From the Journals

Fecal microbiota transplants: Finding new microbial markers for donor efficacy in UC



Donor microbiota stability and species evenness, along with presence of certain microbial species, may predict donor efficacy in fecal microbiota transplantation (FMT) for the treatment of patients with ulcerative colitis (UC), a new study suggests.

The authors noted that these markers of donor efficacy could be used to optimize selection of donors to treat patients with UC and improve outcomes.

The investigators hypothesized that “there are features beyond microbial richness, individual bacterial species, and specific metabolites that may aid in successful identification of effective donors.” They published these findings in Gut.

The LOTUS clinical trial explored the efficacy of lyophilized FMT in patients with UC, but was cut short because of the COVID-19 pandemic. The study investigators analyzed fecal samples from the two donors enrolled in the trial to identify functional and taxonomic differences within the donors’ microbiota that have clinical relevance to their efficacy in active UC. Donor 1’s samples showed 100% efficacy among patients with UC, while donor 2’s samples showed 36% efficacy.

In donor 1, the researchers observed “robust stability in species richness” during the sampling periods, whereas donor 2 exhibited larger fluctuations. Although the species richness was significantly greater in the donor 2, the researchers reported that donor 1 exhibited significantly greater diversity at the higher taxonomic level of phylum. According to the investigators, this was reflected by the detection of Euryarchaeota, Synergistetes, and Verrucomicrobia in donor 1 but not in the second donor.

Despite a higher species richness in donor 2, the researchers found that a higher rate of uniquely classified metagenome-assembled genomes was produced per sample in the donor 1, which indicates greater species evenness, the second marker of efficacy according to investigators.

Blautia wexlerae was a highly prevalent metagenome-assembled genome that was enriched in donor 1 compared with donor 2, and the researchers reported that “a taxon with high similarity (OTU215) showed evidence of engraftment in patients receiving donor 1.” In addition, B. wexlerae demonstrated a trend toward enrichment in donor 2 samples that were associated with positive outcomes in patients and demonstrated evidence of engraftment in patients who received donor 2.

Ninety bacterial species as well as one archaeon were differentially abundant between donors, including 44 donor samples which were greater than 0.1% in relative abundance. According to the researchers, 17 out of the 44 species were enriched in the effective donor, with 11 (64.7%) assembled into high-quality genomes highly prevalent in that donor and 6 that demonstrated evidence of engraftment in patients.

Lastly, the investigators sought to validate the observed associations between certain microbial taxa and donor clinical efficacy in an independent cohort. In this analysis, the investigators evaluated shotgun metagenomics data of donors used to treat patients with UC and examined relative abundances against patient outcomes. Species associated with treatment success included Ruminococcus bromii, B. wexlerae, Eubacterium hallii, Coprococcus catus, Fusicatenibacter saccharivorans, and Parabacteroides merdae.

“We identified microbiota stability and species evenness as markers of donor efficacy, as well as specific microbial species that could be employed to improve donor selection and build artificial microbial consortia to treat UC,” the investigators concluded.

Given that the study enrolled only two donors, the generalizability of the findings may be limited. The researchers wrote that another limitation of the data analysis was “the bias towards more relatively abundant taxa due to the inability to assemble genomes from low-abundance species.” The lack of prospective validation studies on the novel metrics is another limitation of the study.

Some investigators disclosed relationships with biomedical companies, such as Takeda and Janssen.

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