Tag Archives: FMT

Phase 3 Trial: Fecal Microbiota Transplantation Fails in IBS

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PH Johnsen et al. The Lancet, 2026 (published online September 24, 2026) https://doi.org/10.1016/S0140-6736(26)01424-8 Faecal microbiota transplantation in irritable bowel syndrome (REFIT2): a randomised, double-blind, placebo-controlled, phase 3 trial

Methods: This was a randomised, double-blind, multicentre study at five hospitals in Norway. Participants (median age 36 years, 65% women) were randomly assigned 2:1 to faecal microbiota transplantation (FMT) with faeces samples from either healthy donors (intervention, n=298) or the participants themselves (placebo group, n=150). All participants had baseline screening including prior colonoscopy. At baseline, the intervention group had 38% receiving a low FODMAP diet compared to 39% in the placebo group. There was also a similar degree of IBS severity: 93% and 96% had moderate-to-severe IBS, respectively. Each participant received one retention enema (60 g faeces); in the intervention group, the enema consisted of faeces from one of three donors.

Key findings:

  • 119 (40%) participants in the donor FMT group and 57 (38%) in the placebo group showed an improvement of at least 75 points on the IBS-SSS at 90 days after treatment.
  • The proportion of participants with adverse events was similar in the two study groups; however, the six serious adverse events all occurred in the donor FMT group; these included diverticulitis, cholecystitis, escalation of psychiatric condition, and appendicitis.
  • At 90 days after treatment, recipients of donor faecal microbiota transplantation showed a significant change in relative microbial abundance compared with baseline, and both relative microbial abundance and alpha diversity were significantly different in the intervention and placebo groups.
Treatment success at 90 days and 365 days follow-up. Treatment success defined as a 75-point drop in IBS-SSS score compared with baseline. IBS-SSS=Irritable Bowel Syndrome-Severity Scoring System.

Discussion points:

  • “Some earlier trials have reported clinical benefits of faecal microbiota transplantation in IBS; however, many studies have been limited by small sample sizes, single-donor designs, and less stringent endpoint definitions or did not allow for a robust assessment of donor-dependent effects… Although the gut microbiota might still contribute to IBS pathophysiology,
    these findings indicate that non-specific microbiota replacement strategies are unlikely to provide consistent therapeutic benefit.”
  • “The strengths of the current trial were the large sample size, rigorous design with double-blinding, random assignment of participants by donor, and multicentre recruitment.”
  • Limitations: “The reliance on patient-reported outcome measures is an inherent limitation in IBS trials, as few objective measures are available to assess clinical effects.”

My take (borrowed from the authors): “This phase 3 trial did not show any clinical benefit of
faecal microbiota transplantation for treating patients with moderate or severe IBS.”

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Dr. Stacy Kahn: Clostridioides difficile 2026

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Recently, Dr. Stacy Kahn gave our group an excellent update on Clostridioides difficile. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides. Dr. Kahn has been a leader on treatment and advocacy for C. difficille. In 2025, she received the Leadership Award from the Peggy Lillis Foundation recognizing her clinical, research and advocacy efforts related to C. difficile awareness and treatments.

Key points:

Diagnosis: C. diff is difficult to diagnose. The NAAT-based assays are highly sensitive but cannot readily distinguish active infection from colonization. ELISA toxin assays have higher specificity. However, there are many of these assays and their reliability in identifying active infection from colonization varies. In individuals with underlying diseases like IBD and IBS, this can create uncertainty about the diagnosis of C. diff.

Presentation: Symptoms are quite variable, from asymptomatic to bloody diarrhea to fulminant colitis (uncommon in kids). Profound urgency is a common feature.

Transmission: C. diff bacteria can survive on surfaces for 24 hrs. The spores can survive months to years. In addition, the (invisible) spores are highly resistant to heat, disinfection and antimicrobials. Thus, nursing homes and hospitals are frequent reservoirs.

Epidemiology: C diff rates in the hospital setting have improved, likely due to antibiotic stewardship. Community rates have increased; though, precise estimates are problematic as the diagnostic testing is not straightforward.

Costs: In 2016, the estimated annual costs due to C diff were $ 6.3 billion (Zhang S. et al. BMC Infect Dis. 2016).

Resources/Websites:

Severe C diff in Children: In a retrospective study of C diff in hospitalized children (2013-2019, n=17,142 children) showed that among 23,053 CDI admissions, 74 (0.3%) had a colectomy (55 in IBD patients), and 29 (0.1%) had toxic megacolon. All-cause mortality was noted in 429 (1.9%) (Reference: Edwards PT, Kahn SA, Nicholson, M et al. J Pediatr. 2023; 252:111-116.e1. Open Access! Clostridioides difficile Infection in Hospitalized Pediatric Patients: Comparisons of Epidemiology, Testing, and Treatment from 2013 to 2019).

Testing: Recommendations include avoiding testing in those taking laxatives; however, an exception to this would be patients with motility disorders. Even combination testing cannot always distinguish between colonization and active infection. In addition, there are numerous toxin tests with variable performance.

[From prior blog post: In a large adult study with 293 of 1416 hospitalized adults testing positive for C. diff, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. (Overdiagnosis of Clostridium difficile with PCR Assays)]

Treatment:

  • 1st line treatment remains vancomycin.
  • 10-day treatment course is recommended.
  • Fidaxomicin, particularly for recurrrent C. diff could be helpful and easier to administer (2/day).
  • Prophylactic treatment (low dose vancomycin) may be appropriate in high risk individuals needing to take antibiotics.
  • FMT is no longer readily available from stool banks. Donor-directed FMT may be an option after appropriate screening. Given the lack of stool banks, urgent treatment with FMT for severe cases is not available.
  • Probiotics have not been proven effective in reducing recurrence and increase the costs for families. A diet high in fruits and veggies (‘eat the rainbow‘) could help restore a more healthy microbiome.
  • Newer treatments in adults, Vowst and Rebyota, are expensive and not readily available for children. Anecdotal reports suggest they may be beneficial in pediatric patients.

Conclusions: C diff research is difficult in pediatrics. Many of the patients who need treatment would be excluded from trials. There are very few treatment options in kids.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Rapid Gut Microbiome Recovery: Diet Outperforms Microbial Transplant

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Briefly noted: MS Kennedy et al. Nature (2025). https://doi.org/10.1038/s41586-025-08937-9. Diet outperforms microbial transplant to drive microbiome recovery in mice

Methods:  Here we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or Western Diet (WD).

Key findings: “Only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither.”

Conclusion (from authors): “Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.”

My take: This study suggests that the best way to get a “healthy” microbiome is to eat a healthy diet rather than to try to alter with FMT. This finding likely would be the same for probiotics as well.

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Fecal Microbiota Transplantation for Severe Constipation in Children

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Methods: The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) was studied in a randomized, double-blind, controlled trial with 110 children. The initial cohort recruited was 576 patients; however, 466 were excluded for not meeting inclusion criteria. All participants received a daily RCE, followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. 

Key findings:

  • At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 spontaneous bowel movements per week

There was a low response to RCE alone which the authors attributed in part to the severity of constipation in the cohort. It is unclear the degree of compliance with the treatment protocol which was done in the home setting. There was a prior open-label study with NJ FMT which improved constipation in half of participants.

My take: Modulating the microbiome can have beneficial effects on stool frequency. This can be through diet and possibly FMT in severe cases of constipation. The availability of capsules could make this type of therapy easier but perhaps less palatable. Even if FMT proves to be a useful treatment, the optimal treatment regimen is not clear.

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OpenBiome Suspending FMT Shipments

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Link: OpenBiome Voluntarily Suspends FMT Shipments

An excerpt:

On September 29, 2024, OpenBiome will voluntarily suspend the distribution of investigational Fecal Microbiota Transplants (FMT) for patients with recurrent Clostridioides difficile infection (C. diff)...

Recent interaction with the FDA has informed our decision to voluntarily suspend the distribution of all investigational FMT as we continue to seek clear direction on aligning our operations with the final Enforcement Policy published in 2022. Our commitment has always been to adhere to FDA regulations and guidelines for the manufacture and distribution of investigational FMT as a therapeutic option for patients with C. diff. Thus, this is not a safety or quality matter. Investigational FMT preparations provided by OpenBiome are manufactured and distributed in compliance with current good manufacturing practices (cGMP).    

We continue to hear from clinicians, our frontline partners, that despite the availability of FDA-approved therapeutics, there remain patients who do not respond to these treatments and, according to clinical guidelines, should have access to traditional FMT. ..

  1. Contact us. If you have a patient suffering from severe or fulminant C. diff, please contact us at 617-575-2201 or info@openbiome.org to discuss options.
  2. Share your thoughts. We believe the FDA would benefit greatly from hearing directly from survivors and their advocates about the urgent need for continued access to rigorously screened and tested FMT. If you or your C. diff patients are willing, please submit comments to ocod@fda.hhs.gov with a copy to Dr. David Kaslow, director Office of Vaccines Research and Review, at david.kaslow@fda.hhs.gov, and Dr. Peter Marks, director of the Center for Biologics Research and Evaluation at peter.marks@fda.hhs.gov. Or you may share your experiences with us directly using this FORM.  

My take: As FDA-approved therapeutics have not received a pediatric indication, NASPGHAN involvement to try to keep FMT available for children would be a worthwhile endeavor. In the absence of having FMT available from OpenBiome, NASPGHAN experts could provide guidance on best practices for refractory C diff.

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Data on Fecal Microbiota Transplantation for Ulcerative Colitis and Case Report of Vancomycin for Refractory Ulcerative Colitis

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NEH Chehade et al. Inflamm Bowel Dis 2023; 29: 808-817. Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials

HS Almomen, B Al-Bawardy. Inflamm Bowel Dis 2023; 29: 837-838. Oral Vancomycin Induced and Maintained Clinical and Endoscopic Remission in Ulcerative Colitis and Primary Sclerosing Cholangitis Post-liver Transplantation

In the first study by Chehade et al, the authors analyzed six RCTs involving 324 patients. Key findings:

  • Compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001)
  • clinical remission with FMT was 46.2% compared 22.5% for placebo
  • clinical response with FMT was 51.6% compared to 30.1% for placebo
  • endoscopic remission with FMT was 18.9% compared to 6.1% for placebo
  • endoscopic response with FMT was 36.7% compared to 22.4% for placebo

Discussion Points:

  • “The studies included in our article indicate that there is a shift in the microbiota composition of responders in the FMT group to resemble the profile of healthy donors”
  • FMT delivery via upper GI tract was equally effective as delivery via lower GI tract in these studies in inducing combined remission
  • “The understanding of FMT effectiveness for IBD is in its infancy.”

In the case report by Alomomen et al, a 34 year old with refractory ulcerative colitis and PSC (post-transplant) had not responded to infliximab, vedolizumab, adalimumab, tofacitinib or 10 months of ustekinumab (every 4 weeks). In addition, he was receiving tacrolimus therapy due to his liver transplant. His colonoscopy demonstrated a continuous Mayo 3 colitis. Subsequently, vancomycin therapy was added to his treatment (500 mg BID); he continued ustekimumab. Six months afterwards, his fecal calprotectin had dropped to 277 from 1600 and his CRP and hemoglobin had normalized. Repeat colonoscopy demonstrated complete endoscopic healing.

My take: There are many patients who do not respond to current IBD therapies. These two studies show that both FMT and vancomycin could be useful in selected patients.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

How Effective and Safe is Fecal Microbiota Transplantation in Immunocompromised Pediatric Patients with Clostridioides difficile?

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KR Conover et al. JPGN 2023; 76: 440-446. Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Pediatric Patients

In this multicenter retrospective cohort (n=42), the authors examined the efficacy and safety of fecal microbiota transplantation (FMT) in immunocompromised (IC) children with Clostridioides difficile infection (CDI).  Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%)

Key findings:

  • 23 (55%) of FMT was delivered via colonoscopy, 17 (40%) were delivered via enteric tube, and 2 (5%) via capsule
  • Success rate was 79% after first FMT and 86% after 1 or more FMT.
  • There were serious adverse events (SAEs) in 13 out of 42 (31%) patients; 4 (9.5%) of which were likely treatment-related (all patients recovered). These events included cecal perforation, aspiration pneumonitis, diarrhea and fever. Given retrospective design of study, AEs were likely underreported

My take: Though there are the potential for significant adverse effects, FMT is effective in a high percentage of immunocompromised children with CDI.

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Is Fecal Transplantation Needed To Treat Irritable Bowel? Three Year Data

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M El-Salhy et al. Gastroenterol 2022; 163: 982-994. Open Access! Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation

Background: “Fecal microbiota transplantation (FMT) might be a promising treatment for IBS, and this has been investigated in 7 randomized controlled trials (RCTs). 2 In 4 of these, FMT reduced symptoms and improved the quality of life of patients with IBS, whereas no effects were indicated in the other 3. 2 The difference in these results was likely because of differences in the protocols used, the selected donors, the cohort of treated patients, the fecal transplant dose, and the route by which the transplant was administrated.2“

Methods: In this placebo-controlled trial with 125 patients, fecal microbiota transplantation (FMT) was administered into duodenum (30 g or 60 g). The donor was a healthy male aged 36 years with a normal body mass index who was born via vaginal delivery, breastfed, a nonsmoker, was not taking any medication, was only treated a few times with antibiotics, exercised regularly, and consumed a sport-specific diet that was richer in protein, fiber, minerals, and vitamins than the average diet.

Key findings:

  • Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. 
  • Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups.
  • No long-term adverse events were recorded. The authors note in the discussion rare serious safety issues with FMT but indicate in this population without systemic diseases or immune deficiency, that adverse effects were mild and self-limited gastrointestinal symptoms

The associated editorial (815–817, Treatment of Irritable Bowel Syndrome Using Fecal Microbiota Transplantation: A Step Forward?) noted that 25% of patients in the donor FMT continue to experience severe symptoms based on IBS-SSS>300; in addition, 50% (in 30 g) and 40% (in 60 g) had moderately severe IBS scores >175.

The editorial suggests that overall response is modest bust similar to FDA-approved medications for IBS. The number needed to treat (NNT) would be 4-5 patients to reduce the proportion with severe IBS-SSS based on per-protocol analysis (most IBS medications range from 6 to 10).

My take: This study strengthens the notion that alterations in our microbiome can the outcomes of patients suffering from IBS. Now, we have to identify which patients will benefit from this approach and how to optimally modify the microbiome. In addition, this study suggests that finding an optimal FMT donor will impact results given variability in prior trials.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Why Stool Hoarding Might Be A Good Idea

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SK Hourigan et al. JPGN 2021; 73: 430-432. Updates and Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children

This good update provides a lot of useful information regarding fecal microbiota transplantation (FMT) and a word of caution regarding its future availability.

Key points regarding FMT:

  • Long-term safety remains unknown. FMT may lead to susceptibility to chronic inflammatory, allergic, and autoimmune diseases. “FMT has been associated with durable transmission of pro-carcinogenic bacteria from adult donors to pediatric recipients…although the long-term consequences…are unknown.”
  • Due to transfer of extended spectrum beta-lactamase (ESBL) E coli to 2 immunocompromised adult recipients, further screening of FMT was implemented.
  • Though there is no published evidence of SARS-CoV-2 fecal transmission, the FDA “advised additional precautions and testing in March 2020; “however, there are no molecular tests with stool…which have received emergency use authorization.” Hence, most FMT programs were on hold as of January 2021.
  • After 2021, OpenBiome, whose product was recently available again, is expected to stop distribution of FMT donor product due to increased costs of screening and the “promising biotherapeutics” that are in phase III trials.
  • Biotherapeutic is “loosely defined as drug therapy products where the active substance is extracted from a biological specimen.” The new products are likely to have “increased standardization, safety and practicality.”
  • The problem in pediatrics: none of these biotherapeutic products have started trials in children. This will lead to treatment problems. Even if one wanted to set up donor-directed FMT, it will be difficult to complete all of the screening recommended by the FDA. It could lead to self-administration by families with uncertain risks.

My take: My first reaction to this article: ‘Oh crap!’ It is sad and ironic that I will miss having available commercial stool for FMT.

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Long-term Safety of Fecal Microbiota Transplantations

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S Saha et al. Gastroenterol 2021; 160: 1961-1969. Full text PDF: Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection

In this prospective study (2012-2018) with 609 patients (median age 56 years), the authors studied long-term outcomes. Key findings:

  • At 1 year, 9.5% reported additional CDI episodes. Diarrhea occured in more than half of all patients, although it lasted for than a week in most patients.
  • Among 477 with long-term data, 188 patients post-FMT developed new medical conditions/symptoms.
  • Weight gain was reported by 46 patients (10.3%) post-FMT. In these patients, the median weight gained was 30 pounds (range, 10–70). Of these patients, 11 (23%) had
    preexisting obesity.
  • Approximately 3% of patients each reported new-onset diabetes mellitus and dyslipidemia,
    whereas 2.3% reported thyroid disease.
  • Gastrointestinal symptoms were the second most frequently reported (13.4%). New-onset IBS was reported by 4%, IBD by 0.3%, chronic diarrhea by 5.0%, and chronic constipation by 1.6% of patients.
  • Serious infections were reported by 11.8% of patients: CDI in 5.7%, Pneumonia in 4.5%, UTI in 1.8% and Sepsis in 1.2%. Median time to the infections was 29 months (range, 0–73) following FMT; only 1 patient reported an infection (CDI) within the first month after FMT.
  • No deaths were considered related to FMT
  • Limitation: no control group

My take (borrowed from authors): “FMT appears safe and effective, both in the
short-term and long-term. Several new medical conditions were reported post-FMT, in particular, weight gain and IBS.”

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