scholarly journals Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation

2020 ◽  
Vol 9 (6) ◽  
pp. 1650
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  

We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent–child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S36-S36
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  

Abstract Background Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for various disease. However, the therapeutic mechanism is still unclear. We previously demonstrated that fresh-fecal microbiota transplantation following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] for ulcerative colitis (UC) patients induced changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Here, we analyzed microbiota to examine the beneficial species, and observed long-term course (12 months) of the patients who treated with AFM and A-FMT. Moreover, we explore the concept of best donor for FMT success. Methods This prospective and non-randomized controlled study was conducted from July 2014 to March 2017 at Juntendo University Hospital. Eligible patients were at least 20 years of age, with a diagnosis of active UC which were required a Lichtiger’s clinical activity index (CAI) of 5 or more, or with an endoscopic Mayo score of 1 or more. Patients’ spouses or relatives in the family were selected as donors. AFM was administered to patients with UC for 2 weeks, and up to 2 days before fresh FMT. Clinical response was defined as a decrease of CAI of 3 points or more, and remission was defined as 3 points or less. Maintenance of efficacy was defined as no exacerbation of CAI and no intensification of treatments. Results Seventy-nine patients completed protocol (A-FMT; n = 47, mono-AFM; n = 32). At 4 weeks after treatment, clinical response and remission were observed in 31 and 19 patients (65.9%, 40.4%) in A-FMT, which higher than in mono-AFM respectively (56.2%, 18.7%). The maintenance rate of clinical responder was shown to be significantly higher in A-FMT than in AFM at 12 months after treatment (A-FMT vs mono-AFM, n = 13, 10; P = 0.046). Furthermore, in case that the age difference between donor and patient is more than 11 years, maintenance rate was significantly lower than 0–10 age difference in A-FMT (≧11 vs 0–10, n = 14, 16; P = 0.004). Siblings relationship has a significantly higher maintenance rate compared to parent–child relationship (Siblings vs parent-child; n = 7, 13; P = 0.009). An analysis of some cases in which the microbiota was followed for 24 months revealed a tendency that some bacterial species such as Bacteroides dorei and Bacteroides uniformis maintained their effects. Conclusion A-FMT exhibited reassuring clinical outcomes in terms of both short and long term. This is the first report of FMT to reveal importance of donor selection for long-term maintenance for UC.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S043-S044 ◽  
Author(s):  
D Ishikawa ◽  
K Okahara ◽  
M Takahashi ◽  
K Haga ◽  
K Nomura ◽  
...  

Abstract Background We previously demonstrated that fresh-faecal microbiota transplantation (FMT) following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] for ulcerative colitis (UC) patients induced changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Here, we analyse the short- and long-term efficacy of A-FMT comparing to AFM monotherapy, and we explore the concept of a beneficial donor for long-term maintenance. Methods This prospective and non-randomised control study was conducted from July 2014 to March 2017. Eligible patients were at least 20 years of age, with a diagnosis of active UC which were required a Lichtiger’s clinical activity index (CAI) of 5 or more, or with an endoscopic Mayo score of 1 or more. Patients’ spouses or relatives in the family were selected as donors. AFM was administered to patients with UC for 2 weeks, and up to 2 days before fresh FMT. Clinical response was defined as a decrease of CAI of 3 points or more, and remission was defined as 3 points or less. Maintenance of efficacy was defined as no exacerbation of CAI and no intensification of treatments. Results Seventy-nine patients completed protocol (A-FMT; n = 47, mono-AFM; n = 32). At 4 weeks after treatment, clinical response and remission were observed in 31 and 19 patients (65.9%, 40.4%) in A-FMT, which higher than in mono-AFM respectively (56.2%, 18.7%). The maintenance rate of clinical responder was shown to be significantly higher in A-FMT than in AFM at 12 months and 24 months after treatment (A-FMT vs. mono-AFM, p = 0.046 and 0.034, Wilcoxon test). In A-FMT, in case that the age difference between donor and patient is more than 11 years, maintenance rate was significantly lower than 0–10 age difference in A-FMT (≥11 vs. 0–10, n = 14, 16; p = 0.004 and p = 0.003, log-rank test). Siblings relationship has a significantly higher maintenance rate compared with parent–child relationship (Siblings vs. parent–child; n = 7, 13; p = 0.009 and p = 0.006, log-rank test). Conclusion A-FMT exhibited reassuring clinical outcomes in terms of short and long term. This is the first report of FMT to reveal the importance of matching between donors and patients for long-term maintenance on UC.


2020 ◽  
Vol 158 (3) ◽  
pp. S59
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S36-S36
Author(s):  
Keiichi Haga ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Kei Nomura ◽  
Shoko Ito ◽  
...  

Abstract Background We have recently reported the efficacy of combination of triple-antibiotic therapy and fecal microbiota transplantation (A-FMT) for patients with ulcerative colitis (UC). It has been reported that FMT with frozen donor faeces (frozen-FMT) is as effective as fresh-FMT for Clostridium difficile infection. However, it is still unclear which donor and condition is suitable for FMT on UC. The aim of this study was to evaluate the effectiveness of frozen-FMT compared to fresh-FMT, and verify effective conditions. Moreover, we explore the concept of best donor for A-FMT success. Methods This prospective and randomized controlled study was conducted from July 2017 to September 2019 at Juntendo University Hospital. Eligible patients were at least 20 years of age, with a diagnosis of active UC which were required a Lichtiger’s clinical activity index (CAI) of 5 or more, or with an endoscopic Mayo score of 1 or more. Patients were randomly allocated fresh or frozen faecesfrom 2 healthy donors. Triple-antibiotic therapy (Amoxicillin, Fosfomycin, Metronidazole; AFM) was administered to patients with UC for 2 weeks, and up to 2 days before FMT. Clinical outcomes were assessed at8 weeks and 1 year after treatment. Clinical response was defined as a decrease of CAI of 3 points or more, and remission was defined as 3 points or less. Maintenance of efficacy was defined as no exacerbation of CAI and no intensification of treatments. Results 29 patients completed protocol (fresh-FMT; n = 15, frozen-FMT; n = 14). At 8 weeks after treatment, clinical response and remission were observed in fresh-FMT (46.7%, 33.3%), and in frozen-AFM (64.3%, 42.9%) respectively.There were no significant differencesin therapeutic effectsbetween frozen-FMT and fresh-FMT.On the other hand, in cases which age difference between donor and patient was more than 16 years, maintenance rate was significantly lower than 0–15 age difference (0–15 vs ≧16, n = 14, 15 p<0.05). Interestingly,in cases that age difference between patient and donor was 0–15 years, high therapeutic effect was observed in patients treated withfresh- FMT. Conclusion This study showed that A-FMT with frozen faeces is as effective as cases treated with fresh faeces. In addition, findings from this study indicate that donor selection influences treatment effects, and age difference between patient and donor might be an important factor for A-FMT success.


2020 ◽  
Vol 8 (10) ◽  
pp. 1486
Author(s):  
Andrea Quagliariello ◽  
Federica Del Chierico ◽  
Sofia Reddel ◽  
Alessandra Russo ◽  
Andrea Onetti Muda ◽  
...  

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rongrong Ren ◽  
Xuefeng Gao ◽  
Yichao Shi ◽  
Jianfeng Li ◽  
Lihua Peng ◽  
...  

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria.Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT.Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group.Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Wai Ching Lam ◽  
Chen Zhao ◽  
Wen Juan Ma ◽  
Liang Yao

Background and Purpose. Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation. Methods. We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses. Key Results. A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P<0.001; I2=0%) and clinical response (OR, 2.75 [1.33, 5.67]; P=0.006; I2=49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P=0.37; I2=69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P=0.44; I2=0%). Conclusions and Inferences. Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.


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