Fecal Microbiota Transfer in Patients With Chronic Antibiotic-Refractory Pouchitis

Stallmach, Andreas; Lange, K.; Buening, J.; Sina, Christian; Vital, Marius; Pieper, Dietmar H.

doi:10.1038/ajg.2015.436

Cited by 73 publications

(90 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reason for the low engraftment in our study could be due to several factors, including donor selection, the dose and frequency of FMT, and the pouch microenvironment. The low donor engraftment found in our study may also explain the inconsistent and partially contradictory results of the other small controlled and uncontrolled observations of FMT in patients with chronic refractory pouchitis or ADP [8, 17]. Further studies need to determine the mechanisms of engraftment in the small bowel environment.…”

Section: Discussionmentioning

confidence: 48%

“…We based our power calculations on the previous observations by Stallmach et al [8] in 5 patients with refractory ADP reporting a response rate of 100% and a remission rate of 80%. Since our targeted patient group was antibiotic dependent but not antibiotic refractory, we conservatively estimated a remission rate of 80% and assumed a placebo response of 10%.…”

Section: Discussionmentioning

confidence: 99%

“…We assumed a placebo remission rate (defined as clinical remission and no need for antibiotics) of 10%. A recent case series by Stallmach et al [8] suggested an antibiotic-free remission rate of 80% and a response rate of 100% in the setting of repeated FMT. With 20 patients (1: 1 randomization), and a placebo response rate of 10%, we had an 80% power to detect an effect difference of 67.5%, that is, an antibiotic-free remission rate of 77.5% in the treatment group (2-sided, alpha = 0.05, Fisher-Irwin’s exact conditional test).…”

Section: Methodsmentioning

confidence: 99%

“…Microbial dysbiosis, which can only be controlled with antibiotics, is thought to be a major driver of clinical symptoms in patients with ADP [7]. A preliminary pilot study recently reported a sustained response for at least 3 months in 3 out of 5 ADP patients after FMT [8]. However, at least 3 endoscopically applied FMTs (eFMTs) were necessary to achieve a response.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment

et al. 2019

View full text Add to dashboard Cite

Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP. Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene. Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response. Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.

show abstract

Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Oral administration is very common using capsules containing the gut microbiota of healthy donors after pathogen-free screening, stool purification and preservation processes (107). In addition, FMT has also been effective in treating diseases like ulcerative colitis (108) and chronic pouchitis (109) in clinical practice. Although FMT has not been used in T1D treatment, if specific combinations of beneficial bacteria could be identified, this could be a promising therapy, given that fecal filtrate has a similar efficacy to fecal microbiota in treating other medical conditions (110).…”

Section: Fecal Microbiota Transfer (Fmt) As a Potential Therapymentioning

confidence: 99%

Antibiotics, gut microbiota, environment in early life and type 1 diabetes

Wong

2017

Pharmacological Research

View full text Add to dashboard Cite

The gut microbiota interact with innate immune cells and play an important role in shaping the immune system. Many factors may influence the composition of the microbiota such as mode of birth, diet, infections and medication including antibiotics. In diseases with a multifactorial etiology, like type 1 diabetes, manipulation and alterations of the microbiota in animal models has been shown to influence the incidence and onset of disease. The microbiota are an important part of the internal environment and understanding how these bacteria interact with the innate immune cells to generate immune tolerance may open up opportunities for development of new therapeutic strategies. In this review, we discuss recent findings in relation to the microbiota, particularly in the context of type 1 diabetes.

show abstract