Modified Bacterium Oxalate Degradation Gut Adaptation

The patent applies preliminary action by pre-adapting the E. coli Nissle 1917 bacterium to the gut environment through sequential passage in germ-free mice before introducing it to treat hyperoxaluria. This pre-adaptation ensures the bacterium maintains metabolic activity and oxalate degradation capability in the gut environment, resolving the contradiction between introducing therapeutic microbes and ensuring their survival and functionality.

The patent employs self-service by utilizing the bacterium's endogenous adhE gene and its natural ability to perform adaptive mutations in response to oxalate exposure. Rather than introducing complex exogenous pathways or multiple engineered components, the system allows the bacterium to self-modify and activate oxalate degradation capabilities through spontaneous mutations and selection pressure, thereby achieving high degradation efficiency without proportionally increasing developmental complexity.

The patent applies parameter changes by inducing specific mutations in the adhE gene under controlled conditions (sequential passage in germ-free mice, exposure to oxalate). These parameter changes in the bacterial genome enable the well-characterized E. coli Nissle 1917 strain to acquire oxalate degradation capability while maintaining its identity as a known and safe probiotic strain, thus resolving the contradiction between strain simplicity and functional capability.