By Louise Kiru
Currently, 1.6 million Americans suffer from inflammatory bowel disease, a condition in which inflammation in the gut leads to diarrhea, abdominal pain, fever, and fatigue.
Bacteroides are a type of gut bacteria that have been implicated in inflammatory bowel disease. Their exact role is heavily debated—some species are believed to protect against disease, whereas others are suspected to increase risk. Now, scientists at Stanford have created a new tool to help resolve the debate. They have found a way to image individual Bacteroides species in the gut. Their paper appears in the April 20th edition of Cell.
Bacteroides are part of the normal gut microbiome and are the most abundant microbe found in people living in the United States. “Bacteroides are naturally occurring at high levels in the healthy gut and have co-evolved with humans,” said Elizabeth Stanley Shepherd, a co-author on the paper and a previous PhD student in Justin Sonnenburg’s lab. Sonnenburg is an associate professor of Microbiology and Immunology. Bacteroides help regulate a person’s immune system and energy production in exchange for a home. “They can sense, regulate and, respond to various states in the gut,” Shepherd said.
Inflammatory bowel disease occurs when a person’s immune system attacks the bacteria in the gut, resulting in damage to the gut lining. Scientists suspect that rearrangement of Bacteroides in the outer lining of the gut plays a role. Thus, tracking differences in where Bacteroides are located in the gut could lead to new treatments for inflammatory bowel disease. However, Bacteroides have been notoriously tricky to study until now, because scientists lacked the tools to track the locations of individual species.
Sonnenburg’s team found a way to differentiate individual species of Bacteroides by color coding them. The researchers inserted genes coding for fluorescent proteins, which emit light, into the Bacteroides. By using only two fluorescent proteins—green and red —they were able to image six different species of Bacteroides by varying the intensity of these two colors.
Sonnenburg’s team fed mice that were bred to lack gut bacteria with the six fluorescently labeled Bacteroides species and looked at images of the Bacteroides under a microscope. They found the Bacteroides species tended to settle near remnants of plant-based food that the mice had eaten. They also observed that several species were clustered together, while one or two were found in distinct regions of the gut. These are the first images showing the differences in the arrangement of various bacteroides species in the gut.
Sonnenburg’s color-coding method is an example of a synthetic biology tool. Synthetic biology is an evolving field that attempts to reprogram microbes and other natural biological systems. Sonnenburg’s team worked on Bacteroides, because there are few synthetic biology tools available for them and they may function as therapeutic vehicles that deliver anti-inflammatory drugs in the gut.