Engineered Bile Salt Hydrolases and Derived Strains for Improved Gut Health

Background

Bile salts play critical roles in the human gastrointestinal tract, as influencers and modulators of the microbial composition throughout the gut. Bile salts are one of the primary components of bile, which is produced in the liver to aid in digestion of lipids. Gut microbiome bacterial species often express bile salt hydrolase (BSH) enzymes, which deconjugate bile acids. Deconjugation diminishes microbial toxicity of bile salts, and amino acids released during bile salt deconjugation can be utilized by bacteria as an energy source. Bacterial species with active BSH enzymes persist in the gut more effectively than species lacking BSH enzyme activity. BSH expression is common in probiotic lactobacilli.

Of note, various types of bile salts (conjugated, or not) comprise the bile salt intestinal pool, and this mixed composition influences the genera, species, and strains content of the large intestine microbiome. Consequently, several gut health attributes are directly and indirectly impacted by the bile salt composition in the human gut.

Technology Overview

Researchers from NC State University’s Departments of Food, Bioprocessing, and Nutrition Sciences and Population Health and Pathobiology have identified Lactobacillus-associated bile salt hydrolase (BSH) enzymes that modulate the gastrointestinal bile salt pool and shift the gut microbiome composition. With understanding of the influence of BSHs on the gut microbiome, the inventors have developed engineered Lactobacillus strains and BSHs. These strains differentially express BSHs to influence the composition of the gut microbiome. Changes to the bile salt pool can potentially impact human health through alteration of digestive functions and reduction of blood cholesterol. Shifts in gut microbiome composition can also prevent the onset or persistence of pathogenic gut microbes (e.g. C. difficile) and enhance the population of microbes with positive health effects. There are opportunities for utilizing the engineered strains and BSH enzymes to improve positive effects on human health, through treatment of metabolic diseases and other gut microbiome-associated diseases. (NCSU Ref. no. 19150)

Benefits

The engineered strains and BSH enzymes demonstrate the genetic and functional features of BSHs and the ability for modulating bile composition in vivo, which in turn can promote improved health and fend off infections.

Applications

Targeted engineering readily enables bile salt composition alteration to inhibit infectious disease (e.g. Clostridium difficile). It is a potential alternative to incumbent technologies such as fecal transplantation. Beyond infectious disease, microbiome alteration could also address metabolic diseases such as obesity, metabolic syndrome, and many other conditions.

Opportunity

NC State is currently seeking industry partners or licensees for the commercialization of this technology. There is strong potential for the commercialization of this technology to improve the composition of the bile salt pool for improve health outcomes.