Prolonged gut microbial alterations in post-transplant survivors of allogeneic haematopoietic stem cell transplantation

被引:11
作者
Hino, Akihisa [1 ]
Fukushima, Kentaro [1 ,8 ]
Kusakabe, Shinsuke [1 ]
Ueda, Tomoaki [1 ]
Sudo, Takao [1 ,2 ]
Fujita, Jiro [1 ]
Motooka, Daisuke [2 ,3 ]
Takeda, Aya K. K. [4 ]
Shinozaki, Natsuko O. O. [4 ]
Watanabe, Satoshi [4 ]
Yokota, Takafumi [1 ,5 ]
Shibayama, Hirohiko [1 ,6 ]
Nakamura, Shota [2 ,3 ,9 ]
Hosen, Naoki [1 ,2 ,7 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Hematol & Oncol, Suita, Japan
[2] Osaka Univ, Inst Open & Transdisciplinary Res Initiat OTRI, Integrated Frontier Res Med Sci Div, Suita, Japan
[3] Osaka Univ, Res Inst Microbial Dis, Dept Infect Metagen, Suita, Japan
[4] Cykinso Inc, Tokyo, Japan
[5] Osaka Int Canc Inst, Dept Hematol, Osaka, Japan
[6] Natl Hosp Org, Osaka Natl Hosp, Dept Hematol, Osaka, Japan
[7] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Lab Cellular Immunotherapy, Suita, Japan
[8] Osaka Univ, Grad Sch Med, Dept Hematol & Oncol, Suita, Osaka 5650871, Japan
[9] Osaka Univ, Res Inst Microbial Dis, Dept Infect Metagen, Suita, Osaka 5650871, Japan
基金
日本学术振兴会;
关键词
aGVHD; allogeneic haematopoietic stem cell transplantation; cGVHD; gut microbiota; second cancer; VERSUS-HOST-DISEASE; CHRONIC GRAFT; SOLID CANCERS; DIVERSITY; BUTYRATE; RISK;
D O I
10.1111/bjh.18574
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Dysbiosis of the gut microbiota has been reported to increase early complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, it remains unclear whether gut microbial alterations persist during late complications, such as chronic graft-versus-host disease (cGVHD) or secondary cancers. Here, we analysed the gut microbiota of 59 patients who survived for 1-21.7 years (median, 6.4 years) after allo-HSCT. Long-term survivors showed lower gut microbial diversity than the age- and sex-matched healthy controls. This decreased diversity was reflected in the reduced abundance of the butyrate-producing bacteria. Patients with a history of grade 3 acute graft-versus-host disease (aGVHD) exhibited higher Veillonella abundance than patients with a history of grade 1-2 or non-aGVHD cases. The abundance of Faecalibacterium showed no decrease only in limited cGVHD cases. Additionally, the microbial structure in the secondary cancer group was significantly different (p < 0.05) from that in the non-secondary cancer group. This study is the first to show that microbial dysbiosis is present over a 10-year lifetime after discharge following allo-HSCT. Our results suggest that these prolonged gut microbial alterations may be associated with the development and exacerbation of late complications in post-transplant survivors.
引用
收藏
页码:725 / 737
页数:13
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