Department of Health | HIV, STD, and TB Services | Congenital Syphilis

The Therapies That Could Shape The Future Of C Diff Treatment

Fecal microbiota transplantation has become one of the most effective treatments for recurrent Clostridioides difficile infections, but its long-term role in gastroenterology may hinge on moving beyond donor stool and toward microbiome-based therapies.

FMT involves transferring stool from a screened, healthy donor into the gut of a patient, to restore a healthy microbial community. For C. Diff — a bacterial infection that can cause severe diarrhea, colitis and even death — the therapy can break cycles of recurrence that antibiotics alone may not resolve. 

According to an article in Clinical Infectious Diseases, observational studies report cure rates exceeding 90% for C diff. However, clinical trials show substantially lower effectiveness — around 68% — highlighting that a significant portion of patients do not respond to FMT methods. 

"Twenty-five to 30% of people actually don't respond to this treatment modality," Krishna Rao, MD, an associate professor of internal medicine at the University of Michigan in Ann Arbor and co-founder and director of its FMT program, told Becker's. "To make progress, we need to know what's actually happening at a mechanistic level — why a healthy community resists C. Difficile while an unhealthy one doesn't — and how to convert an unhealthy community into one that has colonization resistance."

He noted that some case reports have shown patients improve even when donor stool is processed to remove bacteria, suggesting components such as bile acids, short-chain fatty acids or viruses may contribute to recovery.

The COVID-19 pandemic also reshaped FMT practice. When stool banks such as OpenBiome paused operations in 2020 to implement SARS-CoV-2 screening, Dr. Rao relied on vancomycin and fidaxomicin taper regimens, which worked for more than 90% of his recurrent C. Diff patients. FMT was reserved for the small subset who did not respond.

Looking ahead, Dr. Rao expects the field to shift toward precisely designed microbiome treatments made up of selected bacterial strains, each chosen for a specific purpose — for example, producing compounds that block C. Diff toxins. One example already in use is an FDA-approved, spore-based therapy.

"For C. Diff, FMT works, but it's barely working for anything else," he said. "To make progress in other microbiome-mediated conditions, we need rationally designed products with known mechanisms of action."

He also cited gut-specific beta-lactamase enzymes, which break down antibiotics in the gut before they harm beneficial bacteria, and monoclonal antibodies such as bezlotoxumab that target C. Diff toxins. 

But even effective products can face financial hurdles. Bezlotoxumab, for example, was approved by the FDA but recently pulled from the market.

"Even when you have something that's proven to work and saves lives, if the incentives aren't aligned, it can die on the vine," Dr. Rao said, noting that several gut-specific antibiotics and other candidates have failed despite strong clinical results.

Vedanta Biosciences Announces Phase 2 Study Of VE202 In Ulcerative Colitis Did Not Meet Primary Endpoint

VE202 was well tolerated, with no reports of treatment-related serious adverse events

Additional analyses from COLLECTiVE202 to be shared in upcoming scientific forums

Vedanta to focus resources on ongoing Phase 3 RESTORATiVE303 registrational study of VE303 in recurrent Clostridioides difficile infection

CAMBRIDGE, Mass., August 13, 2025--(BUSINESS WIRE)--Vedanta Biosciences, a late clinical-stage biopharmaceutical company developing microbiome-based oral therapies for gastrointestinal diseases, today announced that its candidate VE202 did not meet the primary endpoint of endoscopic response in the Phase 2 COLLECTiVE202 study for the treatment of patients with mild-to-moderate ulcerative colitis (UC).

"We are very disappointed that our study did not meet its efficacy endpoints, and our greatest regret is that people living with inflammatory bowel disease will not, for now, have the opportunity to benefit from a new treatment option," said Bernat Olle, Ph.D., Chief Executive Officer of Vedanta Biosciences. "The gut microbiome is a well-recognized driver of IBD, yet remains a facet of the disease untouched by current treatments. As a field, we have not yet succeeded in making a meaningful impact for people with IBD through microbiome-based approaches, but every study moves us closer to that goal. We are committed to sharing further analyses of this study at upcoming scientific meetings to help chart new paths forward."

"Our priority at Vedanta remains the successful execution of our ongoing global pivotal study of VE303 for the prevention of recurrent C. Difficile infection, with the goal of potentially delivering the first approved Live Biotherapeutic Product in any indication — and, in doing so, addressing a serious health condition with a significant unmet medical need," concluded Dr. Olle.

In the randomized, placebo-controlled COLLECTiVE202 study, endoscopic and clinical responses were assessed using standardized criteria, and the observed response rates in the VE202 group were not statistically different from those in the placebo group. VE202 was generally safe and well tolerated — most adverse events were mild or moderate in intensity, with no reports of treatment-related serious adverse events. Analyses of bacterial colonization, histological findings, and immune responses are ongoing and will be shared in future scientific forums.

Vedanta remains focused on advancing its other pipeline programs:

VE303: Vedanta is currently enrolling patients into RESTORATiVE303, a registrational Phase 3 study of VE303 for the prevention of recurrent C. Difficile infection (rCDI) at over 200 sites in 24 countries. The Phase 3 program is supported by results from a positive Phase 2 study, in which VE303 demonstrated potentially best-in-disease efficacy with a 30.5% absolute risk reduction compared with placebo and greater than 80% reduction in the odds of a CDI recurrence.

VE707: Vedanta is also advancing VE707 to prevent infections by multidrug-resistant organisms that affect a wide range of vulnerable populations in areas such as oncology, urology, transplantation, and critical care, with IND submission planned for 1H 2026.

Story Continues

About the COLLECTiVE202 Study

COLLECTiVE202 is a double-blind, placebo-controlled, randomized clinical trial conducted at sites in the United States, Europe, and Australia. The study enrolled 114 patients, between the ages of 18 and 75 years, with mild-to-moderate ulcerative colitis who had not been exposed to any biologic or advanced oral therapies. Either VE202 (N=57) or placebo (N=57) was added to a patient's stable background ulcerative colitis therapy. The primary endpoints were safety and Week 8 endoscopic response (defined as a reduction of at least 1 point on the Mayo endoscopic subscore). Secondary endpoints included clinical response and remission, endoscopic improvement and remission, as well as histological assessments and measures of colonization, quality-of-life and inflammatory biomarkers. For more information on COLLECTiVE202 (NCT05370885), visit clinicaltrials.Gov.

About Vedanta Biosciences

Vedanta Biosciences is a clinical-stage biopharmaceutical company developing microbiome-based oral medicines for the treatment of gastrointestinal diseases. The company's lead asset is a potential first-in-class therapy, VE303, currently in a global Phase 3 registrational trial for prevention of recurrent C. Difficile infection. Vedanta leverages its proprietary industry-leading product engine to develop therapeutic drug candidates based on defined bacterial consortia. The product engine is supported by broad foundational intellectual property and spans the development lifecycle from discovery to commercialization. It includes one of the largest libraries of bacteria isolated from the human microbiome, vast clinical datasets, proprietary capabilities in consortium design, and end-to-end CGMP manufacturing capabilities at commercial launch scale.

View source version on businesswire.Com: https://www.Businesswire.Com/news/home/20250813508109/en/

Contacts

MediaNichole BobbynTen Bridge CommunicationsTBCVedanta@tenbridgecommunications.Com

Investors and MediaChris Brinzey+1 617-835-9304Chris.Brinzey@westwicke.Com

Adults With Periodontitis Transmit Bacteria That Can Later Cause The ...

Adults with periodontitis transmit bacteria that can cause the disease in future to their children, and the bacteria remain in the oral cavity even when the children undergo treatment of various kinds, reinforcing the need for preventive care in the first year of a baby's life.

This is the main conclusion of a study conducted at the University of Campinas (UNICAMP) in the state of São Paulo, Brazil. An article on the study is published in Scientific Reports.

Periodontitis is an inflammation of the periodontium, the tissue that supports the teeth and maintains them in the maxillary and mandibular bones. The disease is triggered by bacterial infection. Symptoms include bleeding of the gums and halitosis.

In severe cases, it leads to bone and tooth loss. If the bacteria or other microorganisms that cause the disease enter the bloodstream, they may trigger other kinds of inflammation in the body. Treatment includes cleaning of the pockets around teeth by a dentist or hygienist and administration of anti-inflammatory drugs or antibiotics.

"The parents' oral microbiome is a determinant of the subgingival microbial colonization of their children," the article's authors state in their conclusions, adding that "dysbiotic microbiota acquired by children of periodontitis patients at an early age are resilient to shift and the community structure is maintained even after controlling the hygiene status".

According to dental surgeon Mabelle de Freitas Monteiro, first author of the article, she and her group have been researching periodontitis for ten years, observing parents with the disease and its impact on their children's health.

"If the findings are applied to day-to-day dental practice, the study can be said to help design more direct approaches. Knowing that periodontal disease may affect the patient's family is an incentive to use preventive treatment, seek early diagnosis and mitigate complications," said Monteiro, who was supported by FAPESP via two projects.

The principal investigator for both projects was Renato Corrêa Viana Casarin, a professor at UNICAMP's Piracicaba Dental School (FOP) and last author of the article.

For Casarin, parents should start caring for the health of their children's gums when they are infants.

This pioneering study compares parents with and without periodontitis. In children of the former, we found subgingival bacterial colonization at a very early age. However, 'inheriting' the problem doesn't mean a child is fated to develop the disease in adulthood. Hence the importance of keeping an eye open for the smallest signs and seeking specialized help."

Renato Corrêa Viana Casarin, Study Last Author and Professor, Piracicaba Dental School, University of Campinas

Data on the Brazilian population's oral health is scarce. According to the last national dental epidemiological survey, conducted by the Ministry of Health in 2010, 18% of children aged 12 had never been to the dentist and 11.7% had experienced bleeding of the gums. In the 15-19 age group, 13.6% had never visited a dental clinic. Another survey was scheduled for 2020 but had to be postponed because of the COVID-19 pandemic.

The São Paulo State Department of Health published the findings of its latest oral health survey in 2019, showing among other things that 50.5% of adults aged 35-44 complained of toothache, bleeding gums and periodontitis

Bacteria

In the FOP-UNICAMP study led by Casarin and Monteiro, samples of subgingival biofilm and plaque were collected from 18 adults with a history of generalized aggressive (grade C) periodontitis, their children aged 6-12, and 18 orally healthy adults.

In addition to a clinical analysis, the samples were also subjected to a microbiological analysis and genetic sequencing by researchers at Ohio State University in the United States under the supervision of Professor Purnima Kumar.

"Children of periodontitis parents were preferentially colonized by Filifactor alocis, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, Fusobacterium nucleatum and several species belonging to the genus Selenomonas even in the absence of periodontitis," the article states. "These pathogens also emerged as robust discriminators of the microbial signatures of children of parents with periodontitis."

Casarin told Agência FAPESP that despite bacterial plaque control and vigorous brushing the children of people with the disease still had the bacteria in their mouths, whereas the effects of dental hygiene and prophylaxis were more significant in the children of healthy subjects.

"Because the parents had periodontitis, their children assumed this community with disease characteristics. They carried the bacterial information into their adult lives," he said, adding that the analysis of bacterial colonization pointed to a greater likelihood of transmission by the mother. The research group will now work with pregnant women in an effort to "break the cycle" by preventing bacterial colonization of their children's mouths.

"We'll treat the mothers during pregnancy, before the babies are born, and try to find out if it's possible to prevent bacterial colonization from occurring," Casarin said, noting that studies with patients will proceed only when control of the pandemic permits.

Recognition

The periodontitis research group led by Casarin has won prizes at home and abroad. In 2019, Monteiro topped the clinical research category of the IADR's Hatton Competition. The IADR (International Association for Dental Research) hosts the world's leading conference on dentistry, and the competition is designed to provide an opportunity for the best junior investigators to present their research.

Source:

Journal reference:

Monteiro, M. F., et al. (2021) Parents with periodontitis impact the subgingival colonization of their offspring. Scientific Reports. Doi.Org/10.1038/s41598-020-80372-4.

---