Step 3: Structured Non-Responder Decision Tree
This stepwise decision tree walks you through non-response: first confirm it and find the cause, then correct lifestyle, switch donors, or intensify induction according to what's driving it.
Apply the following stepwise framework at the appropriate non-response timepoint for your indication.
▶ STEP 3.1 Confirm non-response against indication-specific definition (Step 1). If within assessment window — continue, do not act yet.
▶ STEP 3.2 Conduct differential diagnosis review (Step 2, Categories A–D). Identify primary and secondary contributing factors.
▶ STEP 3.3 Exposome audit: review Food and Symptom Diary for the full consolidation period. Identify any of: antibiotic exposure, OTC use, diet regression, sleep disruption, major stress event.
▶ STEP 3.4 — If Category C identified: Optimize exposome before modifying FMT protocol. Re-assess at +4 weeks. Many apparent non-responders convert to partial or full responders with exposome correction alone.
▶ STEP 3.5 — If Category A (engraftment failure): Option 1: Donor change. Review Phase 0 compatibility data; select alternative donor. Option 2: Intensified induction (additional colonoscopic session or high-dose capsule loading). Option 3: Both, sequentially.
▶ STEP 3.6 — If Category B (diagnosis): Pursue diagnostic workup before retreating. FMT retreatment of a misdiagnosed condition is ineffective and delays appropriate care.
▶ STEP 3.7 — If Category D (biological resistance): Discuss realistic response expectations. Consider adjunct therapies (biologics for IBD, psychological co-treatment for IBS, GLP-1 analogs for metabolic syndrome). FMT may still provide partial benefit even in biological non-responders.
Immediately escalate to treating physician and consider treatment suspension if any of the following occur:
- Severe adverse event: fever >38.5°C + bloody stool + abdominal pain
- Microbiota-confirmed multi-drug resistant organism emergence
- New diagnosis requiring immunosuppression change