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Key bacterial, metabolic changes linked to UC remission after FMT

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Patients with ulcerative colitis who underwent fecal microbiota transplantation showed consistently increased microbial diversity and altered microbiota composition, and specific bacterial and metabolic changes correlated with the likelihood of remission, according to new research presented at the 13th Congress of the European Crohn’s and Colitis Organisation.

In particular, the presence of Fusobacterium after FMT was associated with lack of remission, while changes in bacterial metabolic activity were associated with remission, according to Sudarshan Paramsothy, MD, of the University of South Wales, Australia, and colleagues.

“This report represents the largest and most comprehensive analyses of the bacterial taxonomic and functional changes associated with FMT in ulcerative colitis, derived from the largest trial to date in the field,” he told Healio Gastroenterology and Liver Disease.

The FOCUS study was a randomized placebo-controlled trial that showed multi-donor FMT was effective for treating patients with active ulcerative colitis. Efficacy results were previously reported in the Lancet and at Digestive Disease Week 2016.

For the current study, Paramsothy and colleagues assessed the bacterial taxonomic and functional changes associated with patient outcomes by sequencing 314 fecal and 160 colonic biopsy samples collected at different time points from 70 patients, as well as 113 fecal samples from 14 individual donors and 21 multi-donor batches. They also performed shotgun metagenomics on 285 fecal samples.

“FMT substantially increases microbial diversity and markedly changes microbial composition in UC patient recipients,” Paramsothy said. “These diversity changes appear to be more than just transient effects because (1) the changes were observed in both the resident and active (16S rRNA gene and transcript) fecal and mucosal microbiomes, (2) they are replicated using shotgun metagenomics, and (3) they are durable at 8 weeks after FMT cessation.”

Global microbial composition shifted from Bacteroides to Prevotella dominance after FMT, and Fusobacterium most consistently correlated with lack of remission (P = .028), as did Sutterella, Veillonella, and Haemophilus. While Firmicutes like Clostridium XVIII, Ruminococcus and Lachnospiraceae most commonly correlated with remission, these associations were less consistent.

The investigators noted that fecal and colonic mucosal microbiota were highly concordant.

Among donors, the presence of a Streptococcus OTU correlated with ineffective batches.

Finally, fecal shotgun metagenomics showed that changes in bacterial metabolic function following FMT — namely, shifts to starch degradation pathways and short-chain fatty acid production — correlated with remission. Conversely, heme biosynthesis correlated with lack of remission. Eubacterium, Ruminococcus, Lachnospiraceae, and Roseburia appeared to contribute to beneficial metabolic pathways.

These findings show that “specific bacterial taxa and metabolic pathways associated with FMT therapeutic outcomes in UC patients, both remission and treatment failure, with consistency between the taxonomic and functional changes,” Paramsothy said. “These findings may have important implications for donor and patient selection and shaping future bacterial therapy for UC.” – by Adam Leitenberger

Reference:

Paramsothy S, et al. Abstract OP019. Presented at: 13th Congress of ECCO; Feb. 14-17, 2018; Vienna.

Disclosures: Paramsothy reports grants during the conduct of the study from the Broad Medical Research Program at Crohn's & Colitis Foundation, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, and the University of New South Wales Gold Star Award. Please visit the ECCO website for all authors’ relevant financial disclosures.