Features of fecal microbiota at baseline and after antibiotic therapy may be predictive of recurrent Clostridiodes difficile infection in patients with and without ulcerative colitis (UC), according to study results published in Inflammatory Bowel Disease.
Previous research has suggested that disruptions to the gut microbiome contributes to inflammatory bowel disease, and that patients with UC are at particularly increased risk for C difficile infection. Therefore, through characterizing the fecal microbiota in patients with UC and/or C difficile infection, researchers conducted a single-center, prospective, observational cohort study to investigate whether fecal microbiota dynamics may predict future risk for recurrent C difficile infection and recurrent UC flare.
In total, 57 patients were enrolled across 3 cohorts: patients with symptomatic UC who tested positive for C difficile infection (cohort 1, n=32); patients without inflammatory bowel disease with symptomatic C difficile infection (cohort 2, n=14); and patients with UC flare without C difficile infection (cohort 3, n=11). Stool samples for cohorts 1 and 2 were collected at baseline, at the end of antibiotic treatment (14 days), and at the end of antibiotic treatment plus 14 days (approximately day 30). In cohort 3, stool samples were collected at baseline and day 30.
In total, 45.7% of patients (21 of 46) met the primary endpoint for recurrent C difficile infection; 34.4% (11 of 32) developed a subsequent UC flare. Among patients who developed a recurrent UC exacerbation, the median 6-point Mayo score was 4 and the median fecal calprotectin level was 383.5 µg/g.
A redundancy analysis was performed to assess differences in microbial communities using patients with recurrent C difficile and UC flare as variables. Significant differences were noted in the structure of the microbial community between patients who eventually developed recurrent vs nonrecurrent C difficile infections (P =.008). An evaluation of intraindividual community changes in the first 2 cohorts found that at the conclusion of antibiotic treatment, there were no differences in the Jensen-Shannon difference between patients with and without subsequent recurrent C difficile infections (P =.41).
Logistic regression analyses were performed to determine the baseline variables associated with the risk for recurrent C difficile infection (cohorts 1 and 2), while controlling for UC status (cohorts 1 and 3). Investigators found that female sex and a history of antibiotic use within the past year(odds ratios [OR], 2.5 and 3.3, respectively) were both associated with an increased risk for recurrent C difficile infection. Backwards stepwise regression demonstrated that 5 baseline variables were significantly associated with recurrent C difficile infection, even after adjusting for UC status: female sex was associated with an increased risk, while increased operational taxonomic unit richness and increased relative abundance of Enterobacteriaceae, Lachnospiraceae, and Veillonellaceae were considered protective.
Logistic regression analyses also indicated that the relative abundance of Gammaproteobacteria, Enterobacteriaceae, and Jensen-Shannon distance at day 30 were all associated with an increased risk for recurrent C difficile infection after controlling for UC status. Backwards stepwise regression found that female sex and an increased relative abundance of Ruminococcaceae (OR, 5.69 and 1.43, respectively) were associated with an increased risk for recurrent C difficile after adjusting for UC status.
Conversely, an increase in operational taxonomic unit richness and an increase in relative abundance of Faecalibacterium (OR, 0.83 per every increase of 10 taxa and OR, 0.47 per every 1% increase, respectively) were protective against recurrent C difficile infection.
Finally, investigators also found that prior hospitalization for UC within the past year, steroid use for initial UC treatment, and increased relative abundance of Bacteroidetes (OR, 16.0, 10.5, and 2.06 for every 10% increase, respectively) were associated with an increased risk for UC flares in cohort 1.
Study limitations included the small sample size, a small number of patients who developed a UC flare, only collecting fecal microbiota, and the collection of stool samples during the onset of either C difficile infection or UC flare, which may have affected microbial results.
“The novel ability to identify patients at high risk for [recurrent C difficile infection] with over 90% accuracy using a single stool sample…could affect future clinical decision making,” the researchers concluded. “Clinicians could utilize this microbial-derived information to escalate preventive therapy in higher-risk patients.”
The researchers emphasized that future studies should focus on the mechanisms of how shifts in gut microbiota may predispose patients to recurrent C difficile infection.
Lee AA, Rao K, Limsrivilai J, et al. Temporal gut microbial changes predict recurrent Clostridiodes Difficile infection in patients with and without ulcerative colitis [published online January 23, 2020]. Inflamm Bowel Dis. doi:10.1093/ibd/izz335