Escherichia coli is a type of bacteria that normally lives inside our intestines, where it helps the body break down and digest the food we eat. However, certain strains of E. coli are infectious. Many people are familiar with the negative side of E. coli. Now researchers at the Max von Pettenkofer-Institute at LMU Munich have demonstrated how benign strains of E. coli protect their hosts against infection by Salmonella. The researchers found that the composition of the microbiome determines whether E. coli can prevent infections by Salmonella strains.

Their findings are published in the journal Cell Host & Microbe in a paper titled, “E. coli enhance colonization resistance against Salmonella Typhimurium by competing for galactitol, a context-dependent limiting carbon source,” and led by Bärbel Stecher, professor of medical microbiology and hygiene at the Max von Pettenkofer-Institute at LMU Munich.

“The composition of intrinsic microbial communities determines if invading pathogens will find a suitable niche for colonization and cause infection or be eliminated,” the researchers wrote. “Here, we investigate how commensal E. coli mediate colonization resistance (CR) against Salmonella Typhimurium (S. Tm). Using synthetic bacterial communities, we show that the capacity of E. coli Mt1B1 to block S. Tm colonization depends on the microbial context.”

The researchers sought to determine what a healthy microbiome needs to effectively defeat an invasive pathogen. They investigated whether the bacterial species E. coli can provide protection against infection with human pathogenic Salmonella species.

“We discovered that, in particular, competition for a variety of sugars in the gastrointestinal tract can account for the failure of Salmonella to colonize the gut,” Stecher explained. In order to cause an infection, pathogenic bacteria must find an appropriate niche within the gut, which provides them with the carbon sources—such as certain sugars—that they need to replicate. However, competition for carbon sources in the gut is fierce. “If commensal E. coli consume all the sugar substrates, leaving nothing behind for Salmonella, the risk of infection is strongly decreased,” said Stecher.

The researchers found that if the complexity of the microbiome is too low, its members cannot consume all of the sugar substrates that Salmonella strains depend on.

“Using synthetic bacterial consortia, we were able to construct a model microbiome,” Stecher explained. This microbiome was made up of 12 bacterial species, all of which are found in the healthy murine gut. This combination of species was then introduced into germ-free mice, which were subsequently infected with xi. They discovered that, in the absence of Lachnospiraceae, E. coli was unable to prevent Salmonella infection. “This strengthens our conclusion that a combination of competition for carbon sources and complex interactions between bacterial species can protect the host against bacterial infections,” said Stecher.

The researchers are looking toward the future and hope they can translate these findings one day to humans. “At some point, our work could then help to develop treatments, such as probiotic bacterial cocktails that support the maintenance of a healthy microbiome,” concluded Stecher.