FMT / Microbiome Transfer in UC
Working model: if UC in Paul’s frame is substantially a distal microbial-ecology + mucus-positioning failure (see central-theory, pathobiont-mucus-layer-ecology-uc, beneficial-commensals-butyrate-ecology-uc), then fecal microbiota transplantation (FMT) is the most direct experimental test of that hypothesis: it replaces the community wholesale rather than nudging one taxon. This page tracks the controlled evidence and why FMT belongs on the clinician-discussion list as a real research lever — not the “unregulated FMT” caution it was previously reduced to.
Evidence level: moderate (multiple RCTs, modest effect, heterogeneity). Safety: FMT is not a DIY procedure — donor screening and regulated material matter; DIY/unscreened FMT carries real infection risk.
What the controlled evidence shows
According to PubMed, three placebo/control-comparator randomized induction trials in active UC are positive but modest (number-needed-to-treat roughly 4–5):
- Moayyedi et al., Gastroenterology 2015 — weekly enema FMT ×6 vs water enema. Remission 24% (9/38) vs 5% (2/37). Trial stopped early for futility but reached significance; responders clustered to a single donor, and shorter disease duration responded better (3/4 with UC ≤1 year vs 6/34 with UC >1 year). DOI
- Paramsothy et al., Lancet 2017 — intensive multidonor FMT (colonoscopy then enemas 5×/week ×8 weeks) vs placebo. Steroid-free clinical + endoscopic remission/response 27% (11/41) vs 8% (3/40). Notably, presence of Fusobacterium spp. was associated with lack of remission. DOI
- Costello et al., JAMA 2019 — short-duration anaerobically prepared pooled donor FMT vs autologous. Steroid-free remission 32% (12/38) vs 9% (3/35); 5/12 responders held remission at 12 months. DOI
Why this matters for Paul’s model
- It tests the core hypothesis. A positive personal response would strongly support the microbial-ecology/positioning branch over a purely intrinsic-barrier or purely immune model.
- The Fusobacterium signal links FMT to the pathobiont branch. Paramsothy’s finding that Fusobacterium tracked with non-remission is the same organism flagged in pathobiont-mucus-layer-ecology-uc — consistent with “who is present and where” mattering more than diversity alone.
- Intensity and route look important. The positive trials used repeated dosing and (in two of three) multidonor/pooled material; single low-intensity dosing is weaker. For distal/proctitis disease, a rectal/enema route is mechanistically attractive and worth a specific clinician question (parallels the “distal disease needs distal delivery” logic in constipation-contact-time-pelvic-floor-uc).
- Disease duration may be a window. The Moayyedi duration signal suggests earlier disease may be more modifiable — relevant to prioritization.
Cautions / open questions
- Effects are modest and not durable by default; maintenance FMT evidence is weaker and protocols are unstandardized (donor, preparation, route, dosing).
- Do not DIY. This is a clinician/trial pathway; unscreened donor stool carries infection-transmission risk.
- Where does FMT sit relative to Paul’s current mesalamine/topical regimen (see current-care-plan)? It is adjunct/experimental, not a replacement for guideline therapy.