Researchers in the Department of Biochemistry, Microbiology and Immunology have measured for the first time a key biochemical process occurring within the microbiome and pointed to roles it may play in human health. Protein lysine acetylation is a mechanism that regulates the function of bacteria, but it has never been studied directly in the gut microbiome community. Their paper was published this week in Nature Communications.
Using the platform they developed to measure this process, Dr. Xu Zhang in the labs of professors Alain Stintzi and Daniel Figeys, in collaboration with professor David Mack (Director of the CHEO Inflammatory Bowel Disease (IBD) Centre and a Senior Scientist at CHEO Research Institute), professor Jean-Francois Couture, and colleagues from Cell Signaling Technology Inc showed that lysine acetylation is widespread and abundant in our gut microbiome. In a demonstration of the platform’s potential, they also detected functional differences in the microbiome of those with Crohn’s disease compared with healthy participants.
“We saw that acetylation varies as a function of the disease, and therefore this acetylation might be a good target to manipulate the microbiome or manipulate the production of specific metabolites such as short-chain fatty acids,” says Dr. Stintzi.
Short-chain fatty acids are increasingly understood to be important for digestive health because, for example, they feed cells in the gut lining that maintain proper anaerobic conditions for a healthy microbiome, while keeping inflammation in check. Lysine acetylation is part of regulating the production process of these short-chain fatty acids, which include key gut fuels butyrate and acetate.
“If you look at ways of targeting short-chain fatty acid production of other metabolites, you might try to do it by increasing the levels of bacteria,” says Dr. Figeys. “But even if you increase the level of bacteria, if the regulation switch is set to ‘off’ instead of ‘on’, it doesn’t matter. So you also need to address the regulation.”
Dr. Figeys, Dr. Stintzi, and Dr. Mack have long found that they tend to gravitate toward similar research questions, and their labs have gradually become more integrated over the years, with students working side by side. It has transformed how they study IBD and led to numerous jointly-authored papers. One of the next steps in their quest for understanding will be to try to unpack the role of the gut environment—for example, changes in someone’s diet—on these functional processes, and the reciprocal role of those processes on the gut environment itself.
Image: Dr. Daniel Figeys