Lingjia Kong1, Jason Lloyd-Price2, Tommi Vatanen3, Philippe Seksik4, Laurent Beaugerie5, Tabassome Simon6, Hera Vlamakis2, Harry Sokol7, Ramnik J Xavier8. 1. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 2. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts. 3. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts; Liggins Institute, University of Auckland, Auckland, New Zealand. 4. Centre de Recherche Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Service de Gastroenterologie, Sorbonne Université, INSERM 75012, Paris, France; Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique-Hopitaux de Paris, Paris, France; French Group of Fecal Transplantation, Paris, France; Paris Center for Microbiome Medicine, Paris, France. 5. Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique-Hopitaux de Paris, Paris, France; Paris Center for Microbiome Medicine, Paris, France. 6. Clinical Research Platform, Assistance Publique-Hopitaux de Paris Saint-Antoine Hospital, Paris, France; Department of Clinical Pharmacology, Assistance Publique-Hopitaux de Paris, Saint Antoine Hospital, Paris, France. 7. Centre de Recherche Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Service de Gastroenterologie, Sorbonne Université, INSERM 75012, Paris, France; Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique-Hopitaux de Paris, Paris, France; French Group of Fecal Transplantation, Paris, France; Paris Center for Microbiome Medicine, Paris, France. Electronic address: harry.sokol@aphp.fr. 8. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts. Electronic address: xavier@molbio.mgh.harvard.edu.
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.
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.
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