title: Complete suppression of the gut microbiome prevents acute graft-versus-host disease following allogeneic bone marrow transplantation.
abstract: The hypothesis that elimination of facultative and strict anaerobic microorganisms from the gastro-intestinal tract by antimicrobial drugs in the period of time around allogeneic bone marrow transplantation (BMT) prevents acute graft-versus-host disease (GVHD), was examined in a cohort of 112 children grafted between 1989 and 2002 for hematological malignancies. All patients received T-cell replete marrow from human leukocyte antigens (HLA) matched sibling donors under identical transplantation conditions. To eliminate microorganisms from the gastro-intestinal tract, total gastro-intestinal decontamination (GID) was applied by high doses of non-absorbable antimicrobial drugs while the graft recipient was maintained in strict protective isolation. About half of the children (51%) proved to be successfully decontaminated, and about half (49%) unsuccessfully. One recipient got acute GVHD in the first group and 8 in the second group (p = 0.013). The degree of success of total GID was decisive for the occurrence of acute GVHD, irrespective of the presence of other risk factors such as higher age of recipient and/or donor, female donor for male recipient and carriership or reactivation of herpesviruses. Our results demonstrate that successful total GID of the graft recipient prevents moderate to severe acute GVHD. We suppose that substantial translocation of gastro-intestinal microorganisms or parts of these, functioning as microbial-associated molecular patterns (MAMP's), triggering macrophages/dendritic cells via pattern recognizing receptors (PRR's) is prohibited. As a consequence the initiation and progression of an inflammatory process leading to acute GVHD is inhibited.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jaak M
authors.initials: JM
authors.lastname: Vossen
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Harry F L
authors.initials: HF
authors.lastname: Guiot
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ann C T M
authors.initials: AC
authors.lastname: Vossen
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robbert G M
authors.initials: RG
authors.lastname: Bredius
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Wolterbeek
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hanny D J
authors.initials: HD
authors.lastname: Bakker
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands; Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Heidt
mesh_terms: D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D003141:Communicable Diseases / Q000150:complications; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006086:Graft vs Host Disease / Q000097:blood / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D008297:Male; D064307:Microbiota; D035781:Siblings; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome