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Clinical Trial
. 2016 Oct 20;128(16):2083-2088.
doi: 10.1182/blood-2016-05-717652. Epub 2016 Jul 26.

Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut

Kazuhiko Kakihana  1 , Yuki Fujioka  2   3 , Wataru Suda  4   5 , Yuho Najima  1 , Go Kuwata  6 , Satoshi Sasajima  7 , Iyo Mimura  8 , Hidetoshi Morita  8 , Daisuke Sugiyama  2 , Hiroyoshi Nishikawa  2 , Masahira Hattori  4   9 , Yutaro Hino  1 , Shuntaro Ikegawa  1 , Keita Yamamoto  1 , Takashi Toya  10 , Noriko Doki  1 , Koichi Koizumi  6 , Kenya Honda  5   7   11 , Kazuteru Ohashi  1
Affiliations
Clinical Trial

Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut

Kazuhiko Kakihana et al. Blood. .

Abstract

Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.

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Figures

Figure 1
Figure 1
Components of microbiota and immunological assay. (A) Temporal dynamics of the microbiota (at the genus level) and clinical course in each patient: (i) case 1, (ii) case 2, (iii) case 3, and (iv) case 4. *1: Data from the day after first FMT could not be obtained because of the lack of fecal sample. (B) (i) Subpopulation of Tregs. Tregs can be dissected into 3 subpopulations by expression levels of FoxP3, CD45RA. FoxP3loCD45RA+ cells (fraction 1), designated as naive Tregs, which differentiate into eTregs under antigenic stimulation; FoxP3hiCD45RA− cells (fraction 2), designated eTregs, which are terminally differentiated and highly suppressive; and FoxP3loCD45RA− non-Tregs (fraction 3), which do not possess suppressive activity, but secrete proinflammatory cytokines. (ii) The absolute number of eTregs (red lines) and the eTreg/CD8+ T-cell ratio (green lines) in peripheral blood of each patient. CAZ, ceftazidime; CFPM, cefepime; FK, tacrolimus; Fr, fraction; LVFX, levofloxacin; MEPM, meropenem; PSL, prednisolone; ST, sulfamethoxazole/trimethoprim; TAZ/PIPC, tazobactam/piperacillin; TEIC, teicoplanin; VCM, vancomycin.
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Comment in

  • Fit for cure? Microbiota and GVHD.
    Holler E, Weber D. Holler E, et al. Blood. 2016 Oct 20;128(16):2004-2005. doi: 10.1182/blood-2016-08-732156. Blood. 2016. PMID: 28157678 No abstract available.

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