Fig. 1

The tri-stable-switch circuit can switch between two functionalities in response to environmental change. a The design diagram of the tri-stable switch circuit. Parts of the circuit are derived from the bacteriophage lambda. The two promoters, placm and patp2, were selected to respond to the lactose and pH signals, respectively. The placm promoter is triggered by lactose, and the patp2 promoter is weakened by the pH drop. b When BL21: pETDuet1-1 colonizes the colon with a neutral pH, lacZ is stably expressed, and β-galactosidase (β-GAL) accumulates intracellularly. c When a flux of unabsorbed lactose occurs in the colon, the system switches to a transition state in response to lactose and pH signals. The expression of ompA-lldD for L-lactate dehydrogenase (L-LDH) is strengthened, and the expression of lacZ is weakened. d The system then focuses on the expression of ompA-lldD. e The fermentation of lactose by the gut microbiota causes a pH drop, while expression of L-LDH transforms lactic acid into pyruvate, thus recovering the pH. The pyruvate then permeates into the cell for the tricarboxylic acid (TCA) cycle