Engineered Probiotics Sulfate Secondary Bile Acids
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Solution Overview
Problem
Current methods fail to effectively regulate unbalanced bile acid pools, leading to conditions such as intestinal and hepatic inflammation, cancer, and cirrhosis, due to the harmful effects of secondary bile acids like deoxycholic acid and lithocholic acid in the gastrointestinal tract.
Innovation Solution
A microbiome-based therapeutic composition comprising engineered probiotics, such as E. coli Nissle 1917 or Saccharomyces boulardii, expressing human sulfotransferase SULT2A1, which enhances sulfation of secondary bile acids in the gastrointestinal tract, thereby reducing their harmful effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If secondary bile acids are produced by microbial metabolism in the large intestine, then bile acid pools are formed for fat emulsification, but harmful effects occur including intestinal and hepatic inflammation, cancer, and cirrhosis
Solution Approach 1:
The patent converts the harmful secondary bile acids into beneficial sulfated derivatives by introducing sulfotransferase enzymes that catalyze the sulfation reaction, transforming toxic compounds into safe excretable forms while maintaining the bile acid pool's digestive function
Solution Approach 2:
The patent introduces sulfotransferase enzymes as intermediary catalysts that mediate the transformation of secondary bile acids into sulfated forms, enabling the conversion without directly exposing the host to toxic substances
2Reliability
If sulfotransferase is expressed in engineered probiotics, then sulfation of secondary bile acids is enhanced, but device complexity increases due to genetic engineering requirements
Solution Approach 1:
The patent enables the probiotic bacteria to self-produce the sulfotransferase enzyme through genetic engineering, allowing the system to autonomously perform the sulfation function without requiring external enzyme administration or complex delivery systems
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 therapeutic composition effectively regulates bile acid pools by increasing sulfation of secondary bile acids, preventing or treating disorders associated with unbalanced bile acid levels, including intestinal and hepatic diseases, and reducing carcinogenesis.
Implementation Method 1
Cytosolic sulfotransferases (SULTs) are responsible for the sulfation of small molecules such as neurotransmitters, steroids, xenobiotics, and bile acids.
Data Source
AI summary
The invention relates to a microbiome-based therapeutic composition comprising an engineered probiotic cell expressing a sulfotransferase and the use of the microbiome-based therapeutic composition in medicine and a therapeutic regimen.