Dataset Information

Linking Strain Engraftment in Fecal Microbiota Transplantation With Maintenance of Remission in Crohn's Disease.

ABSTRACT:

Background & aims

Crohn's disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system, and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through fecal microbiota transplantation (FMT) is a promising approach for the treatment of CD.

Methods

We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species and link these events to the maintenance of remission in CD.

Results

We found that FMT had a significant long-term effect on patient microbial compositions, although this was primarily driven by the engraftment of donor species, which remained at low abundance. Thirty-eight percent of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods, such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, and transmission of Bacteroidetes was deleterious.

Conclusions

Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD.

SUBMITTER: Kong L

PROVIDER: S-EPMC7725862 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDonor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors.MethodsWe conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients' gut microbiomes.ResultsMulti-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains.ConclusionOur study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity.Trial registrationThe Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615001351505 ).Trial protocolThe trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.