Infectious Diseases

January 28, 2026

Gut microbiome differs according to C. diff symptom status

In a study of children with symptomatic or asymptomatic C. diff, symptom status loomed as the strongest association with differences in gut microbial abundance and diversity.

Clostridium difficile bacterium, 3D illustration Illustration of C. diff bacterium. (iStock)

When an unfriendly germ moves in, sometimes symptomatic infection follows, sometimes not. A recent observational study at Vanderbilt Health examined gut microbes in 55 children sickened by the intestinal germ Clostridioides difficile, or C. diff, and 50 children colonized by C. diff who remained asymptomatic. The team had previously shown that toxins produced by the germ don’t differ meaningfully between infection and asymptomatic colonization in children.

But the microbiome does, the new study shows. Maribeth Nicholson, MD, MPH, associate professor of Pediatrics, Suman Das, PhD, research associate professor of Medicine in the Division of Infectious Diseases, and colleagues reported the study in The Journal of Infectious Diseases.

The Centers for Disease Control and Prevention estimates that C. diff sickens 500,000 people each year in the United States. A 2020 report in The New England Journal of Medicine estimated that the infection caused 20,500 in-hospital deaths in the U.S. in 2017.

In the new study, C. diff symptom status loomed as the strongest association with differences in gut microbial abundance and diversity, outweighing comorbidities and exposures to antibiotics, acid blockers, hospitalization and surgery. Children with symptomatic infection tended toward an imbalanced gut microbiome, with expansion of certain bacteria alongside depletion of others. The study also tracked butyrate and the gut bacteria that produce it through digestion of dietary fiber, finding these were significantly depleted in children with symptomatic infection when compared to those who remained asymptomatic. Butyrate provides fuel for the colon and vital regulation of gut health.

While the study couldn’t directly assess whether microbiome imbalance and butyrate depletion preceded symptomatic C. diff infection or resulted from it, the findings underscore growing interest in the roles of the gut microbiome and dietary fiber in C. diff outcomes.

Others on the study from Vanderbilt Health include Siyuan Ma, PhD, Britton Strickland, Mia Cecala, Lisa Zhang, Seth Reasoner, PhD, Matthew Munneke, Meghan Shilts, MS, and Eric Skaar, PhD, MPH. The study was funded by the National Institutes of Health under awards K23AI156132 and UL1TR002243.