Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy

Haifer, Craig; Saikal, Aiasha; Paramsothy, Ramesh; Kaakoush, Nadeem O.; Leong, Rupert W.; Borody, Thomas J.; Kamm, Michael A.; Paramsothy, Sudarshan

doi:10.1136/gutjnl-2020-323581

Cited by 17 publications

(14 citation statements)

References 5 publications

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“…The first FMT studies on UC pointed to limited efficacy, although recent revisions (11, 23) observed higher remission when using high fecal dosage, regardless of the donor, and the previous administration of antibiotics; however, certain other variables might also be involved (24), as the duration and severity of the disease (11). None of our 4 patients showed relevant clinical improvement after FMT, which contrast with previous reports (25)(26)(27); however, the beneficial effects reported in those studies were not long lasting. Conversely, a recent study (28) provided evidence for the long-term efficacy of FMT in patients with UC, particularly associated with the increase in Proteobacteria and the decrease in Bacteroidota phyla.…”

Section: Discussioncontrasting

confidence: 80%

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

et al. 2021

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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.

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Section: Discussioncontrasting

confidence: 80%

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

et al. 2021

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“…19 Induction FMT does not appear to be durable for most patients with UC with subsequent disease relapse a median of 6 months post FMT. 22 There are limited data on the role of maintenance FMT in patients with UC, with only one RCT of 61 patients showing similar rates of clinical (87% vs 67%, P = 0.11), but higher rates of endoscopic and histologic remission at week 48 after colonoscopic FMT every 8 weeks compared with placebo. 23 One placebo controlled RCT to date has been performed to assess the role of FMT in maintaining remission in Crohn's disease, with only 17 patients included in the intention to treat analysis.…”

Section: Evidence For Use Of Fecal Microbiota Transplantation For Gastrointestinal Diseasesmentioning

confidence: 98%

An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases

Waller

Leong

Paramsothy

2021

J of Gastro and Hepatol

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Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.

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“…In a meta‐analysis, the safety and effectiveness of FMT for treating UC was reported 27 . Reportedly, FMT did not have a sustained effect on the treatment of UC patients unless the administration was repeated and prolonged 28 . The efficacy of FMT depends on microbial interactions between the donor and recipient strains 29 .…”

Section: Ibdmentioning

confidence: 99%

“… 27 Reportedly, FMT did not have a sustained effect on the treatment of UC patients unless the administration was repeated and prolonged. 28 The efficacy of FMT depends on microbial interactions between the donor and recipient strains. 29 The interactions between bacterial and metabolic pathways are also associated with the induction of remission.…”

Section: Ibdmentioning

confidence: 99%

Essential updates 2020/2021: Colorectal diseases (benign)—Current topics in the surgical and medical treatment of benign colorectal diseases

Shinmoto

Miyamoto

Yoshida

et al. 2022

Annals of Gastroent Surgery

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The development of new drugs for inflammatory bowel disease (IBD) is remarkable, and treatment strategies using multiple agents and various techniques are required; however, the treatment strategy is likely to be complex. Therefore, appropriate evaluation of traditional surgical treatment strategies and accurate knowledge of the efficacy and limitations of novel treatments are required. Total infectious complications were found to be associated with the use of corticosteroids and anti‐tumor necrosis factor‐α agents, but not with immunomodulators, anti‐integrin agents, and 5‐aminosalicylic acid. Regarding surgical procedures for IBD, conceived anastomosis methods, including Kono‐S for Crohn's disease stenosis, are associated with better outcomes than conventional techniques. Autologous cell transplantation for Crohn's fistulae has been shown to have a favorable outcome. Diverticulitis is increasing and will be treated more frequently in the future. Risk factors for the incidence of diverticulitis and differences in pathogenesis according to right or left side diverticulitis have been reported. Antibiotic therapy may be omitted for uncomplicated diverticulitis. Moreover, regarding surgical procedures, both bowel resection and anastomosis are associated with favorable short‐term outcomes, higher stoma closure rate, and superior medical economy compared to Hartmann's procedure. Risk factors for recurrence after diverticulitis surgery may provide better postoperative follow‐up. In this review, we explore the current topics of colorectal benign diseases, focusing on IBD and diverticulitis, based on clinical trials and meta‐analyses from 2020‐2021. This review consolidates the available knowledge and improves the quality of surgical procedures and perioperative management for IBD and diverticulitis.

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Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy

Cited by 17 publications

References 5 publications

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

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

An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases

Essential updates 2020/2021: Colorectal diseases (benign)—Current topics in the surgical and medical treatment of benign colorectal diseases

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