Researchers at Rice University are putting bacteria to work as biosensors of gut inflammation.
Gut inflammation is believed to be linked to sulfur metabolism in the gut. Bacteria in the gut produce hydrogen sulfide, and the host’s cells detoxify it by converting it to thiosulfate and tetrathionate. Thus, an increase in these chemicals may signal the presence of gut inflammation.
Armed with this information, the group set out to engineer E. coli to sense thiosulfate and tetrathionate. To do this, they identified thiosulfate and tetrathionate sensors in the marine bacterium Shewanella (E. coli doesn’t naturally produce them). Then, they engineered a probiotic strain of E. coli to express these sensors and linked the whole process to the production of green fluorescent protein. That way, when E. coli senses thiosulfate or tetrathionate, it makes the fluorescent protein which is easily measured in the laboratory.
This study is actually quite remarkable. Previous studies used germ-free mice, or they tested sensors for substances that are not normally found in the gut. This study was performed in mice with an intact gut microbiome, and the sensor senses an actual, real-life gut metabolite.
The researchers tested their reporter strains in a mouse model of colitis. They treated the mice with dextran sulfate sodium (DSS) to induce colitis and administered the reporter bacteria to the mice by oral gavage. Six hours later, they collected feces and tissue samples from different parts of the colon.
The expression of the thiosulfate reporter was significantly higher in mice treated with DSS than in control mice. Importantly, the reporter expression in fecal samples was representative of expression from tissue samples. This means that fecal samples could be used in a noninvasive test for gut inflammation.
They also took a look at the gut tissue to verify that the DSS-treated mice actually had colitis. Indeed, the DSS-treated animals showed tissue pathology consistent with inflammation. Interestingly, the thiosulfate reporter was not induced in all of the mice with gut inflammation - the system isn’t quite ready for prime time.
The results were less promising for the tetrathionate reporter, however. The mice treated with DSS developed inflammation, but the signal from the tetrathionate reporter was very low. It’s possible that the reporter construct does not function very well in vivo.
Despite the less-than-stellar results, the authors are confident that they can (eventually) translate their findings to the real world. According to study author Jeffrey Tabor, “we'd like to develop a home inflammation test where a person prone to colitis flare-ups would eat yogurt that contained the engineered bacteria and see blue pigment in the toilet if they were sick."