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

Summary

This study systematically mapped the AlsE enzyme (D-allulose-6-phosphate 3-epimerase) — the only known bacterial enzyme that metabolizes allulose — across 85,202 bacterial genomes. The enzyme was detected in only 116 bacterial species, and approximately 15.8% of healthy human gut metagenomes contained alsE. Clostridium innocuum was experimentally confirmed to metabolize allulose via AlsE, while E. coli possessing alsE could not grow on allulose alone. These findings suggest a strikingly limited gut microbial capacity to ferment allulose, supporting its favorable gastrointestinal tolerance profile.

Key Findings

• AlsE was identified in only 116 of 85,202 bacterial genomes screened — a remarkably narrow phylogenetic distribution.
• Only ~15.8% of 3,079 healthy human gut metagenomes carried alsE, meaning most individuals' microbiomes cannot efficiently ferment allulose.
• Clostridium innocuum was experimentally confirmed as an allulose-metabolizer via AlsE; E. coli with alsE did not grow on allulose as sole carbon source without heterologous overexpression.
• The limited fermentability supports allulose's low-calorie profile and explains its superior GI tolerance compared to sugar alcohols.
• The findings open a personalized nutrition angle: testing gut alsE could predict individual glycemic and digestive response to allulose.

Industry Relevance

This study directly addresses the most common consumer and regulatory question about allulose: "what happens in the gut?" The answer — minimal fermentation by most people's microbiome — reinforces allulose's safety and digestive comfort profile. For manufacturers, this peer-reviewed evidence supports clean-label communications around allulose's low digestibility and distinguishes it from sugar alcohols, which are broadly fermented and associated with bloating and GI distress.

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