25 DONOR SELECTION OF FECAL MICROBIOTA TRANSPLANTATION IS IMPORTANT TO LONG-TERM MAINTENANCE OF ULCERATIVE COLITIS

2020 ◽  
Vol 158 (3) ◽  
pp. S59
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Term Maintenance ◽  
Selection Of

25 DONOR SELECTION OF FECAL MICROBIOTA TRANSPLANTATION IS IMPORTANT TO LONG-TERM MAINTENANCE OF ULCERATIVE COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S36-S36
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Age Difference ◽  
Maintenance Rate ◽  
Term Maintenance ◽  
Parent Child

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.

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 ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Post Treatment ◽  
Age Difference ◽  
Maintenance Rate ◽  
Term Efficacy ◽  
Term Maintenance

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.

scholarly journals Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations

2020 ◽  
Vol 8 (10) ◽  
pp. 1486
Author(s):  
Andrea Quagliariello ◽  
Federica Del Chierico ◽  
Sofia Reddel ◽  
Alessandra Russo ◽  
Andrea Onetti Muda ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Clinical Effects ◽  
Phylogenetic Distance ◽  
Fecal Microbiota Transplant ◽  
Inflammatory Bowel ◽  
Clinical Conditions ◽  
And Control

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.

scholarly journals An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel Ponce-Alonso ◽  
Carlota García-Hoz ◽  
Ana Halperin ◽  
Javier Nuño ◽  
Pilar Nicolás ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Clinical Success ◽  
Immunological Response ◽  
Organ Donor ◽  
Fecal Microbiota ◽  
Mucosal Immune Response ◽  
Donor Selection ◽  
Selection For

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient’s mucosal immune response against the donor’s microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient’s local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

scholarly journals Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongrong Ren ◽  
Xuefeng Gao ◽  
Yichao Shi ◽  
Jianfeng Li ◽  
Lihua Peng ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Bacteroides Fragilis ◽  
Fecal Microbiota ◽  
Low Intensity ◽  
Single Donor ◽  
Before And After

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.

P078 DONOR SELECTION INFLUENCES THERAPEUTIC EFFECTS OF FECAL MICROBIOTA TRANSPLANTATION FOR ULCERATIVE COLITIS

2020 ◽  
Vol 158 (3) ◽  
pp. S58-S59
Author(s):  
Keiichi Haga ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Kei Nomura ◽  
Shoko Ito ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Therapeutic Effects

scholarly journals Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

2021 ◽  
Author(s):  
Ying Wang ◽  
Jinhui Tang ◽  
Qingqing Lv ◽  
Yuxiang Tan ◽  
Xiaoxiao Dong ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Fecal Microbiota ◽  
Long Term Effects ◽  
Aged Mice ◽  
Gut Homeostasis ◽  
Term Maintenance

Fecal microbiota transplantation (FMT), a procedure in which fecal material is transferred from a donor to a recipient, has been increasingly used as a treatment to restore healthy gut microbiota. There is a substantial difference in the composition of gut microbiota between young and aged hosts, but little is known about whether age matching between the FMT donor and recipient affects microbiota restoration and long-term maintenance. In the present investigation, we aimed to study the establishment and resilience of transplanted gut microbiota in aged recipients. We treated naturally aged mice (20 months old) with a broad-spectrum antibiotic cocktail and monitored the restoration of gut microbiota over 8 weeks. The diversity of gut microbiota in aged mice failed to reach the baseline level via spontaneous recovery; in contrast, FMT from either (age-)matched or unmatched donors facilitated the recovery of gut microbiota diversity. The microbiota transplanted from different donors successfully established in the aged recipients and had long-term effects on the gene expression profiles of the host colon. Finally, we evaluated the long-term maintenance of transplanted microbiota via intentional disruption of gut homeostasis. We found that lack of age matching between FMT donors and recipients may decrease the resilience of transplanted gut microbiota against colonic inflammation. The results from our study systematically examining the effects of FMT on the gut homeostasis of aged hosts suggest that the compatibility between donors and recipients should be taken into account when implementing FMT.

P078 DONOR SELECTION INFLUENCES THERAPEUTIC EFFECTS OF FECAL MICROBIOTA TRANSPLANTATION FOR ULCERATIVE COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S36-S36
Author(s):  
Keiichi Haga ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Kei Nomura ◽  
Shoko Ito ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Antibiotic Therapy ◽  
Clinical Response ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
University Hospital ◽  
Controlled Study ◽  
Age Difference ◽  
Therapeutic Effects

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.

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