Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity

Blood Advances - Tập 4 Số 9 - Trang 1824-1832 - 2020
Mathilde Payen1,2, Ioannis Nicolis3, Marie Robin4, David Michonneau4,5, Johanne Delannoy1, Muriel Thomas6, Nathalie Kapel1,7, Béatrice Berçot2, Marie‐José Butel1, Jérôme Le Goff5,2, Gèrard Socié4,5, Clotilde Rousseau1,2
1INSERM U1139, Faculté de Pharmacie, Université de Paris, Paris, France;
2Laboratoire de Microbiologie, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;
3EA7537 Biostatistique, Modélisation et Traitement des Données Biologiques, Faculté de Pharmacie, Université de Paris, Paris, France;
4Hematology / Transplantation, Hôpital Saint-Louis AP-HP, PARIS, France
5Inserm U976, Université de Paris, Paris, France
6UMR1319, Micalis Institute, Institut National de la Recherche Agronomique, Jouy-en-Josas, France; and
7Laboratoire de Coprologie Fonctionnelle, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France

Tóm tắt

AbstractAcute graft-versus-host disease (aGVHD) is the main complication of hematopoietic stem cell transplantation (HSCT). Changes in gut microbiota composition have been associated with subsequent aGVHD, and reconstitution of healthy microbiota is currently being explored as a therapeutic approach. However, the specific actors in the intestinal ecosystem involved in the pathologic process at the time of aGVHD onset are not yet fully known. We prospectively collected stool samples from patients who underwent allogeneic HSCT. Patients sampled at aGVHD onset were compared with non-GVHD patients. To identify phylogenetic and functional signatures of the disease process, we determined fecal short-chain fatty acid (SFCA) profiles and used high-throughput DNA sequencing and real-time quantitative polymerase chain reaction to assess the microbiota composition. Microbiota alterations were highly specific of gastrointestinal (GI) aGVHD severity. Bacterial biomass and α-diversity were lower in severe aGVHD. We identified several bacterial signatures associated with severe aGVHD at disease onset; a negative correlation was observed with anaerobic bacteria of the Lachnospiraceae, especially the Blautia genus, and Ruminococcaceae families. In parallel, in severe aGVHD patients, we showed a dramatic decrease in the levels of the main SFCAs: acetate (75.8%), propionate (95.8%), and butyrate (94.6%). Mild aGVHD patients were characterized by conserved levels of propionate and Blautia propionate producers. Butyrate was significantly decreased in all GI aGVHD stages, representing a potential diagnostic marker of the disease. Specific microbiota and metabolic alterations were thus associated with aGVHD severity and may be useful for diagnostic and pathophysiologic purposes.

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Blood Advances

Tập 4 Số 9

1824-1832

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