III. 3. The FMT Procedure

Knowing what to expect is part of the treatment: this chapter walks through each delivery method and what sensations count as normal.

Knowing What to Expect Is Part of the Treatment

The FMT procedure is not a single, uniform event. Depending on the delivery route, the patient's diagnosis, and the phase of treatment, the experience will differ significantly. What is consistent across all formats is that the procedure is designed to be safe, minimally invasive, and reproducible. Understanding what will happen – and what sensations and responses are normal – reduces anticipatory anxiety and substantially improves adherence to the full treatment course [44].

This chapter describes the procedural experience from the patient's perspective for each delivery format used in FMT practice: colonoscopic delivery, capsule-based oral FMT, and retention enema. The focus is on what the patient will experience directly – before, during, and immediately after each procedure type – alongside the clinical rationale for each step. Specific warning signs that require immediate medical contact are addressed in detail in Chapter II.4.

Colonoscopic FMT – The High-Dose Induction Procedure

Colonoscopic FMT is the highest-dose delivery method currently in clinical use. It is typically reserved for Phase 1 induction in recurrent Clostridioides difficile infection and in selected non-CDI patients requiring rapid and deep microbial community seeding. The procedure follows the same general framework as a diagnostic colonoscopy and is performed by a gastroenterologist or colorectal specialist in an endoscopy unit.

Before the procedure. The patient will have completed bowel preparation as described in Chapter II.2. On arrival at the endoscopy unit, a brief clinical assessment is performed: vital signs are recorded, any changes in symptoms or medications since the last clinical contact are noted, and written informed consent is confirmed. An intravenous cannula is typically placed for sedation access. The patient changes into a procedure gown and is positioned in left lateral decubitus on the procedure table. Light to moderate conscious sedation – most commonly with midazolam and fentanyl, or propofol depending on local practice and patient preference – is administered by an anaesthetist or trained endoscopy nurse [29]. The patient remains conscious and responsive but is typically relaxed and experiences little or no discomfort during the procedure itself.

During the procedure. The colonoscope is advanced through the entire colon to the caecum and terminal ileum under direct visualization. The total insertion time is typically 10–20 minutes. Once the colonoscope is positioned at the caecum, the FMT preparation – a processed and filtered donor stool suspension in normal saline or glycerol, with a total volume of 150–300 mL – is infused through the working channel of the colonoscope as the instrument is slowly withdrawn [29], [35]. The infusion is distributed across the right colon, transverse colon, and left colon during withdrawal, maximizing mucosal surface contact and reducing the risk of the preparation pooling in a single segment. The patient typically feels mild cramping or a sense of fullness during infusion, which resolves quickly. Total procedure time from scope insertion to withdrawal is usually 20–40 minutes.

After the procedure. The patient is moved to a recovery area and monitored for 30–60 minutes as the sedation wears off. Vital signs are checked at regular intervals. Mild abdominal discomfort, bloating, or urgency to defecate is common in the first 1–2 hours and is expected: the introduced preparation volume and the mechanical stimulation of the colonoscopy both contribute to increased intestinal activity. Patients are encouraged to retain the preparation for as long as possible after the procedure – ideally at least 30–60 minutes before defecation – to maximize mucosal contact time [35]. A responsible adult must accompany the patient home if sedation was used; driving is not permitted on the day of the procedure. Patients may resume a light normal diet the same afternoon or evening. Most patients report returning to their usual level of function within 24 hours [44], [29].

Capsule-Based Oral FMT – The Repeated-Dose Protocol

Oral capsule FMT is the primary delivery format for the compatibility assessment phase (Phase 0), the consolidation phase (Phase 2), and the step-down phase (Phase 3) of the MicroBiome Bank protocol. It is also used for intensive induction in selected patients where colonoscopy is contraindicated or not preferred. Capsules contain lyophilized or frozen-processed donor microbiota encased in acid-resistant outer shells designed to survive gastric transit and release their contents in the small intestine and colon [45], [46].

Before taking capsules. No fasting or bowel preparation is required. The patient should have eaten a regular meal 30–60 minutes before taking the capsules – a fed stomach facilitates gastric emptying, speeds intestinal transit, and provides the fermentable substrate the incoming microbiota needs upon release [46]. Water intake of at least 200–300 mL should accompany capsule ingestion to support capsule transit and hydration of the lyophilized preparation. Patients should avoid taking the capsules immediately before lying down, as recumbent posture slows gastric emptying and may delay small intestinal delivery.

Taking the capsules. The prescribed number of capsules – which varies by phase and individual protocol – should be taken in one sitting with the prescribed quantity of water. Capsules should not be opened, chewed, or dissolved before swallowing: the acid-resistant coating is integral to the delivery mechanism and its disruption would expose the microbial content to gastric acid, dramatically reducing viability [45]. If swallowing multiple capsules is difficult, the patient may take them in two or three smaller groups over 10–15 minutes; each group should be accompanied by a full glass of water. Some patients experience mild nausea when taking larger capsule doses; this is transient and usually resolves within 30–60 minutes. If nausea is severe or accompanied by vomiting, the clinical team should be notified, as vomited capsules cannot be replaced without clinical assessment.

After taking capsules. Normal activities may be resumed immediately. No rest period is required. In Phase 0, patients should begin or continue their Food and Symptom Diary entries from the same day: stool changes, abdominal symptoms, energy level, and any unusual sensations should be recorded daily. Changes in stool frequency, colour, or consistency in the 24–72 hours following capsule intake are common and typically reflect the initial ecological response to the donor preparation rather than pathological processes. Stool may appear looser, darker, or more frequent than baseline during this period; this is a normal and expected finding, not a warning sign, provided no blood is present and the patient is not systemically unwell [46], [47].

Retention Enema FMT – Lower Bowel Delivery

Retention enema delivery of FMT is used in specific clinical contexts: as a maintenance format in selected ulcerative colitis patients, in patients for whom colonoscopy is not feasible and capsule tolerance is poor, and occasionally for distal colonic disease where targeted lower bowel delivery is preferred. The enema preparation volume is typically 60–150 mL of processed donor suspension, administered via a standard enema catheter inserted rectally [29], [35].

The procedure. The patient lies in left lateral decubitus position with knees drawn up. A lubricated catheter is gently inserted approximately 10–15 cm into the rectum. The suspension is slowly instilled by gravity or gentle manual pressure over 2–5 minutes. The catheter is removed and the patient is asked to retain the preparation for a minimum of 30 minutes, ideally 1–2 hours. Longer retention times are associated with higher proportional colonic distribution of the preparation and improved clinical outcomes [35]. To assist retention, the patient may change position during the retention period – moving from left lateral to supine to right lateral at 10–15 minute intervals has been shown to improve distribution through the left colon and splenic flexure. Mild urgency to defecate is expected and can usually be suppressed with relaxation and positional adjustment; if urgent defecation occurs before 20–30 minutes, the clinical team should be notified.

Efficacy evidence (2024). Allegretti et al. (2024) network meta-analysis of 47 RCTs (n=3,892) concluded: colonoscopic FMT remains most efficacious for rCDI (89% cure), but capsule-based FMT and rectally administered LBP (Rebyota) achieve equivalent outcomes for first-recurrence prevention [411]. This supports patient-tailored decision-making — based on patient preference as well as clinical factors — when selecting the delivery route.

Procedural Comparison – What the Patient Experiences

Table 5 – Comparison of FMT delivery routes from the patient perspective # Sensations described are typical; individual experience varies. Any sensation outside the expected range described above should be reported to the clinical team.

What Is in the FMT Preparation – Processing, Safety, and Storage

The donor material used in MicroBiome Bank FMT preparations undergoes a structured multi-step processing protocol before administration. Understanding this process addresses a concern common among patients and supports informed consent.

Donor screening. All MicroBiome Bank donors are healthy adults who have undergone extensive screening including blood tests (HIV, hepatitis B and C, HTLV, syphilis, CMV, EBV), stool cultures (C. difficile, enteric pathogens, ova and parasites, Helicobacter pylori, norovirus, rotavirus, adenovirus), extended pathogen PCR panels, and a detailed health and lifestyle questionnaire. Screening is repeated every 3 months during active donation. This protocol meets or exceeds the standards established in the European Consensus Conference on FMT [36] and the OpenBiome/international stool bank guidelines [48]. Since 2020, SARS-CoV-2 screening has been added to the standard protocol [49].

Processing and formulation. Donated material is processed within a defined time window after collection, typically under anaerobic or reduced-oxygen conditions to maximize viability of obligate anaerobic bacteria – the taxa most critical for SCFA production and colonization resistance. The preparation is filtered to remove particulate matter, standardized for microbial density, and mixed with a cryoprotective medium before lyophilization (freeze-drying) or freezing. Lyophilized preparations retain viability for months to years under appropriate storage conditions and allow room-temperature shipping, which is essential for outpatient capsule protocols [45], [46]. Frozen preparations are stored at −80°C and thawed immediately before use in colonoscopic or enema procedures.

Safety record. The serious adverse event rate in FMT – defined as events requiring hospitalization, specific medical treatment, or resulting in permanent harm – is low in appropriately screened patients. A 2021 systematic review of 4,241 FMT procedures reported a serious adverse event rate of approximately 1–2%, with the majority attributable to the endoscopic procedure rather than the FMT material itself [50]. Transmission of pathogens not covered by standard screening protocols has occurred in rare instances in the published literature, highlighting the ongoing importance of rigorous and updated donor screening as new pathogen risks emerge. Patients with severe immunosuppression (e.g., post-bone marrow transplant, high-dose corticosteroid use) carry higher procedural risk and receive individualized risk-benefit assessment before FMT is initiated [49].

Microbiota Effects

• Colonoscopic FMT achieves the highest per-procedure microbial density delivered to the colon, with direct mucosal contact across the entire colonic surface; these properties are associated with the most rapid and complete initial community shifts observed in clinical studies, typically detectable within 24–72 hours of the procedure [29], [35].
• Capsule-based oral FMT delivers viable microbial communities to the ileum and proximal colon; acid-resistant capsule coatings are effective at protecting a significant proportion of the microbial content from gastric acid inactivation, though viability losses of 20–60% during gastric transit have been reported depending on capsule formulation and gastric pH at the time of ingestion [45], [46].
• Retention time after enema FMT directly predicts clinical outcomes in distal colonic disease: each additional 30 minutes of retention increases estimated mucosal contact time with the preparation, improving the probability of microbial attachment and initial colonization [35].
• Sedation used during colonoscopic FMT does not appear to meaningfully affect engraftment rates; however, opioid-based sedation agents transiently slow intestinal motility, which may extend colonic retention of the infused preparation and potentially benefit post-procedural distribution [29].
• Anaerobic processing of FMT preparations substantially improves the viability of obligate anaerobes – including butyrate-producing taxa such as Faecalibacterium prausnitzii^[G], Roseburia intestinalis, and Eubacterium rectale – compared to preparations processed under ambient oxygen conditions; preparations manufactured under anaerobic conditions show higher post-transplant SCFA production in recipient stool in controlled studies [47].
• Lyophilization (freeze-drying) preserves microbial community composition and viability over extended storage periods, though modest shifts in community composition relative to the fresh original material have been reported; the clinical significance of these shifts for engraftment outcomes is currently being evaluated in comparative trials [45].
• The donor microbiome's ecological profile – including its diversity, keystone species composition, and bacteriophage community – is transferred to the recipient during the procedure and constitutes the primary determinant of post-FMT community structure; the procedural route modulates the density and spatial distribution of this transfer but does not fundamentally alter which species are introduced [8].

Patient Guidance

• Before any FMT procedure, confirm with your clinical team exactly what format you will receive (colonoscopy, capsule, or enema), the planned date and time, and any preparation steps that still need to be completed. Do not assume preparation requirements are the same as for a previous procedure.
• If you are scheduled for colonoscopic FMT: arrange for a responsible adult to accompany you and to drive or escort you home. You will not be permitted to drive on the day of the procedure due to sedation. Plan to be at the endoscopy unit for 2–3 hours in total, including preparation, procedure, and recovery time.
• If you experience significant anxiety about the colonoscopic procedure, discuss this with your clinical team in advance. Anxiolytics or modified sedation protocols can be arranged if needed; unmanaged anticipatory anxiety reduces cooperation during the procedure and increases the perceived discomfort.
• For capsule FMT: take your capsules with a full glass of water (200–300 mL minimum), after a regular meal, and do not lie down immediately after ingestion. If you feel nauseous, remain upright and breathe slowly; the sensation typically passes within 30–60 minutes. Do not open or crush the capsules under any circumstances.
• For retention enema FMT: prepare your environment before the procedure – have towels, a comfortable position, and if possible a clock visible to time your retention period. Start in left lateral position, then slowly rotate to supine and right lateral at 15-minute intervals if you can tolerate it. Each additional minute of retention above 30 minutes increases the effectiveness of the procedure.
• In the 24–72 hours after any FMT procedure, expect changes in your stool: looser consistency, darker colour, increased frequency, or increased flatulence are all normal and expected responses reflecting the initial ecological activity of the donor community. These changes do not require treatment and should not alarm you.
• Record your symptoms in your Food and Symptom Diary starting on the day of the procedure. Note the time you received the preparation, your first post-procedure stool (time, Bristol scale score), any abdominal sensations, your energy level, and what you ate. This record is your clinical team's primary monitoring tool in the days immediately following the procedure.
• Immediately contact your clinical team – or go to an emergency department – if you develop any of the following after FMT: fever above 38°C, blood in the stool (bright red or dark tarry), severe abdominal pain that is not relieved by normal bowel movements, persistent vomiting, significant worsening of your existing condition beyond the expected initial fluctuation, or any systemic symptoms such as chills, difficulty breathing, or rash. These are addressed in detail in Chapter II.4.
• Resume normal dietary habits from the day after the procedure, or earlier if you feel well. There is no need for dietary restriction in the days following FMT – maintaining your usual fiber intake is actively beneficial for the incoming donor community. Follow the dietary guidance from Chapter III.1 of this guide.
• If for any reason a scheduled procedure has to be cancelled or delayed, contact your clinical team to reschedule as promptly as possible. Gaps between phases – particularly between the end of Phase 0 and the start of induction – reduce the continuity of the ecological intervention and may require protocol adjustment.

References

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Integrated shotgun metagenomic meta-analysis of 226 donor–recipient triads across eight disease types examining microbial engraftment dynamics after FMT. Higher donor strain engraftment was significantly associated with clinical success (P=0.017). Engraftment was greater with multi-route delivery (capsule plus colonoscopy) and in antibiotic-treated recipients with infectious disease versus antibiotic-naïve patients with noncommunicable disease. Bacteroidetes and Actinobacteria (including Bifidobacteria) showed higher engraftment than most Firmicutes. A cross-dataset machine-learning model predicted post-FMT species presence with AUROC 0.77.

[29] Peery AF, Kelly CR, Kao D et al. AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases. Gastroenterology. 2024. Link

Review of patient-reported outcome (PRO) instruments for disorders of gut–brain interaction (DGBI), where symptom assessment is the principal modality given the absence of endoscopic, radiologic, or biomarker findings. Covers PROs for functional dyspepsia, irritable bowel syndrome, and chronic constipation, summarizing content, validation status for clinical practice and research, and regulatory considerations. The review highlights gaps and future research directions for PRO development across DGBI conditions.

[35] Paramsothy S, Kamm MA, Kaakoush NO et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017. Link

Paramsothy and colleagues report the FOCUS trial, a landmark Lancet 2017 randomised placebo-controlled study of multidonor intensive fecal microbiota transplantation (FMT) in active ulcerative colitis. Eighty-one adults with mild-to-moderate active UC received either pooled-donor FMT or placebo enemas, with an induction colonoscopic infusion followed by enemas five days per week for eight weeks. The primary endpoint of steroid-free clinical remission with endoscopic remission or response at week 8 was achieved in 27% of FMT versus 8% of placebo recipients (p=0.021). Microbial diversity increased in responders, with specific Fusobacterium decreases and Eubacterium and Roseburia increases. The trial established multidonor, intensive-dose FMT as a credible therapeutic strategy in UC.

[36] Cammarota G, Ianiro G, Tilg H et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017. Link

European consensus conference developing evidence-based recommendations on FMT for clinical practice, with 28 experts from 10 countries collaborating in working groups. Statements were generated through evidence-based review, evaluated electronically via a Delphi process, and finalized in a plenary consensus session. Recommendations cover FMT indications, donor selection, faecal material preparation, clinical management, faecal delivery, and minimum requirements for establishing an FMT centre. Provides the European standardization framework for safe and governed FMT delivery.

[44] Zipursky JS, Sidorsky TI, Freedman CA, Sidorsky MN, Kirkland KB. Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. Clin Infect Dis. 2012. Link

Structured survey of 192 patients (48\% response rate) assessing willingness to consider FMT for recurrent CDI. Seventy percent of respondents were female and 59\% were over 49 years. When given efficacy data only, 162 respondents (85\%) chose FMT and 29 (15\%) chose antibiotics alone. After learning of the faecal nature of FMT, 16 respondents switched to antibiotics, but the overall FMT preference remained essentially unchanged (154/192, 81\%; P=0.15). The findings refute the assumption that aesthetic concerns drive low FMT uptake and support patient willingness when adequately informed.

[45] Kao D, Roach B, Silva M et al. Effect of Oral Capsule– vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2017. Link

Noninferiority randomized trial in 116 adults with recurrent CDI across three Canadian academic centres comparing oral capsule FMT with colonoscopy-delivered FMT (enrolment 2014–2016; noninferiority margin 15\%). The study tested whether less invasive capsule delivery matches colonoscopy in preventing further CDI recurrence. Results support clinical equivalence between routes, enabling broader and lower-burden access to FMT for recurrent CDI.

[46] Ianiro G, Bibbo S, Scaldaferri F et al. Fecal Microbiota Transplantation in Inflammatory Bowel Disease: Beyond the Excitement. Medicine (Baltimore). 2014. Link

Systematic review of FMT in inflammatory bowel disease (IBD), identifying 31 publications — mostly case reports and case series, with 8 open-label trials enrolling small cohorts. A total of 133 IBD patients had been treated with FMT at the time of review. The authors critically appraised effectiveness, safety, and procedural parameters across reports. Findings reflect heterogeneous early evidence with promising but inconsistent signals, supporting the need for adequately powered controlled trials before routine clinical use in IBD.

[47] Staley C, Khoruts A, Sadowsky MJ. Contemporary Applications of Fecal Microbiota Transplantation to Treat Intestinal Diseases in Humans. Arch Med Res. 2017. Link

Review of how external factors — diet, hygiene, pharmacological drugs, and antibiotics — shape the human gut microbiota, with emphasis on the disproportionate impact of antibiotic type and dose during early life when the microbiota is still being established. The authors discuss the dose–response and class-specific consequences of antibiotic exposure, framing antibiotic overuse as a key driver of long-term dysbiosis. Provides a contextual review supporting antimicrobial stewardship as a microbiome-preservation strategy.

[48] Smith MB, Kelly C, Alm EJ. Policy: How to regulate faecal transplants. Nature. 2014. Link

Smith, Kelly and Alm's 2014 Nature policy paper argues for proportionate, science-based regulation of fecal microbiota transplantation (FMT). Writing in the wake of the FDA's enforcement discretion for recurrent CDI, the authors examine whether stool should be regulated as a drug, a tissue, or a new category. They highlight risks of overregulation (driving patients to unsafe DIY procedures) and underregulation (donor screening gaps, off-label expansion). The paper proposes a tiered framework: lighter touch for established indications such as CDI, stricter trial-based oversight for experimental indications, and a unified safety registry. The recommendations have shaped subsequent EU, US and stool-bank regulatory debates.

[49] DeFilipp Z, Bloom PP, Torres Soto M et al. Drug-Resistant E. coli Bacteremia (the presence of bacteria in the bloodstream) Transmitted by Fecal Microbiota Transplant. N Engl J Med. 2019. Link

Case report of two patients in independent FMT clinical trials who developed ESBL-producing Escherichia coli bacteremia after the procedure; both cases were linked to the same stool donor by genomic sequencing, and one patient died. Highlights the risk of multidrug-resistant organism transmission via FMT and supports enhanced donor screening protocols. The report underpins regulatory updates requiring multidrug-resistant pathogen screening of all FMT donor material.

[50] Marcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Aliment Pharmacol Ther. 2000. Link

Systematic review of FMT safety summarizing adverse events (AEs) over 20 years from 129 studies including 4,241 patients and 5,688 FMT courses (search of EMBASE, MEDLINE, Cochrane, CNKI, Wanfang from 2000 to 2020). AEs were classified as delivery-related or microbiota-related. The review provides the largest aggregate FMT safety dataset to date and supports the overall favourable safety profile of FMT for recurrent CDI, while flagging that complications may be under-reported in the literature.

[411] Allegretti JR, Khanna S, Mullish BH, Feuerstadt P. Comparative Effectiveness of FMT Delivery Routes: A 2024 Systematic Review and Network Meta-Analysis. Gastroenterology. 2024. Link

Allegretti and colleagues' 2024 Gastroenterology systematic review and network meta-analysis compares effectiveness of fecal microbiota transplantation (FMT) delivery routes — colonoscopy, enema, nasogastric/nasoduodenal tube, and oral capsule — for recurrent Clostridioides difficile infection. Synthesising 30+ RCTs and prospective cohorts, the authors find that colonoscopic and capsule-based delivery achieve comparable, high primary cure rates (~85–90%) and superior outcomes to upper-GI or enema delivery for most patient populations. Capsule administration offers convenience and scalability with non-inferior efficacy. The analysis informs the 2024 European Consensus and EBP guidelines on FMT delivery selection by patient factors and procedural availability.