Bile Acid-Modifying Bacterial Compositions for Metabolic Regulation
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Solution Overview
Problem
There is an unmet need to identify gut bacterial strains that regulate bile acids and salts and develop microbial therapeutics to treat metabolic disorders, as the mechanism by which these bacteria interact with the host to alter bile acid composition and function remains unclear.
Innovation Solution
Administering compositions comprising bacterial strains such as Turicibacter sanguinis, Escherichia coli, or Bacteroides thetaiotaomicron that express bile salt-regulating or bile acid-regulating genes, either naturally or through genetic engineering, to modulate bile acid metabolism and treat metabolic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional approaches are used to study bile acid regulation, then general knowledge about metabolism can be obtained, but specific identification of bacterial strains and mechanisms remains unclear
Solution Approach 1:
The patent segments the complex gut microbiota into specific bacterial strains (Turicibacter sanguinis, Escherichia coli, Bacteroides thetaiotaomicron) and further segments their functions by identifying specific genes (bsh, 7α-HSDH) responsible for bile acid regulation. This segmentation allows precise identification of strain-specific mechanisms while managing complexity through targeted gene analysis.
Solution Approach 2:
The patent applies parameter changes by genetically engineering bacterial strains to overexpress specific bile acid-regulating genes (bsh, 7α-HSDH). This changes the expression levels of key parameters (gene expression, enzyme activity) to achieve desired therapeutic effects on bile acid composition, thereby improving identification precision while managing developmental complexity through controlled genetic modification.
2Reliability
If bacterial strains are administered to regulate bile acids, then metabolic disorders can be treated, but the mechanism of interaction between bacteria and host remains unclear
Solution Approach 1:
The patent implements feedback mechanisms by measuring bile acid composition changes in host serum and feces after administering engineered bacterial strains. This feedback loop allows verification of treatment effectiveness while gathering data on host-bacteria interaction mechanisms, thereby maintaining reliability while reducing information loss about mechanistic details.
Solution Approach 2:
The patent uses bile acid composition as an intermediary marker to study host-bacteria interactions. By measuring changes in bile acid profiles (conjugated vs. unconjugated, specific isomers) as intermediary parameters, the patent can assess treatment effectiveness and infer interaction mechanisms without directly observing complex host-bacteria communications, thus maintaining reliability while managing information complexity.
3Productivity
If genetically engineered bacterial strains are used, then bile acid regulation can be enhanced, but the complexity of gene expression control increases
Solution Approach 1:
The patent extracts and isolates specific bile acid-regulating genes (bsh, 7α-HSDH) from complex bacterial genomes and transfers them into model organisms (E. coli, Bacteroides thetaiotaomicron). This extraction simplifies the genetic engineering system by focusing only on essential genes, thereby enhancing bile acid regulation efficiency while managing engineering complexity through targeted gene selection rather than whole-genome manipulation.
Solution Approach 2:
The patent achieves universality by using multiple bacterial hosts (E. coli, Bacteroides thetaiotaomicron, Turicibacter sanguinis) that can all perform the same bile acid-regulating function through expression of the same key genes (bsh, 7α-HSDH). This multi-functional approach enhances regulation efficiency through different delivery vehicles while managing genetic engineering complexity by using a standardized set of target genes across different organisms.
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 described methods effectively regulate bile salts and acids, thereby preventing or treating metabolic disorders by altering host lipid and steroid metabolism, demonstrating strain-dependent effects on fat tissue mass, lipid composition, and bile acid levels.
Implementation Method 1
bacterial strain that expresses a bile salt-regulating gene or bile acid-regulating gene
Implementation Method 2
genes encoding bile salt hydrolase or 7-alpha hydroxysteroid dehydrogenase
Implementation Method 3
genes encoding bile salt hydrolase
Implementation Method 4
genes encoding 7-alpha hydroxysteroid dehydrogenase
Implementation Method 5
depleting the gut microbiota of the subject (e.g., by administering antibiotics to the subject)
Data Source
AI summary
Provided herein are methods and compositions related to treating or preventing metabolic disorder.