Gut Bacteria Turned Into Sensors Read Changes in Intestinal Osmolarity

Acidity, oxygen and osmolarity in the gut change constantly, and these changes affect the makeup of the microbiome and disease. But there have been few ways to look at this environment without opening the gut. Researchers at the University of British Columbia in Canada reported in Cell a synthetic biology toolkit that turns bacteria living in the gut into measuring devices.

New genetic parts laid down for a commensal bacterium

The target is Bacteroides thetaiotaomicron, which is common in the human gut and relatively easy to genetically engineer. The researchers built four kinds of parts: a repressible promoter whose expression level can be tuned, a device that controls repressor activity at the DNA level, a modular fluorescent transcriptional reporter circuit, and an alternative integration pathway for putting plasmids into the chromosome.

Combining these parts, they designed a biosensor that detects the situation in which malabsorption raises gut osmolarity, and confirmed that it worked in test tubes and in a mouse model in which osmotic diarrhea was induced with a laxative. Fluorescence signals at the level of single bacteria could report gut osmolarity noninvasively over a long period.

Limitations

This is at the stage of mouse model and test tube validation, and safety and stability in the human gut have not been confirmed. Giving genetically modified bacteria to people requires a separate regulatory decision.