Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active Crohnʼs Disease

Abstract

Objective Crohn’s disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal Microbial Transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. Design Nine patients, ages 12–19 years, with mild to moderate symptoms defined by Pediatric Crohn’s disease activity index (PCDAI of 10–29) were enrolled into a prospective open label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein (CRP), and fecal calprotectin were evaluated at each study visit. Results All reported adverse events (AE) were graded as mild except for one individual who reported moderate abdominal pain after FMT. All AE were self limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in seven out of nine patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6, and at 6 weeks to 8.6 ± 4.9. Based upon PCDAI, 7/9 patients were in remission at 2 weeks, and 5/9 patients who did not receive additional medical therapy were in remission at week 6 and 12 weeks. No or modest improvement were seen in the patients who did not engraft or whose microbiome was most similar to their donor. Conclusion This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for Crohn’s disease. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with Crohn’s disease.

Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease

“…127 Another study in pediatric patients reported only mild adverse events with one case of moderate abdominal pain, all of which were self-limiting. 120 These findings suggest that FMT for IBD is a safe procedure although the numbers in each trial are small. Given the decreased efficacy of FMT for C. difficile infection in patients with underlying IBD, 130 it is possible that the increased side-effects noted in this population are confounded by the presence of both diseases.…”

“…FMT may also be a potential treatment of pediatric CD, as one recent case series noted remission in 5 of 9 patients (56%) after FMT, with 7 of 9 patients (78%) demonstrating engraftment of donor microbiota. 120 Interestingly, although one study did not find a significant decrease in Crohn's disease severity following FMT, patients reported significantly increased quality of life scores after the procedure. 108 Prior work from one of us for FMT in active Crohn's disease (defined as HBI 5) had mixed results.…”

“…A common theme among published studies is that those who achieve normalization of the gut microbiota, or are more similar to their donor, typically experience improved clinical outcomes. 107,109,112,120,121 A key issue moving forward, therefore, will be to understand how donor microbiota engraftment can be improved, as this alone may lead to increased success with FMT. Perhaps one reason why some studies have had more encouraging results is due to multiple FMTs, which suggests those studies may have achieved a higher rate of engraftment.…”

Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation

“…15 Thus, targeting intestinal microbiota to regulate the visceral pain seems to be an interesting therapeutic approach. Indeed, fecal transplants might be a highly effective treatment of chronic diseases 16,17 and reduce symptoms in IBS patients. 18 Dietary intervention by probiotics can also be used in the manipulation of intestinal microbiota.…”

Fecal microbiota transplantation in gastrointestinal diseases. What practicing physicians should know

“…34, [39][40][41][42][43] There are multiple trials currently underway to examine the potential benefits of FMT in such conditions and these are listed on ClinicalTrials. gov at the time of writing (tAbLe 2).…”