St. Louis, Sept. 3, 1996 -- Researchers have discovered that bacteria that make their home in the gut have unsuspected powers of communication that can influence their environment.
A team at Washington University School of Medicine in St. Louis and the Karolinska Institute in Stockholm, Sweden, has developed a system for identifying the signals that normal bacterial inhabitants of the small intestine send to cells lining the gut. They identified one bacterial signal sender and discovered that the intestinal cells respond by making a favorite food for the microbe.
"These results provide insights about how we adapt to a microbial world and how microbes, in turn, may create a niche for themselves within a very complicated, dynamic and open ecological system," says Jeffrey I. Gordon, M.D., Alumni Professor and head of the Department of Molecular Biology and Pharmacology.
The findings are published in the September 6 issue of the journal Science. The first author is Lynn Bry, a graduate student in Gordon's laboratory.
"The findings illustrate that communication between the body and its resident bacteria is a lot more refined than we appreciated previously," says Per G. Falk, M.D., Ph.D., another author of the paper and a faculty member at both institutions. "By learning how normal bacteria can inhabit specific regions of the intestine, we may be able to prevent or treat infectious diseases. For example, the signaling molecules themselves may be useful for stabilizing the normal bacteria in the guts of patients with damaged immune systems or patients whose intestinal flora is disrupted by long-term use of antibiotics. We also might be able to use normal microbes as a new type of 'drug.' "
Before such "probiotics" enter the realm of possibility, scientists must learn more about the intestinal flora. More than 400 different microbial species make their home in the gut, and the number of individual microbes in this location is much greater than the number of cells in the human body. "There has been a lot of emphasis on the molecular basis of infectious diseases," Gordon says. "But little is understood about the bacteria that normally colonize humans and other mammals."
The researchers wondered whether bacteria that live in the gut influence the lives of intestinal cells, which undergo complex cycles of birth, maturation and death as the gut lining replaces itself every few days. Therefore, they raised mice in a totally germ-free environment or in an environment that contained the normal array of microbes.
The intestinal cells of the normal mice produced a constant supply of carbohydrates containing a sugar called fucose, a food source for many intestinal bacteria. The intestinal cells of the germ-free mice produced fucose-containing carbohydrates for three weeks after the animals were born and then quit. Adding gut bacteria from conventionally raised mice to adult germ-free animals caused the intestinal cells to start manufacturing the carbohydrates once again.
Having found that gut dwellers communicate with intestinal cells, the researchers honed in on Bacteroides thetaiotaomicron. This bacterium is a normal inhabitant of the distal portion of the small intestine and is known to scavenge fucose. "We wanted to identify a portion of the conversation we thought was occurring between the intestine's many bacterial inhabitants and its lining cells," Gordon says.
Bry found that the number of Bacteroides in the mouse intestine determined the extent to which the cells in the distal small intestine made fucose-containing carbohydrates. She also discovered that the bacterium manipulates the intestinal lining cells by remote control, not needing to attach to their surfaces. And when the researchers infected germ-free mice with a mutant strain of Bacteroides thetaiotaomicron that could not use fucose as a food source, the intestinal cells were unable to produce the fucose-containing carbohydrates. "Somehow, the bacterium's ability to use fucose is associated with its ability to direct production of fucose-containing carbohydrates in the intestinal lining cells," Gordon says.
Gordon speculates that this knack may help create a niche for other microbes. "It may allow several species of fucose-using bacteria to live in symbiosis with one another," he says. "But fucose often is used by pathogens. So the ability of some normal gut bacteria to direct production of fucose in intestinal cells may allow beneficial bacteria to prosper, leaving no room for bacteria that cause disease. We are testing this idea by adding various combinations of normal or disease-producing bacteria to the intestines of germ-free mice."