Developing measure of signaling molecules of gut-brain communication

UNC Superfund Research Program’s Project 3 team is studying how arsenic exposure and the gut microbiome interact to cause diabetes. One challenge, according to Project leader Kun Lu, PhD, is this research requires the measurement of many signaling molecules, tryptophan metabolites and bacterial indole derivatives found in several different parts of the body that aid communication between the microbiome and the host. Most techniques only measure a few selected metabolites related to gut microbiome.

In March, the team published a paper detailing a new targeted metabolomics procedure for measuring 50 compounds related to microbiome-host communication. Dr. Lu said there isn’t another practice that can measure so many microbiome related compounds in one method.

The method incorporates mice brain, blood serum and fecal samples. With the new mass spectrometry procedure, Project 3 researchers can more easily get results needed for experiments to investigate whether and how the gut microbiome impacts body functions. Measuring these signaling molecules enables investigators to explore what role the nervous system in the gastrointestinal tract plays in the development of human disease, including diabetes.

Currently, the team is trying to demonstrate how arsenic exposure impairs host receptors via gut microbiome metabolites that regulate glucose through experiments using a mouse model.

Dr. Lu said the team also just started experimenting with interventions that affect the gut microbiome to protect against arsenic-induced diabetes. This research is rooted in two earlier studies published by Dr. Lu’s lab that found a diet of black raspberries positively impacted the gut microbiome by improving metabolism and vitamin synthesis.

“It’s documented that people exposed to inorganic arsenic develop diabetes. We think the gut microbiome plays a role in this process,” Dr. Lu said. “We also think the modulation of the gut microbiome can mediate the toxicity of inorganic arsenic.”

In the future, Project 3 plans to use the humanized mouse model developed by Project 1 leader Mirek Styblo, PhD. Dr. Lu said the mice he uses will also be germ-free, meaning that they don’t have any bacteria in their gut. With these mice, Dr. Lu and his team will be able to introduce selected gut bacteria to a mouse and then expose it to arsenic. Without the thousands of other bacteria in an average mouse’s gut, researchers can confirm that bacteria’s role in mediating arsenic toxicity in the body.