Synthetic HMO Composition for FUT2 Non-Secretor Microbiota Modulation
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Solution Overview
Problem
There is a need to effectively increase the abundance of Bifidobacterium adolescentis and/or B. pseudocatenulatum in the gastrointestinal tracts of humans carrying the human fucosyltransferase 2 (FUT2) genetic mutation, as these individuals have reduced levels of these beneficial bacteria, which can lead to impaired gut barrier function and inflammatory responses.
Innovation Solution
Administration of fucosylated human milk oligosaccharides (HMOs), such as 2′-FL, 3-FL, DFL, or LNFP-I, either alone or in combination with non-fucosylated HMOs like LNnT, to promote the growth and relative abundance of Bifidobacterium adolescentis and/or B. pseudocatenulatum, thereby modulating the intestinal microbiota and improving gut health.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fucosylated HMOs are administered to increase bifidobacteria abundance, then gut barrier function and microbial community are improved, but the solution requires specific genetic knowledge (FUT2 status) and targeted composition formulation
Solution Approach 1:
The patent applies local quality by tailoring the HMO composition specifically to individuals with FUT2 non-secretor status. The composition contains fucosylated HMOs in specific amounts (0.1-10g/day) that are selectively beneficial for this genetic subgroup, while non-secretors receive higher amounts of fucosylated HMOs compared to secretors. This personalized approach optimizes gut barrier function and bifidobacteria abundance specifically for those who need it most.
Solution Approach 2:
The patent utilizes parameter changes by adjusting the concentration and type of HMOs based on FUT2 genetic status. The composition specifies different amounts of fucosylated HMOs (such as 2'-FL, 3-FL, DFL, LNFP-I) versus non-fucosylated HMOs (such as LNT, LNnT) depending on the individual's secretor status. This parameter adjustment ensures optimal bifidobacteria modulation while accounting for genetic variability in fucosyltransferase activity.
2Quantity of substance
If HMOs are used to selectively stimulate bifidobacteria growth, then beneficial bacterial abundance increases, but the effectiveness is reduced in individuals with FUT2 genetic mutation
Solution Approach 1:
The patent converts the harmful effect of FUT2 mutation (reduced ability to produce fucosylated HMOs endogenously) into a benefit by providing exogenous fucosylated HMOs in the composition. Non-secretor individuals who cannot produce fucosylated HMOs themselves are given higher amounts of these compounds (0.1-10g/day), which directly compensate for their genetic deficiency and enable effective bifidobacteria stimulation despite their genetic status.
Solution Approach 2:
The patent uses fucosylated HMOs as intermediaries to bridge the gap caused by FUT2 mutation. These exogenous fucosylated HMOs serve as the missing link that non-secretor individuals cannot produce themselves, enabling the selective stimulation of bifidobacteria growth. The composition acts as a mediator that delivers the necessary fucosylated compounds directly to the gut microbiota, bypassing the defective endogenous production pathway.
3Ease of manufacture
If a standardized HMO composition is used for all individuals, then manufacturing is simplified, but it fails to account for genetic variations in HMO metabolism
Solution Approach 1:
The patent achieves universality by creating a composition that serves multiple functions for different genetic groups within a single product formulation. The composition contains both fucosylated HMOs (2'-FL, 3-FL, DFL, LNFP-I) and non-fucosylated HMOs (LNT, LNnT) in specific ratios, making it universally applicable to both secretors and non-secretors while optimizing benefits for each group. This multi-functional approach eliminates the need for completely separate products for different genetic types.
Solution Approach 2:
The patent applies segmentation by dividing the HMO composition into distinct functional components: fucosylated HMOs (0.1-10g/day) that target bifidobacteria in non-secretors, and non-fucosylated HMOs (0.1-5g/day) that provide additional prebiotic benefits. This segmented approach allows the single composition to address different metabolic pathways and genetic variations, providing personalized nutrition within a standardized product framework.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The administration of fucosylated HMOs increases the abundance of Bifidobacterium adolescentis and/or B. pseudocatenulatum, creating a more benign intestinal microbial community, reducing pathogenic infections, improving gut barrier function, and modulating inflammatory responses, thus preventing conditions like type 2 diabetes and gastrointestinal inflammation.
Implementation Method 1
Because some bacteria are able to produce a large selection of carbohydrate active enzymes (such as glycoside-hydrolases and transporters), the bacteria can grow on carbon sources, which may be less easily used by other members of the intestinal microbial community.
Data Source
AI summary
A method and composition including an effective amount of one or more synthetic neutral HMOs are disclosed for modulating the microbiota in the gastro-intestinal tracts of non-infant humans who are carriers of the human fucosyltransferase 2 (FUT2) genetic mutation and for improving one or more gastrointestinal conditions.