Linking strain engraftment in fecal microbiota transplantation with maintenance of remission in Crohn's disease.

Abstract Background and 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 find that FMT had a significant long-term effect on patient microbial compositions, though this was primarily driven by the engraftment of donor species which remained at low abundance. 38% 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, while transmission of Bacteroidetes was deleterious. Conclusion Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and thus 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.