Oral microbiota therapy rebuilds gut bacteria to prevent recurrent C. difficile infection

10.04.2026

VOS, an FDA-approved oral microbiota therapy, has been shown to reduce infection risk compared to traditional fecal transplants.

What is already known

Disruptions to the gut microbiota—caused, for example, by antibiotic treatment—can drive recurrent C. difficile infection. Previous studies using fecal microbiota transplants and microbiota-based therapies suggest that restoring gut bacteria could prevent recurrence, but it’s unclear which specific bacterial species or metabolites are most important.

What this research adds

Researchers conducted a clinical trial testing VOS, an oral microbiota therapy made of purified Firmicutes spores, in people with recurrent C. difficile infection, collecting stool samples before and after treatment to track bacterial colonization and changes in gut metabolites. VOS restored beneficial bacteria and increased secondary bile acids and short- and medium-chain fatty acids, creating a gut environment that inhibits C. difficile growth.

Conclusions

The findings suggest that VOS is safe and effective at reducing recurrence of C. difficile infection.

Disruptions to the gut microbiota—caused, for example, by antibiotic treatment—can drive recurrent C. difficile infection. Now, researchers have found that an oral microbiota therapy made of purified bacterial spores can prevent these infections by rebuilding a healthy gut microbiota and its protective metabolites.

The findings, published in Nature Medicine, suggest that the therapy is safe and effective at reducing recurrence of C. difficile infection.

Previous studies using fecal microbiota transplants and microbiota-based therapies suggest that restoring gut bacteria could prevent recurrent C. difficile infection. In particular, VOS—an FDA-approved oral microbiota therapy, made of purified Firmicutes spores from healthy donors—has been shown to reduce infection risk compared to traditional fecal transplants.

However, it’s unclear which specific bacterial species or metabolites are most important, and how VOS prevents recurrent C. difficile infection at a mechanistic level. So, Jessica Bryant at Seres Therapeutics in Cambridge, Massachusetts, and her colleagues conducted a clinical trial testing VOS in people with recurrent C. difficile infection.

Restoring the microbiota

The researchers gave either VOS bacteria or a placebo to 182 people who had recently taken the antibiotic vancomycin and had at least three C. difficile infection. Stool samples were collected before and after treatment to track how VOS bacteria colonized the gut.

Compared with people receiving the placebo, those who received VOS had more beneficial bacterial species appear in their guts, with more protective Firmicutes and fewer Proteobacteria and other disease-associated species. These bacteria stayed in the participants’ guts for at least 24 weeks, the researchers found.

In contrast, people on the placebo had slower and incomplete microbiota recovery, with fewer beneficial bacteria and more harmful species persisting in their guts. Participants who received VOS did not report significant side effects compared to those receiving the placebo.

Preventing recurrence

Before VOS treatment, participants had high levels of primary bile acids and low levels of protective secondary bile acids, a pattern that favors C. difficile growth. After VOS treatment, secondary bile acids and beneficial fatty acids increased rapidly, while primary bile acids decreased.

Laboratory tests confirmed that these fatty acids can slow or stop C. difficile growth. Similar changes were also produced by VOS bacterial spores outside the body, suggesting that the treatment restores gut metabolites that help block infection, the authors say.“These data support a potential role for VOS, after antibiotic therapy, to restore the microbe-associated metabolic functions needed to prevent [C. difficile infection] recurrence.”