Scientists in France have demonstrated that the gut microbiome serves as an effective weapon in warding off disease microorganisms. The researchers published their study (“The Intestinal Microbiota Interferes with microRNA Response upon Oral Listeria Infection”) in mBio®.
The research reveals that germ-free mice are more susceptible to infection with the foodborne pathogen Listeria monocytogenes than mice with conventional intestinal microbiota. The authors were also able to show that expression of five intestinal microRNA (miRNA) molecules decreases in conventional mice upon Listeria infection while it did not in germ-free mice, indicating that the gut microbiota may determine, at least in part, how the mouse genome expression is reprogrammed in the gut and how the animal responds to an infection.
“While the crucial role of miRNAs in regulating the host response to bacterial infection is increasingly recognized, the involvement of the intestinal microbiota in the regulation of miRNA expression has not been explored in detail,” wrote the investigators. “We investigated the impact of the intestinal microbiota on the regulation of protein-coding genes and miRNA expression in a host infected by L. monocytogenes, a foodborne pathogen. We show that the microbiota interferes with the microRNA response upon oral Listeria infection and identify several protein-coding target genes whose expression correlates inversely with that of
the miRNA. Further investigations of the regulatory networks involving miR-143, miR-148a, miR-200b, miR-200c, and miR-378 will provide new insights into the impact of the intestinal microbiota on the host upon bacterial infection.”
“We were surprised by the robustness of the intestinal miRNA signature in germ-free mice and conventional mice,” says corresponding author Pascale Cossart, Ph.D., of the Institut Pasteur. “Our results show that even very small variations in miRNA expression can have important outcomes,” for the health of the animals.
Previous studies in Dr. Cossart’s lab have shown that during infection with Listeria, the bacterium and the host both reprogram their protein manufacturing using small noncoding RNA molecules like miRNA. 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.
When it comes to susceptibility to infection, the results were unequivocal: 24 hours after infection, germ-free mice harbored 10,000 times more L. monocytogenes bacteria in their small intestines and about 1,000 times more Listeria in their mesenteric lymph nodes than did the conventional mice.
Dr. 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.
The team is 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.