FMT Fecal Microbiota Transplantation engraftment after budesonide or placebo in patients with active ulcerative colitis using pre-selected donors: a randomized pilot study (Apr 2024, n=24) "clinical response appeared donor-dependent"

[Michael Harrop]

https://academic.oup.com/ecco-jcc/advance-article/doi/10.1093/ecco-jcc/jjae043/7640395

Abstract​

Background
Fecal microbiota transplantation (FMT) shows some efficacy in treating patients with ulcerative colitis (UC), although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC.

Methods
Patients ≥ 18 years old with mild to moderate active UC were randomly assigned to three weeks budesonide (9 mg) or placebo followed by four weekly infusions of a donor feces suspension. Two donors were selected based on microbiota composition, Treg induction and SCFA production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical efficacy was assessed.

Results
In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment (p=0.56) nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 (42%) of patients achieved (partial) remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response (80% of responders, p<0.05) but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response.

Conclusion
In this small study, pretreatment with budesonide did not significantly influence engraftment or clinical response after FMT. However, clinical response appeared donor-dependent. Response to FMT may be related to transfer of specific strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic benefit in ulcerative colitis.

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From a set of 12 eligible fecal donors, a rational selection of the 2 donors used in this study (D07 and D08) was based on microbiota community composition, ability to induce T regulatory cells (Tregs) in vivo, and capacity to produce short-chain fatty acids (SCFAs) in vivo (see supplementary appendix for a more detailed description).

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These findings also suggest that selecting FMT donors based on in vitro, microbiome community, or animal model data alone may be insufficient to predict FMT clinical response in patients with IBD

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They have a section (3.4) on adverse events.

In total, 24 adverse events were observed [Table 3]. Of these, 16 events were listed as possibly related to FMT, such as abdominal cramps after infusion and constipation. Eight events were registered as not related to FMT, including: high blood pressure and high glucose level that were considered incidental findings and were treated by the general practitioner, weight gain that was attributed to cessation of smoking at the same time, stasis of food in the stomach resulting in the postponement of FMT by 1 week, and pain in a foot which was treated with paracetamol. Two cases of anaemia were attributed to ongoing inflammation and were treated with iron supplementation. None of the adverse events mentioned in Table 3 led to hospitalization.

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Very good that they listed them all with the reasons they classified them as unrelated, but I don't think they're all unrelated.


Follow-up study:
Dynamics of Gut Microbiota after Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae (Sep 2024, n=24) "Nine patients (38%) reached remission at week 14. The donor with the least engraftment was the most successful"