What is already known
Enterobacteriaceae, a family of bacteria including Escherichia coli and Klebsiella pneumoniae, are often found at high levels in people with inflammatory bowel disease, where they exacerbate gut inflammation. Bile acids, which help digest fat, are known to influence influence bacterial colonization of the gut, and previous research suggests that an overgrowth of Enterobacteriaceae on the gut lining plays a role in inflammatory bowel disease. However, the role of bile acids in supporting the growth of Enterobacteriaceae remains unclear.
What this research adds
Researchers analyzed tissue samples from 70 people with Crohn’s disease and 30 healthy individuals, and found that while in healthy people most bile acids are absorbed in the small intestine, this process is altered in people with Crohn’s disease, leading to higher amounts of bile acids in the gut. Experiments in lab-grown cells and mice showed that bile acids disrupt the function of mitochondria in gut cells, leading to higher oxygen levels in the gut and creating an ideal environment for bacterial colonization.
Conclusions
The findings suggest that high levels of bile acids drive bacterial colonization of the gut and exacerbate gut inflammation by altering the intestinal environment.
Inflammatory bowel disease is a group of long-term conditions, including Crohn’s disease and ulcerative colitis, characterized by inflammation of the gastrointestinal tract. Researchers have now uncovered a link between bile acids and the growth of harmful bacteria in the gut in people with Crohn’s disease.
The findings, published in Science Signaling, suggest that high levels of bile acids drive bacterial colonization of the gut and exacerbate gut inflammation by altering the intestinal environment.
“This study establishes [bile acids] as a potential bridge that facilitates interactions between commensals and the host epithelium, laying the essential foundation for future investigations into various intestinal diseases,” the researchers say.
Enterobacteriaceae, a family of bacteria including Escherichia coli and Klebsiella pneumoniae, are often found at high levels in people with inflammatory bowel disease, where they exacerbate gut inflammation. Bile acids, which help digest fat, are known to influence influence bacterial colonization of the gut, and previous research suggests that an overgrowth of Enterobacteriaceae on the gut lining plays a role in inflammatory bowel disease. However, the role of bile acids in supporting the growth of Enterobacteriaceae remains unclear.
To study this further, Ravi Holani at the University of British Columbia in Vancouver, Canada, and his colleagues analyzed tissue samples from 70 people with Crohn’s disease and 30 healthy individuals.
Bacterial colonization
The researchers found that in healthy people, most bile acids are absorbed in the small intestine, but this process is altered in people with Crohn’s disease. In those who had undergone surgery to remove part of their gut, there was an increase in Enterobacteriaceae on the surface of the colon.
This increase was linked to higher gut levels of bile acids, in particular lithocholic acid (LCA), which boosted the bacteria’s ability to attach to gut cells.
Experiments in lab-grown cells showed that bile acids disrupt the function of mitochondria in gut cells, leading to the production of reactive oxygen species —harmful molecules that can damage cells. Indeed, gut cells showed a reduced ability to consume oxygen, leading to higher oxygen levels in the gut and creating an ideal environment for bacterial colonization.
Microbial overgrowth
Working in mice, the researchers found that higher bile acid levels resulted in an increase in oxygen levels in the gut and Enterobacteriaceae colonization. The higher oxygen availability in the gut gave these bacteria a competitive advantage and helped them to thrive, resulting in fewer diverse gut microbes and higher levels of Enterobacteriaceae.
Like in animal models, people with Crohn’s disease — especially those who had part of their gut surgically removed — had lower bacterial diversity in the gut and increased Enterobacteriaceae levels. This result suggests that the increased availability of bile acids in the gut contributes to the overgrowth of these bacteria.
“This identification of [bile acids] as facilitators of host-commensal interactions may be relevant to multiple intestinal diseases,” the authors say.
