1 Moayyedi P.

et al. , 2 Rossen N.G.

et al. 1 Moayyedi P.

et al. 2 Rossen N.G.

et al. Two recent randomized controlled trials published in Gastroenterology indicated inconsistent results in the treatment of ulcerative colitis by fecal microbiota transplantation (FMT).Moayyedi et alreported a significant efficacy of FMT in inducing the remission of ulcerative colitis activity, with the 24% in FMT group compared with 5% in placebo group, whereas Rossen et alreported that there was no difference in clinical and endoscopic remission between the patients who received FMT with feces from healthy donor and patients who received FMT with autologous feces.

3 Cui B.

et al. , 4 Zhang F.M.

et al. The results of these clinical trials are important to this field. We believe the efficacy of FMT for the treatment of inflammatory bowel diseases (IBD), and our findingsfrom clinical trials on refractory IBD strongly support this hypothesis. This is the reason why we kept FMT as a rescue therapy for refractory IBD in our center. In the 2 randomized controlled trials, the results might be influenced by inconsistent study designs, including differences in the control groups, dose of original feces, delivering of microbiota, and frequencies of FMT. Although the 2 trials showed a rate of clinical remission with 24% and 41.2% in FMT group, respectively, it was difficult to judge the advantage or disadvantage of each FMT protocol.

5 Kamada N.

et al. 6 Kump P.K.

et al. In Rossen et al’s study, an unexpected response was apparent in the control group who received FMT with patients’ own feces (25% of patients achieved the primary endpoint), which was obviously higher than the control group (5%) who were infused with water in Moayyedi et al’s study. This phenomenon drew a consideration of the selection of control groups. As is well-known, patients with IBD are characterized by disturbed composition of intestinal microbiota.Infusion of patients’ own fecal microbiota should have no effect on or even exacerbate the activity of disease, although Rossen’s study seemed to controvert this hypothesis. Five of the 20 patients in the control group achieved the primary endpoint (clinical remission), and fecal microbiota analysis of the control group at 12 weeks after FMT showed a different direction and diversity compared with these patients’ basic microbiota composition. Therefore, we suspect that the microbiota in the infused suspension were not the same as the microbiota in freshly defecated feces. The 6 hours of exposure to aerobic conditions might have influenced the function or viability of certain kinds of microbiota. These changes could not be detected by 16sRNA gene sequencing, but would affect the composition of colonized microbiota after FMT and even result in special clinical findings. Kump et al’sand our previous FMT experience based on >300 cases (data not shown) had found a significant increase of Fusobacteria in some patients’ fecal samples after FMT, which was limited or undetectable, either in their basic feces before FMT or in related donor’s feces by sequencing. The mechanism could be explained by the long-term exposure of fecal microbiota to aerobic conditions, which would activate or cause the death of some bacteria, or inhibit relative competitive bacteria, and result in the increasing abundance of certain bacteria after being colonized and proliferated in the intestine by FMT. The different direction of microbiota change after infusing with patients’ autologous fecal suspension in Rossen et al’s trials also supported this hypothesis. Additionally, this might be the reason why a relatively high rate of adverse events was observed in the group with placebo using autologous feces.

7 Cui B.

et al. 7 Cui B.

et al. Both trials indicate that a better clinical response occurred in patients who received FMT with certain donor’s fecal suspension. We believe the source of feces and the preparation of fecal microbiota would affect the quality of fecal microbiota. Therefore, before we can identify a “perfect donor” or a “poor donor” exactly, what we can do is to prepare the fecal microbiota as soon as possible and then deliver them into the place (intestine) where they should be.With the assistance of our developed automatic system (GenFMTer) for fecal microbiota purification, the time of procedures from feces collection to infusion of purified fecal microbiota into patients’ intestine was <1 hour,which will be certainly helpful to diminish the influence of aerobic conditions on the diversity of live fecal microbiota.

In conclusion, we believe these findings highlight that the source of feces and the laboratory protocols could affect the quality of fecal microbiota, as well as the efficacy and the safety of FMT. We need a better understanding on the mechanism and the possible problems with the related procedures. It might be the methodology, not the concept of FMT, that is affecting clinical findings.

Article Info Publication History Footnotes Conflicts of interest The authors disclose no conflicts. Identification DOI: https://doi.org/10.1053/j.gastro.2015.05.065 Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved. ScienceDirect Access this article on ScienceDirect

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