Craig Maynard, Ph.D., associate professor of Molecular and Cellular PathologyThe human intestine is home to trillions of microscopic organisms, including hundreds of species of bacteria. In most people, these bacteria coexist peacefully and contribute to a mutually beneficial relationship, with both human and bacteria deriving important benefits from the other. In certain individuals, specific bacteria are believed to provoke inflammation that characterize diseases such as Crohn’s disease.
“A very diverse set of gut bacteria can ‘swim’ through the layer of mucus that lines the intestines using specialized thread-like structures called flagella, the assembly and function of which involves a complex array of motility proteins,” said Craig Maynard, Ph.D., an associate professor in the University of Alabama at Birmingham Department of Pathology’s Division of Molecular and Cellular Pathology.
Among these motility proteins, flagellins, which are the basic building blocks of the flagella, are believed to be capable of inducing inflammatory responses seen in Crohn’s disease. It is still unclear specifically which flagellated bacteria drive gut inflammation, and whether there are specific features of their flagellins that underlie this potential.
Maynard recently published work in the journal Science Immunology, titled “Divergent immune responses to commensal bacteria bearing distinct motility signatures,” to investigate the distinct immune stimulatory functions of flagellated gut commensal bacteria.
In this study, analysis of more than 100 motile gut bacteria identified at least two highly distinct groups, which the authors refer to as G1 and G2 bacteria, based on the arrangement and diversity of specific motility genes.
The researchers examined mice in which the only bacteria in their intestines were three species of either G1 or G2 bacteria. In both sets of mice, the bacteria induced immune responses that favored their survival in the intestines. When the gut mucus barrier was breached, the G2 bacteria induced intestinal inflammation whereas the G1 bacteria did not.
Maynard explained that flagellins may be at least partially responsible for the pro-inflammatory capabilities of G2 bacteria.
“We identified a specific region of the flagellin proteins of select G1 and G2 bacteria that regulate their respective ability to stimulate the immune system,” Maynard said. “More broadly, we’ve identified multiple bacteria that are potentially capable of inducing intestinal inflammation, along with one flagellin-related mechanism that could underpin this function.”
Maynard is corresponding author on this study in collaboration with his group and that of Charles Elson, M.D., a professor in the Division of Gastroenterology and Hepatology. Other authors of the study include first author Lennard “Wayne” Duck, Katie Alexander and Qing Zhao, Division of Gastroenterology and Hepatology; Melissa Jennings, Jung-Shan Hsu, Covenant Adeboboye, Leighann Morgan, Kiarra Coger, Barbara Klocke and Goo Lee, Division of Molecular and Cellular Pathology; and Dave Hill and Alexander Rosenberg, Department of Biomedical Informatics and Data Science.
This work was supported by grants from the National Institutes of Health and the Crohn’s and Colitis Foundation and funding from the UAB Heersink School of Medicine Pittman Scholars Program.