Additional Glycosyl Hydrolase is Critical to Bacteria’s Ability to Consume HMOs

Abstract

Researchers at the University of California, Davis have developed technology that enables enhanced growth and colonization of beneficial gut bacteria through bacterial expression of heterologous alpha-fucosidases which target human milk oligosaccharides (HMOs), promoting a healthy gut microbiome.

Full Description

This invention provides compositions and methods involving beneficial gut bacteria, particularly strains of Bifidobacterium and Lactobacillus, engineered or selected to express heterologous alpha-fucosidases from glycoside hydrolase families GH-29 and GH-95. These enzymes enable bacteria to efficiently hydrolyze and metabolize fucosylated human milk oligosaccharides and related complex sugars resistant to digestion by the host. The approach promotes growth of these beneficial microbes in the gastrointestinal tract by utilizing HMOs as a carbon source, offering potential therapeutic and nutritional benefits especially in infants. Formulations can include these bacteria, alone or combined with HMOs or structurally similar oligosaccharides, administered via oral or rectal routes. This technology also encompasses methods to isolate and engineer strains with these enzymatic capabilities to selectively promote a health-supporting gut microbiome.

Applications

• Probiotic dietary supplements enriched with alpha-fucosidase-expressing beneficial bacteria. 
• Infant formula supplemented with prebiotic human milk oligosaccharides and engineered probiotics. 
• Therapeutics for restoring healthy gut microbiota in infants, adults, and immunocompromised patients. 
• Functional foods and beverages incorporating synbiotic combinations. 
• Veterinary applications supporting gut health in livestock using tailored probiotic strains. 
• Microbiome modulation products for managing digestive disorders, allergies, or metabolic diseases. 
• Research tools for isolating and characterizing beneficial gut bacteria with enhanced carbohydrate. metabolism

Features/Benefits

• Enables selective growth of beneficial bacteria on complex oligosaccharides indigestible by the host. 
• Supports establishment and maintenance of a healthy gut microbiota, particularly in breast-fed infants. 
• Increases consumption and metabolism of fucosylated human milk oligosaccharides. 
• Utilizes engineered or naturally occurring bacterial strains expressing GH-29 and/or GH-95 alpha-fucosidases. 
• Compatible with oligosaccharide supplementation to synergistically promote gut health. 
• Applicable to various delivery methods including oral and rectal administration. 
• Potential to reduce pathogenic bacterial colonization by competitive exclusion. 
• Broad applicability across Lactobacillus and Bifidobacterium strains with beneficial gut properties.

Patent Status