Stool Donor Research Articles

Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation.

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients’ gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.5 yr post-FMT compared with the stool donor. Feces were subjected to DNA sequencing to characterize bacteria and double-stranded DNA (dsDNA) viruses including phages. The patient's microbial communities varied over time and showed little overall similarity to the donor until 7 mo post-FMT, indicating ongoing gut microbiota adaption in this time period. After 4.5 yr, the patient's bacteria attained donor-like compositions at phylum, class, and order levels with similar bacterial diversity. Differences in the bacterial communities between donor and patient after 4.5 yr were seen at lower taxonomic levels. C. difficile remained undetectable throughout the entire timespan. This demonstrated sustainable donor feces engraftment and verified long-term therapeutic success of FMT on the molecular level. Full engraftment apparently required longer than previously acknowledged, suggesting the implementation of year-long patient follow-up periods into clinical practice. The identified dsDNA viruses were mainly Caudovirales phages. Unexpectedly, sequences related to giant algae–infecting Chlorella viruses were also detected. Our findings indicate that intestinal viruses may be implicated in the establishment of gut microbiota. Therefore, virome analyses should be included in gut microbiota studies to determine the roles of phages and other viruses—such as Chlorella viruses—in human health and disease, particularly during RCDI.

Fecal Transplant in Refractory Clostridium difficile Colitis

Clostridium difficile infections are becoming more common, more severe, and more likely to recur. Conventional treatment with antibiotics often fails to eradicate the infection; even when it succeeds, recurrent infection is common. Complementary treatment with probiotic agents to reconstitute the physiological intestinal flora does not yield any consistent benefit. In recent years, fecal transplantation has been used in the English-speaking countries with cure rates of about 87%, but the available evidence is limited to large case series. No randomized controlled trials have been performed. We present the case of a 73-year-old woman with intractable, recurrent enterocolitis due to Clostridium difficile who was successfully treated with fecal transplantation via colonoscopy. Upon the completion of antibiotic treatment for a second recurrence of enterocolitis, stool in liquid suspension was introduced into the patient's colon through a colonoscope. Prior testing had shown the stool donor to be free of acute infection or stool pathogens. The patient was given loperamide to prolong contact of the stool transplant with the colonic mucosa. She was also treated with Saccharomyces cerevisiae for four weeks. There was no clinical or microbiological evidence of a further recurrence of enterocolitis for 6 months after transplantation. Stool transplantation had no adverse effects. This patient had a lasting remission of enterocolitis due to Clostridium difficile after the treatment described above. Fecal transplantation seems to be a safe and highly effective treatment for recurrent Clostridium difficile infection. It is unclear whether the administration of Saccharomyces cerevisiae confers any additional benefit.

Fecal Bacteriotherapy in a 6 Year Old Patient With Ulcerative Colitis and Clostridium Difficile

Inflammatory bowel disease (IBD) is thought to be a disorder of the innate and reactive immune system, and its interaction with the gastrointestinal microbiome. A growing body of literature supports the use of fecal bacteriotherapy in eradicating Clostridium difficile (C. diff) infections. Its use in IBD has been reported but not established. 20-25% of IBD patients present in childhood. Current available IBD therapies pose significant challenges, especially in young children with IBD, due to their side effects and route of administration. We discuss our experience with fecal bacteriotherapy in a 6 year old child with relapsing Ulcerative Colitis (UC) and recurrent C. diff infection. A 6 year old female was diagnosed with UC after presenting with bloody stools, abdominal pain, anemia and elevated ESR. Initial colonoscopy showed pancolitis and a normal terminal ileum. Due to lack of response to oral mesalamine and steroid dependence, azathioprine was started with rectal mesalamine and rectal steroids. Allopurinol was added after breakthrough symptoms and severe anemia. She continued to have intermittent moderate symptoms (blood, diarrhea) at 1 year out from diagnosis. C. diff antigen and toxin were present, and persisted despite treatment with metronidazole and vancomycin. The family was interested in pursuing fecal bacteriotherapy prior to initiating further antibiotic courses and infliximab. Approval was obtained from bioethics committee. Her mother was the stool donor and was screened for stool infections, viral hepatitis and HIV. At baseline, a sigmoidoscopy showed no pseudomembranes, but microscopic moderate chronic active colitis. A nasogastric (NG) tube was placed. Fresh donor stool was mixed with saline then superfiltrated to 30 cc suspension. The suspension was instilled via NG tube uneventfully post procedure, after which it was removed and the patient discharged home. Symptoms and stool inflammatory markers were followed from baseline to 16 weeks post procedure. No treatments aside from azathioprine and allopurinol were used. Stool calprotectin decreased from 504 at baseline to 76 by week 12. C.diff antigen and toxin were cleared by 3 weeks. Microbiome analysis of the donor stool and the patient's stool before and at 3 periods after bacteriotherapy are pending and will be finalized shortly. We describe a case of successful fecal bacteriotherapy for a child with recalcitrant UC and C diff. The implication of the improved calprotectin will be further explored with reducing her current medications. The relative ease, tolerability and success of the procedure should encourage further study.

Systematic Review of Intestinal Microbiota Transplantation (Fecal Bacteriotherapy) for Recurrent Clostridium difficile Infection

Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.

Nature’s Therapy for RecurrentClostridium DifficileDiarrhea

Nature’s Therapy for Recurrent<i>Clostridium Difficile</i>Diarrhea