Phase 3 data link gut microbiome shifts to better mental health outcomes in patients treated with fecal microbiota, live-jslm.
A new analysis from a phase 3 clinical trial presented at this year’s Digestive Disease Week conference in San Diego, California, shows that a live biotherapeutic used to prevent recurrent Clostridioides difficile infection may also improve patients' mental quality of life, with outcomes correlating to shifts in the gut microbiome and metabolome.
Patients who received fecal microbiota, live-jslm, also known as RBL or Rebyota, were more likely to report improvements in mental health-related quality of life compared to those given placebo, according to exploratory data from the PUNCH CD3 trial. These benefits were observed even in some participants who experienced recurrence of infection.
“These findings are a stepping stone not only for understanding recurrent C. difficile but also for broader applications,” said Paul Feuerstadt, MD, FACG, AGAF, Associate Clinical Professor of Medicine at Yale School of Medicine and attending gastroenterologist at the PACT Gastroenterology Center. “If we can define what dysbiosis looks like for a given condition and what is missing in the microbiota, we could potentially alter a patient’s microbial composition to improve their physical and emotional health.”
Patient-reported outcomes were measured using the Cdiff32 questionnaire, a validated tool that evaluates physical, mental, and social impacts of infection. RBL responders showed more substantial improvements in mental domain scores than placebo responders. Some individuals in the RBL group who experienced recurrence still reported better mental health outcomes.
“We correlated these quality of life scores with microbiota changes using a method called multivariable recursive partitioning analysis,” Feuerstadt explained. “What we found was that patients felt better if they had increases in Bacteroides and Clostridia and decreases in Gammaproteobacteria and Bacilli.”
The microbiome and bile acid profiles were analyzed using genomic sequencing and liquid chromatography mass spectrometry. Participants who demonstrated increased levels of Clostridia and Bacteroidia, decreased levels of Gammaproteobacteria and Bacilli, and a shift toward secondary bile acids were more likely to report improved mental health scores.
“These microbiota shifts were directly associated with how patients felt physically, mentally, and socially,” Feuerstadt said. “For example, patients who were more comfortable going out in public without constantly searching for a bathroom were also the ones whose microbiota showed those beneficial changes.”
Feuerstadt added that the insights from this study may extend beyond infection management. “There may be a connection between microbiota and mood through the metabolome produced by gut organisms. By modifying the microbiota, we could influence people’s overall outlook and emotional well-being.”
He emphasized the two-pronged nature of C. difficile treatment, which requires both antimicrobials to control infection and microbiota restoration to prevent recurrence. “What is especially promising is that these microbiota changes also appear to improve quality of life. Being able to clinically correlate those changes with how patients feel opens up a fascinating area for future research.”
