Experts Assess Association of Recurrent Clostridioides Difficile with Gut Microbiota


Health-related quality of life scores were positively associated with log MHI and Bacteriodia, and negatively with Gammaproteobacteria and Bacilli.

Clostridioides difficile (C. diff) is defined as an anaerobic spore-producing bacteria that can infect the large intestine, causing diarrhea and colitis. Research has shown that in the recurring C. diff infection (rCDI), individuals experience a decrease in health-related quality of life (HRQL). In a study funded by Ferring Pharmaceuticals investigators evaluated the connection of the gut microbiome and HRQL among individuals with rCDI.

3D illustration of a clostridium difficile bacteria - Image credit: Gaetan |

Image credit: Gaetan |

The progressive condition of rCDI was related to high mortality rates, according to the study. Mortality rates were 39% higher for individuals with 3 or more recurrences of C. diff. The infected individuals HRQL was reported to be impacted due to the fear and concern of another future recurrence.

To mitigate the recurrence of rCDI, the researchers hypothesized that the gut microbiome had the ability to form resistance against C. diff and interrupt the gut-brain-axis that was linked to the sense of anxiety.

The researchers used data from Rebyota’s phase 3 PUNCH CD3 trail (NCT03244644). Patients included in the phase 3 study had both HRQL and microbiome data that was collected at baseline and weeks 1, 4, and 8.

The Clostridioides difficile Health-related Quality-of-Life Questionnaire (Cdiff32) was used to define the individuals’ HRQL. Prior to the calculation, the score was divided into 3 sections: physical, mental, and social. The researchers then collected stool samples from volunteers from the phase 3 trial, which helped measure the relative abundance of the gut microbiota.

The Microbiome Health Index (MHI) was analyzed with a binary indicator of MHI >7.2 defining a healthy microbiome. The Cdiff32 scores, microbiota data, and MHI > 7.2 were then projected using mixed effects analyses and scores were adjusted based on patient characteristics including sex, age, number of CDI episodes before treatment, treatment with fidaxomicin, proton pump inhibitor use, metabolism and nutrition disorders, surgical and medical procedures, infection and infestations, gastrointestinal disorders, and psychiatric disorders.

The results concluded that 176 individuals out of 262 had concurrent Cdiff32 and microbiome data. Among the other 176 individuals, 119 received fecal microbiota, live-jslm (RBL) and 57 received a placebo. The researchers reported that all the Cdiff32 scores were positively associated with log MHI and Bacteriodia, and negatively with Gammaproteobacteria and Bacilli.

“The most fascinating results for me from our manuscript…was that the patients that recurred with C. difficile but received RBL had absolute increases in their Cdiff32 scores whereas those that received placebo essentially did not,” said Paul Feuerstadt, MD, FACG, AGAF, from the Yale University School of Medicine. “It’s obvious that someone who does not recur would have an increase in their quality of life. So, this study works toward better correlating the changes in the microbiota and increases in Bacteroidia and Clostridia along with decreases in Bacilli and Gammaproteobacteria. This correlation is fascinating, since the cohort we used in the abstract included patients who either received RBL or placebo after standard of care antimicrobial. Therefore, we have a cleaner association between the microbiota changes and the Cdiff32 improvements.”

The researchers also found that the MHI healthy cutoff of 7.2 was linked with a 14.2- to 18.4-point increase on Cdiff32. The results could help create a shift toward healthier microbiota with its improvements for HRQL individuals that were diagnosed with rCDI. The findings could justify the HRQL advances found after receiving RBL.

“Ultimately, as clinicians, we treat patients, not diseases. C. difficile is an infection that does not simply cause changes in bowel habits and abdominal pains. We have shown that these changes in the microbiota seem to not only decrease the likelihood of a recurrence of C. difficile but also the improvements to the microbiota improve the patients social and psychological situations. Therefore, we are treating the entire person with this type of intervention, not just a disease,” said Feuerstadt.


Association Between Gut Microbiota and Health-Related Quality of Life in Patients with Recurrent Clostridioides difficile Infection: Results from the PUNCH CD3 Clinical Trial. Presented at: ID Week 2023. October 11-15, 2023.

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