STOP-Colitis was a prospective, open-label pilot study of FMT in UC. In a substudy, changes in host colonic mucosal immune cell subsets and gene expression following FMT were explored. Participants received 8 FMT infusions over 8 weeks; of 17 patients, 12 completed 8 weeks of FMT per protocol.
Response, defined by a reduction in Mayo score, was seen in 8 of 12 patients (67%). As first author Dr Mohammed Quraishi (University Hospital Birmingham, UK) explained, FMT responders showed a significant increase in Treg cells (Δ 5.02%; P<0.01), especially in effector-memory Treg cells (Δ 12%; P<0.001) and gut-homing Treg cells (Δ 18.55%; P<0.01). Immunophenotyping of peripheral blood mononuclear cells revealed a significant increase in IL-10 producing CD4 cells (Δ 2.16%; P=0.04), suggesting induction of peripheral immune tolerance which is preferentially compartmentalised to the colonic mucosa. Responders also had a significant reduction in mucosal Th17 cells (Δ −7.61%; P=0.017), IL-17 producing CD4 cells (Δ −7.69%; P=0.05), and CD8 cells (Δ -5.18%; P=0.04). Additionally, response was associated with a significant downregulation of host antimicrobial defence response, and with a significant upregulation of butyrate and propionate (2 short-chain fatty acids) metabolic pathways.
In another study, Dr Lasha Gogokhia (Weill Cornell Medicine, New York, USA) and colleagues attempted to unravel the mechanisms of clinical response to FMT by identifying a distinct, immune-reactive, core transferable microbiota [2]. This study provides a framework for the rational selection of immune-reactive microbiota for microbial therapy in inflammatory bowel disease (IBD). They used samples from their pilot FMT study in UC patients responsive to a single delivery of high-diversity faecal microbiota preparation [3]. To define the core transferable microbiota, metagenomic sequencing of donor, recipient, and 4-week post-FMT faecal samples was performed. To define the transferable immune-reactive microbiota (TIM), IgA-sequencing was also performed on these samples. Using a pre-clinical mouse model of colitis, the mechanistic impact of these TIM in shaping mucosal immunity and in guiding the response to UC was defined.
Results showed distinct TIMs in responders mediating iTreg protection. These TIM were found to induce IgA in a T-cell independent manner. TIM induction of IL-10 regulated both T-cell and non-T-cell mediated protection.
- Quraishi MN, et al. ECCO-IBD 2020, OP09.
- Gogokhia L, et al. ECCO-IBD 2020, OP40.
- Jacob V, et al. Inflamm Bowel Dis. 2017;23(6):903-11.
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Table of Contents: ECCO 2020
Featured articles
Gut Microbiome as Treatment Target
Response to faecal microbiota transplantation in UC
Bioactives produced by gut bacteria to modulate immune response
Big Data Analysis
Multi-omics help describe CD phenotypes
The positive impact of genetic data on drug development
Experimental Therapies: Study Results
AMT-101: an oral human IL-10 fusion protein
Phase 2 results of first-in-class TL1A inhibitor
Open-label extension study of risankizumab: final results
Clinical remission after dose escalation of upadacitinib
Short- and Long-Term Treatment Results
Infliximab discontinuation increases relapse risk
Tofacitinib ‘real-world’ effectiveness in active UC
Subcutaneous ustekinumab as maintenance therapy in UC
Subcutaneous vedolizumab maintenance therapy in CD
Vedolizumab treatment persistence and safety
Specific Therapeutic Strategies
Impact of strategies on intestinal resection rate
Early ileocaecal resection in CD patients failing conventional treatment
Biologics before surgery in IBD do not elevate infection risk
Top-down infliximab superior to step-up in children with CD
High versus standard adalimumab in active UC
Head-to-Head Comparison of Treatments
Vedolizumab and anti-TNF therapies: a real-world comparison
Cancer Risk
Increased risk of small bowel cancer in IBD
Increased incidence of colorectal cancer and death in CD
Risk of rectal, anal cancer increased in perianal CD
Glyco-fingerprint as risk factor of UC-associated cancer
Miscellaneous Topics
Resolution of mucosal inflammation has dramatic effect
PICaSSO validated in real-life study
Re-inducing inflammation in organoids from UC patients
Role of immune cells in intestinal fibrosis
Association between meat consumption and IBD risk
CD exclusion diet corrects dysbiosis
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