Jenq, R.R. et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J. Exp. Med. 209, 903-911

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Journal of Experimental Medicine (Impact Factor: 12.52). 04/2012; 209(5):903-11. DOI: 10.1084/jem.20112408
Source: PubMed


Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.


Available from: Raya Khanin
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    • "Hence, we now know that there are three different enterotypes (Arumugam et al, 2011) and that dysbiosis has important impact on auto-immunity, allergy and auto-inflammatory diseases. There are also strong indications that the microbiota varies amongst patients with cancer and has an impact on the occurrence of MBI and the related inflammatory response (Manichanh et al, 2008; Jenq et al, 2012). Moreover, oral and colonization with Candida species have been related to the occurrence of GVHD, especially of the gut (van der Velden et al, 2013). "
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    • "Another study showed a marked expansion of Lactobacillales in murine GVHD. Elimination of this species from the flora of mice before allo-HSCT aggravated GVHD, whereas its reintroduction mediated significant protection, indicating that the microbiota can modulate the severity of intestinal inflammation (18). A recent study suggested that not only bacteria but also host fungal communities (mycobiome) can critically shape acute GVHD (19). "
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    • "These include the human commensal bacteria Bacteroides fragilis (Round and Mazmanian, 2010), Faecalibacterium prausnitzii (Sokol et al. 2008), several Lactobacillus spp. (Jenq et al. 2012; Shimazu et al. 2012; van Baarlen et al. 2013) and Bifidobacterium spp. (Imaoka et al. 2008; Khokhlova et al. 2012). "
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