Gut microbes key to foodborne pathogen infection

Whether or not you succumb to infection by Listeria monocytogenes could come down to what’s in your gut. New research published in mBio shows that germ-free mice are more susceptible to infection from the foodborne pathogen than mice with conventional intestinal microbiota.

In terms of infection, the results were unequivocal: 24 hours after infection, germ-free mice had 10,000 times more L. monocytogenes bacteria in their small intestines and about 1000 times more Listeria in their mesenteric lymph nodes than the conventional mice.

The authors also found that the expression of five intestinal microRNA (miRNA) molecules decreases in conventional mice upon Listeria infection, while it did not in germ-free mice - suggesting that gut microbiota may determine how the mouse genome expression is reprogrammed in the gut and how the animal responds to an infection.

“We were surprised by the robustness of the intestinal miRNA signature in germ-free mice and conventional mice,” said corresponding author Pascale Cossart of the Institut Pasteur in Paris.

The results show that even very small variations in miRNA expression can have important outcomes for the health of the animals, Cossart says.

While researchers have found a link between gut microbiota and an animal’s immune response, few studies have addressed the impact the microbiota has on miRNA expression during bacterial infections. Cossart and her colleagues approached the matter using the system they know best: Listeria infection.

Previous studies in Cossart’s lab have shown that during infection with Listeria, the bacterium and the host both reprogram their protein manufacturing using small non-coding RNA molecules like miRNA - pieces of genetic material that are used to selectively regulate the creation of proteins. Here, the researchers used conventional mice and germ-free mice to address the question of whether - and how - the gut microbiota has an effect on the course of infection and on the production of these regulatory miRNA molecules.

While differences in infection were clear, at the level of miRNA, the differences were not immediately evident: the most highly expressed miRNAs were produced at the same levels in both types of mice and they didn’t change much after infection. Nevertheless, the production of five miRNAs decreased after infection only in the conventional mice, indicating that the presence of the microbiota influences the level of miRNA expression.

“We found that even though the intestinal miRNA signature is globally stable, Listeria infection can affect the host miRNA response in a microbiota-dependent manner,” said Cossart. When paralleled with the lower susceptibility of the conventional mice to infection, these down-regulated regulatory molecules present an intriguing result, the authors say.

Cossart says that this study and others indicate that miRNA may be involved in protecting the host from infection, but their precise role isn’t yet clear. She notes that although this study was conducted in mice, miRNA and the protein coding gene targets they regulate may be very similar in mice and in humans. Cossart and her colleagues are planning to follow up on the work to try and figure out what impacts the changes in miRNA expression mean for the networks of protein-coding genes they regulate.