon to selectively ferment beneficial bacteria. However, its complex interactions with specific gut microbes, including potentially beneficial and harmful strains, mean it is not a simple inert sugar either.
While its status as a universal prebiotic is unfounded, research into trehalose is far from over. Studies are exploring trehalase-resistant analogues and synbiotics that could provide genuine prebiotic benefits. The controversy surrounding C. difficile highlights the need for careful consideration of how diet impacts the delicate balance of the gut microbiome. For consumers, the takeaway is that trehalose is not a replacement for proven dietary fibers that act as prebiotics. A healthy, fiber-rich diet remains the most reliable way to support a diverse and thriving gut microbiome.
Dietary Trehalose as a Bioactive Nutrient
Conclusion: Navigating the Trehalose Debate
In conclusion, trehalose's role in gut health is not what is typically defined as prebiotic. Its rapid digestion in the small intestine means it does not function like traditional prebiotic fibers. The interaction it has with the gut is more complex, involving specific bacterial strains and potential risks that are still under investigation. While research continues to uncover new facets of trehalose's effects on human health, relying on a balanced diet rich in fermentable fibers is the most reliable strategy for promoting beneficial gut bacteria and overall digestive health. Consumers should be mindful of the nuanced science and not equate trehalose with established prebiotic supplements or foods.
