Researchers have identified a new axis of host defense by studying what happens during enteric infection—a term that encompasses all types of intestinal infections including so called “stomach flu.” A new study from infectious disease investigators at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, uncovers how bile, a solution produced by the liver and responsible for the absorption of fat, plays a role in the fight against infections. While the study was conducted in mice, the researchers anticipate that the findings likely apply to humans as well. Results are published in Nature Microbiology.
“The changes we detected in the composition of bile with infection are beneficial for the intestine to clear infection,” said Matthew Waldor, MD, PhD, of the Brigham’s Division of Infectious Diseases. “Our findings reveal the intricate and dynamic nature of bile composition, shedding new light on the liver's critical role in defending the intestine from infection. These insights enhance our understanding of the liver's broader functions in regulating physiological stability and metabolic processes.”
While previous research on bile has focused on its function in the absorption of fats and other nutrients, there has been less of a focus on its composition, specifically during enteric infection. The researchers hypothesized that during infection, there is a shift in the composition and function of bile, given that it is an important part of communication between the liver and gut.
Using a mouse model, this study used global metabolic analysis to investigate changes in metabolites during an enteric infection. The mice were infected with one of two pathogens, L. monocytogenes, which replicates in the intestine, liver and gall bladder, or C. rodentium, which replicates in the caecum and colon. The different infection groups led to both shared and specific changes in bile metabolites. Moreover, hundreds of new metabolites that are in the bile metabolome were described. More specifically, the researchers found that enteric infection dynamically changes the composition of bile in order to provide intestinal defense. While these findings bridge a large gap in knowledge regarding bile composition, the researchers note that the 812 bile metabolites identified in this study likely only represent a subset of all bile metabolites. They predict that more will be discovered as tandem mass spectrometry techniques improve.
Authorship: In addition to Waldor, Mass General Brigham authors include Ting Zhang and Yuko Hasegawa.
Funding: Funding provided by the Massachusetts Host-Microbiome Center with funding from the NIH (P30DK034854), National Institutes of Health (R01AI042347) and the Howard Hughes Medical Institute.
Paper cited: Zhang T et al. “Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis” Nature Microbiologyl DOI: 10.1038/s41564-024-01862-z
