6. Warning Signs
FMT is safe, but a handful of signs — fever, bloody stool, severe abdominal pain, difficulty breathing — call for immediate emergency care.
Call emergency services or go to the emergency department immediately if any of the following is present:
- Fever ≥38°C
- Bloody stool (bright red or black, tarry)
- Severe, unrelenting abdominal pain
- Chills or rigors
- Difficulty breathing
- Lip or tongue swelling
- Skin rash or urticaria
- Loss of consciousness or collapse
DO NOT wait for your next scheduled appointment. Call your clinical team IMMEDIATELY or go to the emergency department.
Why This Chapter Exists – The Cost of Misclassification
In 1901, Harvey Cushing, a twenty-nine-year-old American surgeon who had just returned from studying with Theodor Kocher in Bern, introduced a practice to the operating theatres of Johns Hopkins Hospital that was, at the time, unusual: he recorded the patient's pulse and respiration rate continuously throughout surgery and plotted the measurements on a chart. This was the first systematic use of what would become the anaesthetic record and, eventually, the vital signs chart that is now standard in every hospital in the world. Cushing's insight was not that the measurements themselves were new – physicians had taken pulses for centuries. It was that change over time was the signal, and that a chart made change visible before it became crisis. The principle has not changed in 120 years. A single abnormal reading is noise. A trend is information. The warning sign framework in this chapter is built on the same logic: not to alarm patients with every symptom, but to distinguish the expected turbulence of colonisation from the narrower set of patterns that require clinical attention before they become something harder to reverse.
Every FMT patient will experience symptoms in the days and weeks after treatment. The preceding chapters have described what is normal and expected: loose stools, bloating, fatigue, cramping, and temporary appetite changes are part of the ecological reorganization process and do not require medical intervention. However, a small but clinically important subset of post-FMT symptoms are not normal, not self-limiting, and not safe to wait out. These warning signs require prompt medical contact regardless of time of day, day of the week, or how mild they initially appear.
The clinical cost of misclassifying a warning sign as a normal response is potentially severe: unrecognized bacteremia (the presence of bacteria in the bloodstream; a rare but serious complication), sepsis, intestinal perforation, severe allergic reaction, or pathogen transmission can progress rapidly to life-threatening states in the hours between symptom onset and medical contact. Conversely, the cost of reporting a genuine warning sign promptly is minimal: a phone call, a clinical assessment, and in most cases reassurance and continued treatment. The asymmetry of these outcomes means that the threshold for contacting the clinical team should always be low. When in doubt, report.
This chapter organizes warning signs into two categories: Emergency signs requiring immediate emergency department attendance or calling emergency services (Tier 1), and Urgent signs requiring same-day clinical contact with the FMT team during or outside office hours (Tier 2). Both tiers are described with their clinical mechanisms, their distinguishing features from normal post-FMT responses, and the actions required. A quick-reference table is provided for use during the treatment period.
Tier 1 – Emergency: Attend Emergency Department or Call Emergency Services Immediately
Fever ≥38°C. A temperature of 38°C or above at any point during the FMT treatment course is a Tier 1 warning sign. Fever after FMT may indicate bacteremia (translocation of donor or recipient bacteria into the bloodstream), sepsis, aspiration pneumonia (a rare complication of upper GI delivery routes), or transmission of a donor pathogen not detected by standard screening protocols [36], [50]. Mild temperature elevation up to 37.5°C for less than 24 hours without other systemic symptoms, resolving spontaneously, may represent a transient immune response and is classified as an expected normal response (see Chapter II.4). Any temperature at or above 38°C, or any fever accompanied by chills, rigors, sweating, confusion, or rapid heart rate, requires immediate emergency assessment regardless of its apparent magnitude. Do not take antipyretics to bring the temperature below the threshold and then wait – the underlying process that generated the fever requires clinical evaluation.
Blood in stool. The presence of visible blood in the stool at any point after FMT is a Tier 1 warning sign. Bright red blood suggests lower GI bleeding (rectal, sigmoid, or descending colon origin). Dark, tarry, or black stool (melaena) suggests upper GI bleeding. In the context of FMT, rectal bleeding may reflect mucosal injury from the colonoscopic procedure itself, exacerbation of pre-existing colitis, ischemic colitis, or, rarely, pathogen-related mucosal damage [50], [29]. Stool that is darker than usual but not overtly bloody – a common normal finding in the first 3–5 days reflecting altered bile acid metabolism and transit time – is not included in this warning sign. The distinguishing feature is visible fresh or altered blood on the toilet paper, in the toilet bowl, or mixed through the stool. In patients with established inflammatory bowel disease who have a prior history of mild rectal bleeding, the clinical team will have discussed the specific threshold for reporting at the pre-FMT assessment; follow those individualized instructions.
Severe or unremitting abdominal pain. Mild to moderate cramping that is wave-like, relieved by passing gas or stool, and not constant is a normal first-week finding. Severe abdominal pain that is constant rather than episodic, is not relieved by defecation or flatulence, is progressively worsening over hours, or is accompanied by abdominal rigidity or rebound tenderness is a Tier 1 warning sign. These features may indicate intestinal obstruction, perforation (a rare but serious complication of colonoscopic FMT), ischemic colitis, or a severe inflammatory flare [50], [29]. Pain radiating to the back or right shoulder tip warrants particular urgency, as these patterns may indicate diaphragmatic or retroperitoneal involvement.
Rigors, chills, and signs of systemic sepsis. Rigors – uncontrollable shaking chills that last more than a few minutes and are accompanied by fever – are a classic presentation of bacteremia and require emergency assessment. Additional systemic sepsis signs that require immediate emergency department attendance include: confusion or altered mental state; rapid heart rate (>100 beats per minute) at rest; rapid breathing (>20 breaths per minute); severe fatigue that prevents standing or normal activity; and pallor, mottled skin, or cold extremities. These signs may occur in the absence of a clearly elevated temperature in patients who are immunosuppressed or on steroids, and their absence of fever does not reduce their clinical significance [36], [65].
Allergic reactions and anaphylaxis. Allergic reactions to FMT preparations are rare but documented in the literature, with case reports of anaphylaxis to donor-specific protein components or excipients in capsule formulations [66]. Signs of a systemic allergic reaction requiring emergency attendance include: urticaria (hives – raised, itchy wheals on the skin); angioedema (swelling of the lips, tongue, throat, or face); difficulty swallowing or breathing; stridor (a high-pitched breathing sound); sensation of throat tightening; and cardiovascular collapse (dizziness, loss of consciousness, severe hypotension). Patients with known severe allergies should ensure they have an adrenaline auto-injector (EpiPen) accessible during treatment and should inform their clinical team at the pre-FMT assessment. Mild localized flushing or warmth after capsule intake that resolves within 1–2 hours is a normal vasomotor response and does not require emergency attendance.
Aspiration during upper GI delivery. For patients who receive FMT via nasogastric or nasoduodenal tube, aspiration of the preparation into the respiratory tract is a recognized serious adverse event, with an estimated incidence of approximately 0.3% in published case series [50]. Signs of aspiration include: immediate coughing or choking during or after the procedure; shortness of breath or wheeze developing within hours of the procedure; new-onset fever in the 24–48 hours following upper GI delivery; and productive cough with discoloured sputum. Any of these signs after upper GI delivery should be treated as a Tier 1 emergency.
Warning Sign Quick Reference Table
| Symptom / sign | Tier 1 – Emergency department / ambulance | Tier 2 – Same-day clinical contact |
|---|---|---|
| Fever | ≥38°C at any time; fever + chills, rigors, confusion, rapid pulse | 37.5–38°C not resolving after 24 h; recurring subjective fever sensation without measured temperature |
| Blood in stool | Visible fresh blood (bright red) or melaena (black, tarry) in stool at any time | Stool darker than usual persisting beyond day 5; symptoms suggesting occult bleeding without visible blood |
| Abdominal pain | Constant, progressive pain not relieved by gas/defecation; abdominal rigidity or rebound tenderness; pain radiating to back or right shoulder | Prolonged moderate cramping beyond day 5; new pain not matching expected profile |
| Signs of systemic sepsis | Rigors (uncontrollable shaking chills); confusion or altered mental state; rapid breathing (>20/min); rapid pulse (>100/min) at rest; sudden severe fatigue preventing standing | Subjective 'feeling unwell' not matching expected profile; asymptomatic rapid pulse |
| Allergic reaction | Urticaria (hives); angioedema (swelling of face, lips, throat); difficulty breathing; stridor; palpitations; cardiovascular collapse | Mild generalised flushing after capsule intake not resolving within 2 h |
| Aspiration after upper GI delivery | Coughing/choking during or after procedure; breathlessness or wheeze within hours of procedure; productive cough within 24–48 h of upper GI delivery | – |
| Worsening of underlying condition | Signs of fulminant colitis; symptoms of obstruction; rapidly progressive worsening without any improvement beyond 7–10 days | Moderate worsening persisting beyond 7 days without improvement; return toward pre-FMT severity level |
| Antibiotic prescription | – | Any antibiotic prescribed for any reason during the FMT course – notify clinical team same day (not an emergency requiring out-of-hours contact unless antibiotic is urgently needed) |
| Unexplained new symptoms | Neurological symptoms (confusion, severe headache, visual changes); cardiorespiratory symptoms; jaundice; dark cola-coloured urine | Any new symptom outside the expected profile that is not an immediate emergency |
Table 8 – FMT warning sign quick reference guide # Tier 1 signs require emergency services or immediate emergency department attendance. Tier 2 signs require same-day clinical contact with the FMT team during or outside office hours. Keep this table accessible throughout the treatment period.
Tier 2 – Urgent: Contact the FMT Clinical Team on the Same Day
Symptoms that do not require emergency attendance but require same-day contact with the FMT clinical team: Persistent vomiting. Mild nausea in the first 1–2 days after colonoscopic FMT or after taking larger capsule doses is a normal response. Persistent vomiting – defined as three or more vomiting episodes within a 24-hour period, or vomiting that prevents maintaining adequate fluid intake for more than 12 hours – requires same-day clinical contact. In the context of FMT, vomiting may indicate gastroparesis exacerbated by altered motility signalling, obstruction, or in capsule FMT, premature gastric dissolution of capsules delivering higher-than-expected microbial loads to the gastric mucosa [7]. The primary clinical concerns with persistent vomiting are dehydration and inability to maintain the capsule dosing schedule; both require clinical rather than self-management. Worsening diarrhoea beyond day 5. Diarrhoea or loose stools in the first 3–5 days after FMT are expected. Worsening, non-improving diarrhoea persisting beyond day 5, or diarrhoea that is severe (more than 6–8 loose stools per day) and not decreasing, requires same-day clinical contact. In the CDI context specifically, refractory or worsening diarrhoea after FMT may indicate incomplete pathogen elimination, a resistant CDI strain, or reinfection from an environmental source, and requires stool testing and clinical reassessment [36], [29]. In non-CDI patients, sustained severe diarrhoea may reflect an unfavourable compatibility signal or a donor-preparation-related inflammatory response. Significant worsening of the underlying condition. Mild, transient worsening of FMT symptoms in the first 1–2 weeks – particularly in inflammatory bowel disease – is within the expected range and has been documented in 20–35% of patients in the early consolidation phase (see Chapter II.5). Severe, rapidly progressing worsening that shows no signs of improvement beyond 7–10 days, or worsening that represents a quantitative rather than qualitative change in existing symptoms, requires same-day clinical contact. Examples include: the development of high-volume bloody diarrhoea in a patient with quiescent Crohn's disease; new abdominal mass or obstructive symptoms in an IBD patient with previously controlled rectal disease; or signs of fulminant colitis in a patient treated for recurrent CDI. Any newly prescribed antibiotic from any prescriber. Antibiotics prescribed for any indication during the FMT treatment course – by any prescribing physician, not only the FMT team – represent a significant threat to engraftment continuity and require immediate notification of the FMT clinical team. This is not an emergency requiring out-of-hours contact, unless the antibiotic is urgently needed and the clinical team is unavailable during normal working hours. The FMT team needs to know: the antibiotic name and dose, the indication, the expected course duration, and the timing relative to the last FMT dose. This enables protocol modification (dosing pause, extended washout, potential re-induction planning) that can substantially reduce the ecological damage of the antibiotic course. Any unexplained new symptom not included on the expected response list. The expected post-FMT symptom profile is well-defined and described in detail in Chapter II.4 and this chapter's tables. Any symptom outside this defined expected profile – particularly neurological symptoms (new confusion, severe headache, visual changes), cardiorespiratory symptoms (chest pain, new palpitations, unexplained shortness of breath), dermatological symptoms (new widespread rash, jaundice), or urological symptoms (dark cola-coloured urine, significant oliguria) – should be reported to the clinical team on the same day. While most such symptoms are unlikely to be directly FMT-related, the temporal association warrants clinical assessment to exclude the possibility related to rare but documented adverse events including bacteraemia-associated organ involvement and immune-mediated reactions [36], [50], [65].
- Persistent vomiting
- Worsening diarrhoea beyond day 5
- Significant worsening of the underlying condition
- Any newly prescribed antibiotic
- Any unexplained new symptom not on the expected response list
- Any symptom causing uncertainty
High-Risk Populations – Modified Reporting Thresholds
Certain patient populations carry a higher baseline risk for serious FMT-related adverse events and should apply lower reporting thresholds throughout the treatment course. These groups were identified in a 2021 systematic review analysing 4,241 FMT procedures as disproportionately prone to serious adverse events [50].
Immunocompromised patients – including those receiving systemic corticosteroids above physiological replacement doses, biologic immunosuppressants, chemotherapy, or post-transplant immunosuppression – are at elevated risk for bacteraemia, pathogen transmission events, and immune-mediated reactions. For these patients, the threshold for Tier 1 emergency attendance should be a fever of 37.8°C or above (rather than 38°C), any new systemic symptom occurring within 72 hours of an FMT dose, or any change in clinical status not consistent with expected post-FMT responses.
Patients with severe underlying IBD, active mucosal inflammation, or compromised intestinal barrier function are at elevated risk for bacterial translocation. In these patients, even mild systemic symptoms (low-grade fever, unexplained fatigue, new joint symptoms) in the post-FMT period warrant same-day clinical contact rather than watchful waiting.
Elderly patients (over 75 years) may present with atypical systemic infection symptoms – confusion, falls, or functional decline without classic fever – that require clinical assessment rather than home monitoring. Caregivers of elderly FMT patients should be briefed on these atypical presentations before treatment begins.
Microbiota Effects
- Post-FMT bacteraemia – translocation of donor or recipient bacteria into the bloodstream – is a rare but documented serious adverse event; it occurs more frequently after colonoscopic FMT in patients with pre-existing mucosal barrier compromise (IBD, cirrhosis, severe CDI), with an estimated frequency of approximately 0.5–1% in high-risk populations compared to
References
[7] van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013. Link
Open-label RCT in patients with recurrent C. difficile infection comparing duodenal donor faeces infusion (after short vancomycin + bowel lavage) with standard 14-day vancomycin, with or without bowel lavage. The primary endpoint was diarrhoea resolution without relapse at 10 weeks. The trial was stopped early at interim analysis: 13/16 patients (81\%) in the FMT arm achieved resolution after a single infusion, substantially exceeding both vancomycin arms. Establishes FMT as superior to antibiotic monotherapy for recurrent CDI and provides the landmark evidence base for FMT clinical translation.
[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.
[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.
[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.
[65] Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016. Link
Mechanistic review of FMT in recurrent C. difficile infection summarizing the proposed mechanisms of action: direct competition between C. difficile and commensals introduced by FMT, restoration of secondary bile acid metabolism (which inhibits C. difficile germination), and repair of the gut barrier through mucosal immune stimulation. The review consolidates the mechanistic basis for FMT in CDI and highlights translational implications for engineered microbial therapeutics targeting these pathways.
[66] Hibberd AA, Lyra A, Ouwehand AC et al. Intestinal microbiota is altered in patients with colon cancer and precancerous lesions. BMC Gastroenterol. 2017. Link
Hibberd and colleagues report in BMC Gastroenterology that the gut microbiota is altered in patients with colorectal cancer (CRC) and precancerous lesions. In a case-control study comparing CRC patients, adenoma patients and healthy controls using 16S rRNA gene sequencing, they observe reduced butyrate-producing Firmicutes (Roseburia, Faecalibacterium) and enrichment of Fusobacterium nucleatum and certain Bacteroides taxa in CRC. Adenoma microbiota was intermediate, suggesting progressive dysbiosis along the adenoma–carcinoma sequence. The authors discuss microbial biomarkers for early detection and the potential role of pro-inflammatory taxa in CRC pathogenesis. The work supports microbiota-informed CRC screening research.