Doki Noriko, Suyama Masahiro, Sasajima Satoshi, Ota Junko, Igarashi Aiko, Mimura Iyo, Morita Hidetoshi, Fujioka Yuki, Sugiyama Daisuke, Nishikawa Hiroyoshi, Shimazu Yutaka, Suda Wataru, Takeshita Kozue, Atarashi Koji, Hattori Masahira, Sato Eiichi, Watakabe-Inamoto Kyoko, Yoshioka Kosuke, Najima Yuho, Kobayashi Takeshi, Kakihana Kazuhiko, Takahashi Naoto, Sakamaki Hisashi, Honda Kenya, Ohashi Kazuteru
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Ann Hematol. 2017 Sep;96(9):1517-1523. doi: 10.1007/s00277-017-3069-8. Epub 2017 Jul 21.
Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.
异基因造血干细胞移植(allo-HSCT)后,胃肠道的移植后微生物多样性与临床结局密切相关。然而,关于allo-HSCT前粪便微生物群的影响知之甚少。我们分析了2013年至2015年间107例allo-HSCT受者在预处理前约2周的粪便样本。使用16S rRNA基因测序进行微生物分析。通过计算香农指数估计基于操作分类单元的微生物多样性。根据多样性指数将患者分为三组:低(<2)、中(2, 3)和高(>3)多样性(分别为18例(16.8%)、48例(44.9%)和41例(38.3%)患者)。三组在20个月总生存率、复发累积发生率和非复发死亡率方面无显著差异。三组中II至IV级急性移植物抗宿主病(aGVHD)的累积发生率相似(第100天时,低多样性组为55.6%;中多样性组为35.4%;高多样性组为48.8%,p = 0.339)。此外,我们发现三组中II至IV级急性胃肠道GVHD的累积发生率无差异(第100天时,低多样性组为38.9%;中多样性组为21.3%;高多样性组为24.4%,p = 0.778)。关于allo-HSCT前微生物群的组成,aGVHD患者的厚壁菌门丰度显著高于非aGVHD患者(p < 0.01)而拟杆菌门丰度呈较低趋势(p = 0.106)。在整个allo-HSCT过程中维持拟杆菌门可能是预防aGVHD的一种策略