Non-Mucin-Degrading Bacterial Composition for Inflammatory Disease
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Solution Overview
Problem
Current treatments for inflammatory diseases such as graft-versus-host disease (GvHD) and inflammatory bowel diseases (IBD) have limitations, including high side effects and the need for additional preventive agents.
Innovation Solution
Compositions comprising non-mucin degrading bacteria, such as modified Bacteroides thetaiotaomicron strains with deleted polysaccharide utilization loci, are used to treat and prevent inflammatory diseases by outcompeting wild-type bacteria and maintaining intestinal health.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments (glucocorticoids, immunosuppressants) are used for GvHD and IBD, then disease severity is reduced, but side effects increase and quality of life deteriorates
Solution Approach 1:
The patent extracts and eliminates the harmful mucin-degrading function from Bacteroides thetaiotaomicron by deleting specific polysaccharide utilization loci (PULs), thereby removing the source of mucus layer degradation and inflammation while preserving beneficial bacterial functions
Solution Approach 2:
The patent modifies the functional parameters of Bacteroides thetaiotaomicron by altering its polysaccharide utilization capabilities through gene deletion, changing it from a mucin-degrading strain to a non-mucin-degrading strain that maintains intestinal mucus integrity
2Adaptability or versatility
If wild-type Bacteroides thetaiotaomicron is present in the gut, then bacterial diversity is maintained, but mucus layer degradation and inflammation occur
Solution Approach 1:
The patent removes the harmful mucin-degrading capability from Bacteroides thetaiotaomicron by deleting polysaccharide utilization loci, extracting the harmful function while preserving the beneficial presence of the bacterial species
Solution Approach 2:
The patent applies local quality modification by selectively deleting specific polysaccharide utilization loci (PULs) responsible for mucin degradation, thereby changing the local functional properties of the bacteria without eliminating the species entirely
3Reliability
If additional preventive agents are added to treat inflammatory diseases, then treatment coverage is improved, but treatment complexity and side effect profile increase
Solution Approach 1:
The patent creates a multi-functional therapeutic approach where a single modified bacterial strain (non-mucin degrading B. thetaiotaomicron) can treat multiple inflammatory conditions including GvHD and IBD, reducing the need for multiple specialized agents
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 non-mucin degrading bacteria effectively reduce inflammation with low side effects, improving survival rates and reducing disease severity in animal models of GvHD and IBD.
Implementation Method 1
The compositions exhibit low side effects and can be used in combination with existing treatments... the non-mucin degrading bacteria effectively reduce inflammation with low side effects, improving survival rates and reducing disease severity in animal models
Data Source
AI summary
Provided herein are compositions and methods for treating and/or preventing inflammatory disease. In particular, provided herein are non mucin degrading bacteria and their use in treating and/or preventing inflammatory disease (e.g., GvHD).