Response to faecal microbiota transplantation in UC

In a substudy of STOP-Colitis, response to faecal microbiota transplantation (FMT) in ulcerative colitis (UC) patients was associated with a significant increase in mucosal gut-homing Treg cells and butyrate metabolism, along with a reduction in Th17 cells and multiple anti-microbial and pro-inflammatory pathways [1].

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.

1. 
   
   1. Quraishi MN, et al. ECCO-IBD 2020, OP09.
   
   
   2. Gogokhia L, et al. ECCO-IBD 2020, OP40.
   
   
   3. Jacob V, et al. Inflamm Bowel Dis. 2017;23(6):903-11.

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Posted on 14 April, 20205 January, 2021