Figure 8.

Typical strategies used in engineering gut bacteria for precision medicine. (A) An overview of engineered bacteria used for sensing and responding to surrounding signals. After sensing surrounding signals such as pH and temperature, engineered bacteria can synthesize and release a series of molecules that can modulate the immune system, control pathogens, alter xenobiotic metabolism, etc. (B) Engineering gut bacteria to report transient molecules that can be easily degraded, absorbed or modified in the gut as surrogate biomarkers. (C) Precise depletion of gut bacteria by engineered phages. The specific targets for depletion can be undesirable genes or polymorphisms encoding drug metabolism enzymes. (D) Bacteria can be conferred with the ability to release therapeutic molecules or other abilities such as the ability to modulate the metabolism of drugs. (E) Biocontainment of engineered bacteria exemplified by auxotrophy, in which the number of engineered bacteria can be regulated by the nutrients supplied. Using these strategies alone or in combination, the level of drug metabolized by gut microbiota can be precisely regulated and thus the final drug response can be controlled.