H5-Competent B. Infantis Composition for Infant 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 current compositions, limiting their effectiveness in colonizing the infant gut.
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 mammalian mucosal cells is reduced
Solution Approach 1:
The patent changes the physiological state of B. infantis by activating the H5 gene cluster through exposure to HMOs during culture, transforming it from a dormant to an activated state. This parameter change enables the bacteria to develop high binding affinity to mammalian mucosal cells while maintaining the capability to metabolize HMOs, resolving the contradiction between breakdown capability and binding affinity.
2Adaptability or versatility
If B. longum subsp. infantis is used with H5 gene cluster, then internalization and utilization of HMOs is achieved, but colonization effectiveness is limited without proper activation
Solution Approach 1:
The patent applies preliminary action by activating the B. infantis strain with HMOs before administration to the infant. This pre-activation step ensures that the H5 gene cluster is fully induced and the bacteria are in an optimized state for colonization, thereby enhancing colonization effectiveness while maintaining HMO utilization capability.
Solution Approach 2:
The bacteria's H5 gene cluster enables them to self-activate when exposed to HMOs in the infant's gut. This self-service mechanism allows the bacteria to automatically induce their own metabolic pathways and binding proteins in response to the presence of their substrate, ensuring both HMO utilization and effective colonization without external intervention.
3Quantity of substance
If high concentration of B. infantis is administered, then gut microbiome population increases, but manufacturing and formulation complexity increases
Solution Approach 1:
The patent changes the physiological state of the bacteria from dormant to activated through HMO exposure during culture. This parameter change increases metabolic activity and binding affinity, allowing effective colonization at lower concentrations, thereby reducing formulation complexity while maintaining high bacterial population in the gut.
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
capable of internalizing and metabolizing LNB oligosaccharides
Implementation Method 2
enhance its 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.