U.S. Department of Health and Human Services

“Friendly” Bacteria Compete with Disease causing Bacteria in the Intestine

In health, trillions of microbes (the microbiota) inhabiting the human gastrointestinal tract co-exist with their host in a relationship that is beneficial for both host and microbiota. However, when disease-causing (pathogenic) bacteria invade the gastrointestinal tract, they can disrupt this symbiotic relationship. Research scientists have recently uncovered important events that occur during pathogen infection. 
 
Certain types of E. coli bacteria cause severe diarrhea when they infect the intestine. In a study exploring the invasion of hosts by virulent bacteria, research scientists used mice that were infected with a type of bacteria that mimic human E. coli infection, as a model system of the infection process. Intestinal infection requires that the invading pathogen compete with resident bacteria of the gut for nutrients and space. The symbiotic residential bacteria, known as commensals, make their home in the surface layer of the intestine called the outer mucosa. When pathogens invade, they begin synthesizing and secreting virulence factors that disrupt the outer and inner mucus layers of the intestine. Burrowing through the damaged mucosa, the pathogens colonize the unoccupied niche of intestinal epithelial cells where they cause damage and inflammation. In this study, the researchers infected different groups of mice with the pathogenic bacteria; one group had been raised in the absence of normal bacteria (germ-free) prior to infection, and the other group had been conventionally raised. They found that the conventionally raised mice were able to clear the infection, but the mice raised germ-free were not. Also, analysis of pathogen virulence factors revealed that they are important in conventionally raised mice for the early stage of infection, but production of these factors diminished later in infection, forcing the pathogens from their cellular niche back into the intestine’s mucosa. There, the pathogens must compete with the commensals for a diet of simple sugars that they, the pathogens, require. However, in this environment the commensals tend to have the competitive advantage. Commensals that grow best on simple sugars successfully compete with the pathogens for this food. In fact, previous research found that infection by these pathogens alters the microbial community to promote growth of this type of commensals; the current study shows that these commensals then provide the benefit of devouring the food needed by the pathogens. Other types of commensals that are less picky about which sugars they will eat do not out-compete the pathogens when mice are fed a normal diet of multiple types of sugars, but when faced with a diet of only simple sugars, they too will compete for this food, starving the pathogens and clearing infection. The knowledge that infection and clearance of intestinal pathogens is the result of both expression of virulence factors and a competition for nutrients indicates that diet or probiotic approaches may be explored for future treatment of intestinal infections.

Kamada N, Kim Y-G, Sham HP, et al. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336:1325-1329, 2012.​