An engineered genetic circuit for lactose intolerance alleviation.

Area of Science:

• Biotechnology
• Synthetic Biology
• Microbiology

Background:

• Lactose malabsorption affects 68% globally, causing digestive distress.
• Current remedies focus on beta-galactosidase activity, overlooking colon pH drops from undigested lactose.
• Reduced colon pH impairs beta-galactosidase function and gut homeostasis.

Purpose of the Study:

• To develop a synthetic circuit for managing lactose intolerance.
• To engineer a system that maintains intestinal beta-galactosidase activity and colon pH.

Main Methods:

• Synthesized a tri-stable-switch circuit with dual functionality.
• Tested circuit efficiency in bacterial cultures across pH ranges.
• Evaluated circuit performance in a mouse model after lactose administration.

Main Results:

• The circuit demonstrated high beta-galactosidase activity and pH rescue capabilities.
• Functionality was confirmed in bacterial cultures and in vivo.
• The circuit prevented colon pH and beta-galactosidase activity drops post-lactose intake in mice.
• Observed impact on gut microbiota composition.

Conclusions:

• The tri-stable-switch circuit effectively stabilizes colon pH and beta-galactosidase activity.
• This engineered circuit shows promise as a prototype for lactose intolerance relief.
• The system's adaptability to environmental variations is key to its therapeutic potential.