B. Infantis H5 Cluster Composition for HMO Uptake and Gut Colonization
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Solution Overview
Problem
Existing microorganisms, such as B. bifidum, break down human milk oligosaccharides (HMOs) extracellularly, while B. longum subsp. infantis (B. infantis) can internalize and utilize them, but the specific genes responsible for this capability, particularly the H5 gene cluster, are not fully utilized in existing compositions.
Innovation Solution
A composition comprising Bifidobacterium longum subsp. infantis with a functional H5 gene cluster, including genes Blon_2175, Blon_2176, and Blon_2177, capable of internalizing and metabolizing LNB oligosaccharides, is formulated with specific concentrations and activation methods to enhance its binding affinity to mammalian mucosal cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If B. bifidum is used to break down HMOs, then extracellular breakdown occurs, but binding affinity to mucosal cells is reduced
Solution Approach 1:
The patent changes the biological parameters of the bacterium by selecting B. infantis with a functional H5 gene cluster and activating specific genes (Blon_2175, Blon_2176, Blon_2177) to simultaneously achieve extracellular HMO breakdown and high binding affinity to mucosal cells, resolving the contradiction between breakdown capability and binding affinity
2Productivity
If B. longum subsp. infantis is used to internalize HMOs, then utilization efficiency improves, but the H5 gene cluster functionality is not fully utilized in existing compositions
Solution Approach 1:
The patent performs preliminary activation of the H5 gene cluster in the B. infantis strain before administration, ensuring the bacterium is pre-equipped with full functionality to internalize and utilize HMOs efficiently upon reaching the infant gut
Solution Approach 2:
The activated B. infantis with functional H5 gene cluster autonomously internalizes and metabolizes LNB oligosaccharides in the infant gut, utilizing its own genetic machinery to convert HMOs into energy and growth substrates without requiring external enzymatic assistance
3Reliability
If B. infantis population is increased to improve gut colonization, then gastrointestinal health improves, but achieving sufficient population levels becomes difficult
Solution Approach 1:
The patent uses activated B. infantis with functional H5 gene cluster as an intermediary that preferentially consumes HMOs in the infant gut, creating a selective advantage that enables rapid population growth and effective colonization, achieving over 20% of total gut microbiome composition
Solution Approach 2:
The patent changes the competitive parameters of B. infantis by activating the H5 gene cluster, which enables the bacterium to efficiently utilize HMOs as a selective carbon source, thereby increasing its growth rate and population expansion capability in the infant gut environment
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 activated B. infantis with the H5 gene cluster effectively colonizes the infant gut, improving gastrointestinal health by increasing its population to over 20% of the total gut microbiome, reducing colic, and enhancing immune system development.
Implementation Method 1
an organism with a functional H5 cluster will transport and consume LNB oligosaccharides
Implementation Method 2
capable of hydrolyzing the internalized oligosaccharide
Implementation Method 3
Such Bifidobacterium will have a higher binding affinity to mammalian mucosal cells
Data Source
AI summary
Bifidobacterium longum subsp. infantis comprising a functional H5 cluster, including the Bifidobacterium longum subsp. infantis EVC001 deposited under ATCC Accession No. PTA-125180 may be used in compositions for improving gut health in infants and adults.