It is well-known that antibiotics can wreak havoc on our gut’s microbiome – and that antibiotic abuse risks the development of severe antibiotic-resistant strains of bacteria.
Now, new research using computational models shows that a common diarrhoea-inducing infection – typically caused by antibiotic abuse – can turn fatal in the presence of some strains of gut bacteria.
At a glance
CDI affects over 350,000 Americans a year. A fraction of these goes on to develop severe complications, sometimes leading to death. The infection poses the highest risk to the elderly and to those on long-term antibiotics. Moreover, one in six of those who develop it gets reinfected within eight weeks.
The new research from the University of Virginia School of Medicine and collaborators suggests that “opportunistic pathogens” in the gut that work in tandem may provide insight into why some individuals are at particular risk for severe CDI.
The perfect storm
CDI by itself usually triggers a bout of diarrhoea, the subsequent dehydration that follows, abdominal pain and fever. It is usually experienced in hospital settings, often due to antibiotics weakening the ability for helpful bacteria to thrive and encouraging the growth of pathogens like C. difficile. However, this is not always the case.
The researchers found that a group of antibiotic-resistant opportunistic pathogens called enterococci can make C. difficile more potent and dangerous. Enterococci are bacteria that can cause dangerous infections on their own, such as meningitis, urinary tract infections, diverticulitis, and other conditions.
However, the researchers found that the threat they pose does not end there. Enterococci produce amino acids, including leucine and ornithine, which make C. difficile a more potent threat for people whose gut compositions have been disrupted by antibiotics.
The research team collected stool samples of those with CDI from the Vanderbilt University Medical Center, Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania. They then used a combination of lab tests and advanced computer modelling to better understand how C. difficile interacts with other microorganisms in the gut.
They found that enterococci can dramatically reshape the gut’s metabolites to create a conducive environment for C difficile, in turn, making the infection more potent. The enterococci produce amino acids including leucine and ornithine.
By better understanding how C. difficile interacts with enterococci and other microorganisms in the gut, doctors will be better positioned to battle this common and serious infection. Jason Papin, PhD, of UVA’s Department of Biomedical Engineering and lead researcher on the study, says, “With this greater understanding, we have an opportunity to develop new therapeutic strategies to treat this dangerous infection.”
Understanding the complex interactions between C. difficile, other microbes, and the human gut requires expertise from a multidisciplinary team across several institutions. “The computational modelling that Matthew Jenior [UVA postdoctoral fellow in the Papin lab] performed was instrumental in discovering the role of amino acids in the interaction between C. diff and enterococci,” Papin adds.
The study, published in Nature, could lead to better ways of identifying individuals at risk for severe C. difficile infections and pave the way for new treatments. By gaining a greater understanding of the interactions between microorganisms in the gut, doctors may be able to combat this dangerous infection more effectively.