Protective Effect of Intestinal Blautia Against Neutropenic Fever in Allogeneic Transplant Recipients

Author:

Rashidi Armin1ORCID,Peled Jonathan U2,Ebadi Maryam1,Rehman Tauseef Ur1,Elhusseini Heba1,Marcello LeeAnn T2,Halaweish Hossam3,Kaiser Thomas3,Holtan Shernan G1,Khoruts Alexander4,Weisdorf Daniel J1,Staley Christopher35

Affiliation:

1. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA

2. Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College , New York, New York , USA

3. Department of Surgery, University of Minnesota , Minneapolis, Minnesota , USA

4. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota , Minneapolis, Minnesota , USA

5. BioTechnology Institute, University of Minnesota , St Paul, Minnesota , USA

Abstract

Abstract Background Neutropenic fever (NF) occurs in >70% of hematopoietic cell transplant (HCT) recipients, without a documented cause in most cases. Antibiotics used to prevent and treat NF disrupt the gut microbiota; these disruptions predict a higher posttransplantation mortality rate. We hypothesized that specific features in the gut microbial community may mediate the risk of NF. Methods We searched a large gut microbiota database in allogeneic HCT recipients (12 546 stool samples; 1278 patients) to find pairs with NF (cases) versus without NF (controls) on the same day relative to transplantation and with a stool sample on the previous day. A total of 179 such pairs were matched as to the underlying disease and graft source. Several other important clinical variables were similar between the groups. Results The gut microbiota of cases on the day before NF occurrence had a lower abundance of Blautia than their matched controls on the same day after transplantation, suggesting a protective role for Blautia. Microbiota network analysis did not find any differences in community structure between the groups, suggesting a single-taxon effect. To identify putative mechanisms, we searched a gut microbiome and serum metabolome database of patients with acute leukemia receiving chemotherapy and identified 139 serum samples collected within 24 hours after a stool sample from the same patient. Greater Blautia abundances predicted higher levels of next-day citrulline, a biomarker of total enterocyte mass. Conclusions These findings support a model in which Blautia protects against NF by improving intestinal health. Therapeutic restoration of Blautia may help prevent NF, thus reducing antibiotic exposures and transplantation-related deaths.

Funder

National Center for Advancing Translational Sciences

National Institutes of Health

University of Minnesota

NHLBI

National Cancer Institute

Memorial Sloan Kettering Cancer Center

Parker Institute for Cancer Immunotherapy

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Reference36 articles.

1. De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia;Rearigh;Ann Hematol,2020

2. Febrile neutropenia in allogeneic and autologous peripheral blood stem cell transplantation and conventional chemotherapy for malignancies;Celebi;Bone Marrow Transplant,2000

3. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease;Holler;Biol Blood Marrow Transplant,2014

4. Gut dysbiosis during antileukemia chemotherapy versus allogeneic hematopoietic cell transplantation;Rashidi;Cancer,2020

5. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation;Peled;N Engl J Med,2020

Cited by 9 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3