Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes

Abstract

INTRODUCTION: The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC. METHODS: Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing. RESULTS: The median maintaining time of the efficacy was 120 days (IQR, 45–180) and 182.5 days (IQR, 105–311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella , Lactobacillus , and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission ( P < 0.05). DISCUSSION: This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/CTG/A363 ).

Fecal Microbiota Transplantation as Therapy for Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis

“…Another study showed that sustained remission of UC patients was associated with butyrate-producing organisms, and relapse was associated with Proteobacteria and Bacteroidetes [ 27 ]. In addition, a recent prospective study demonstrated that the differences of the recipients' relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission [ 28 ]. As a result, selecting donors based on microbial indicators and/or capability of the donor microbiota may be important for improved FMT efficacy [ 7 ].…”

“…This method may resolve the bias between studies due to differences of stool dosage in the future. Additionally, a recent prospective study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits [ 28 ]. In terms of pretreatment antibiotics use, two trials [ 11 , 17 ] had antibiotic pretreatment as part of their methods, two trials [ 15 , 16 ] did not adopt the use of antibiotics prior to FMT, and one trial [ 18 ] did not report this item.…”

“…Another study showed that sustained remission of UC patients was associated with butyrate-producing organisms, and relapse was associated with Proteobacteria and Bacteroidetes [27]. In addition, a recent prospective study demonstrated that the differences of the recipients' relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical =0.00; Chi 2 = 0.24, df = 2 (P = 0.89); l 2 = 0% Heterogeneity: Tau 2 =0.01; Chi 2 = 1.09, df = 1 (P = 0.30); l 2 = 8% Heterogeneity: Tau 2 =0.00; Chi 2 = 1.34, df = 4 (P = 0.86); l 2 = 0% 26 29 Heterogeneity: Tau 2 =0.00; Chi 2 = 0.75, df = 2 (P = 0.69); l 2 = 0% Heterogeneity: Tau 2 =0.00; Chi 2 = 0.15, df = 1 (P = 0.69); l 2 = 0% Heterogeneity: Tau 2 =0.00; Chi 2 = 1.34, df = 4 (P = 0.86); l 2 = 0% Test for overall effect: Z = 3.54 (P = 0.0004) Test for overall effect: Z = 2.30 (P = 0.02) Test for overall effect: Z = 4.17 (P < 0.0001) Gastroenterology Research and Practice remission [28]. As a result, selecting donors based on microbial indicators and/or capability of the donor microbiota may be important for improved FMT efficacy [7].…”

“…This method may resolve the bias between studies due to differences of stool dosage in the future. Additionally, a recent prospective study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits [28]. In terms of pretreatment antibiotics use, two trials [11,17] had antibiotic pretreatment as part of their methods, two trials [15,16] did not adopt the use of antibiotics prior to 31 Heterogeneity: Tau 2 = 0.12; Chi 2 = 3.19, df = 1 (P = 0.07); l 2 = 69% Test for overall effect: Z = 0.68 (P = 0.50) Total (95% CI) 147 145 100.0% 0.91 [0.84, 0.99] Total events 124 137 Heterogeneity: Tau 2 = 0.00; Chi 2 = 4.26, df = 4 (P = 0.37); l 2 = 6% Test for overall effect: Z = 2.28 (P = 0.02) Test for subgroup differences: Chi 2 = 0.10, df = 1 (P = 0.75), l 2 = 0% 0.2 0.5 1 2 5 Favours FMT Favours control Heterogeneity: Tau 2 = 0.00; chi 2 = 4.26, df = 4 (P = 0.37); l 2 = 6% Test for overall effect: Z = 2.28 (P = 0.02) Test for subgroup differences: Chi 2 = 0.00, df = 1 (P = 0.95%), l 2 = 0% 50 57 124 137 9 Gastroenterology Research and Practice FMT, and one trial [18] did not report this item.…”

The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease

“…In an observational study by Li et al, 202 patients were followed after an FMT procedure for ulcerative colitis, with a second FMT treatment offered in case of relapse. The median time of sustained clinical response, defined as a decrease in partial Mayo score of 3 or more points and at least 20% from baseline, with a rectal-bleeding subscore of 0 or 1, and a decrease in the rectal-bleeding subscore by at least 1 after the first FMT procedure was 120 days; the median time of sustained clinical response after the second procedure was 182.5 days [ 106 ].…”