Gut microbial utilization of the alternative sweetener, D-allulose, via AlsE

Which Gut Bacteria Can Ferment Allulose? Very Few

A study in Communications Biology screened 85,202 bacterial genomes and found the enzyme that metabolizes allulose — AlsE — in just 116 species. Only about 15.8% of healthy human gut metagenomes carry the gene.

That is the most complete answer yet to a question formulators hear constantly: what actually happens to allulose in the gut?

The Question, in Plain Terms

Allulose is poorly absorbed in the small intestine. Whatever reaches the colon becomes food for bacteria. How much fermentation happens, and which bacteria do it, decides whether allulose causes gas and bloating (like many sugar alcohols) or passes through comfortably.

Before this study, the microbial ecology of allulose was essentially a black box. AlsE — D-allulose-6-phosphate 3-epimerase — was known from a handful of lab strains. Nobody had surveyed how common allulose-fermenting bacteria really are.

How They Checked

Three steps:

1. Genome screen. The authors searched 85,202 bacterial genomes for AlsE homologs — the broadest phylogenetic survey of allulose metabolism yet.
2. Human gut metagenomes. They looked at 3,079 healthy human gut metagenomes to estimate how common allulose-fermentation capability is in real populations.
3. Lab validation. In-silico candidates were grown in culture to confirm actual allulose metabolism.

What They Found

AlsE Is Phylogenetically Rare

116 of 85,202 genomes carried AlsE. Allulose fermentation is an unusual trait, not a common one.

Most People's Microbiomes Cannot Ferment Allulose

Only ~15.8% of the 3,079 human gut metagenomes contained alsE. For roughly 84% of people, allulose is not meaningfully fermented by their gut bacteria.

One Species Confirmed in the Lab

Clostridium innocuum metabolized allulose through AlsE in culture. Notably, E. coli carrying alsE could not grow on allulose as the sole carbon source without heterologous overexpression — having the gene is necessary but not sufficient for allulose utilization.

What This Explains About Digestive Comfort

Sugar alcohols like sorbitol and maltitol are fermented rapidly and broadly by gut bacteria, producing gas. Allulose is fermented by very few species in most people. That limited fermentability:

• Reduces gas and bloating
• Explains allulose's better GI tolerance in human trials
• Backs clean-label and "digestive comfort" positioning

A Personal-Nutrition Angle

alsE presence varies between individuals, which raises a practical possibility: testing a person's gut metagenome could predict their individual response to allulose.

• People carrying allulose-fermenting bacteria → may experience some fermentation
• People without → allulose passes through essentially untouched

That positions allulose for microbiome-informed nutrition in a way most sweeteners cannot claim.

What It Means for Formulators

Consideration	Implication
GI tolerance claims	Genetic evidence for minimal fermentation in most people
vs. sugar alcohols	A clear tolerance differentiator from erythritol/sorbitol
Clean label	"Minimally metabolized" now has genomics behind it
Personalized nutrition	Future microbiome-testing angle
Regulatory	Supports digestibility discussions; claims still need human data

Worth being careful about one thing: the study does not say "never fermented." 15.8% of metagenomes did carry alsE. The accurate framing is "minimal fermentation for most people," not "zero fermentation for everyone."

Frequently Asked Questions

Q: Does allulose cause bloating? Human data generally shows good tolerance, with GI symptoms mostly at high doses. This genomics study explains why: most people's gut bacteria simply lack the enzyme to ferment allulose.

Q: Is allulose fermented like sugar alcohols? No. Sugar alcohols are broadly fermented, producing gas. Allulose is fermented by about 116 bacterial species found in ~15.8% of gut metagenomes — a dramatically smaller footprint.

Q: Can the microbiome adapt to ferment allulose? Possibly, but the trait is rare and species-specific. Testing individual response is the emerging approach.

Wrap-Up

This study answers the most common gut question about allulose at genome scale: very few bacteria can ferment it, most people's microbiomes cannot, and that is why it tends to be easy on the stomach. For the industry it strengthens clean-label, gut-friendly positioning — and opens a genuinely new angle in personalized nutrition.

Read the full paper: Communications Biology | DOI: 10.1038/s42003-025-07012-x