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How changes in gut bacteria boost the growth of a common hospital-acquired infection

Nature study reveals shifts in the gastrointestinal metabolome that facilitate C. difficile infection

Antiobiotic-induced shifts in bacterial makeup allow C. difficile to grow.

Antibiotic-induced shifts in bacterial makeup allow C. difficile to grow.

One of the most common antibiotic-related illnesses, Clostridium difficile, also known as “C. diff,” poses a threat to thousands of Americans hospitalized each year. While most hospital-acquired infections are declining, C. diff is on the rise and causes diarrhea linked to 14,000 American deaths each year.

Major risk factors for getting this infection include staying in the hospital and taking antibiotics.

A new study by the University of Michigan Medical School reveals how antibiotics not only change the bacterial makeup of the gut but also foster the availability of metabolites, which C. difficile can use for germination and growth.

“The findings in our paper are not only vital to the development of new-targeted therapeutics for combatting C. difficile infection but could aid in understanding other gut inflammatory and metabolic diseases, including diabetes, obesity and inflammatory bowel disease, where changes in the gut microbiome could be intimately related to the chemical and nutrient environment,” says lead author Casey Theriot, Ph.D., Research Investigator in the Division of Infectious Diseases at the University of Michigan Medical School.

Antibiotic use destroys the good bacteria in people’s bodies that protect against illness and at leat temporarily disturb the normal balance in the intestinal tract. Researchers found that antibiotic administration resulted in distinct changes in the gastrointestinal microbiome and metabolome.

Researchers correlated specific alterations of the microbiome and metabolome to identify multiple states of the gastrointestinal ecosystem that were resistant to C. difficile infection. These states had distinct microbial community structures, but similar metabolic function.

The metabolic environment of the murine gastrointestinal tract after antibiotic treatment was enriched in primary bile acids and carbohydrates that supported germination and growth of C. difficile. While the findings resulted from animal studies, the study illustrates how the structure of the gut microbiome can shape function and, ultimately, influence disease outcome.

“These results underscore the importance of looking beyond microbiome community structure and measuring functional aspects when determining the relationship between the microbiome and human health and disease,” Theriot says.

Additional authors include  include Mark J. Koenigsknecht, Ph.D.; Paul E. Carlson Jr., Ph.D.; Gabrielle E. Hatton; Adam M. Nelson, Ph.D.; Bo Li; Gary B. Huffnagle, Ph.D.; Jun Z. Li, Ph.D.; and Vincent B. Young, M.D., PhD.

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