Ingestible optoelectronic capsules enable bidirectional communication with engineered microbes for controllable therapeutic interventions.

Engineered microbes can be used for biomolecular sensing and therapeutic interventions. However, they cannot be monitored and controlled while in vivo. Here we combine optogenetically engineered Escherichia coli Nissle 1917, an ingestible optoelectronic capsule and a wireless smartphone to establish a bidirectional biological-optical-electronic signal processing chain for diagnostic or therapeutic capabilities under user control. As a proof of concept, we engineered E. coli Nissle 1917 to detect inflammation-associated nitric oxide in the pig gut and generate a bioluminescent signal for diagnosis of colitis. This signal is transduced by the optoelectronic capsule into a wireless electrical signal and remotely monitored by a smartphone. Smartphone wireless signals activate LED irradiation in the optoelectronic capsule, in turn activating the microbial expression and secretion of an anti-inflammatory nanobody to alleviate colitis in pigs. This approach highlights the potential for integrating synthetic biology and optoelectronics for digital health monitoring and controllable intervention.