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Protecting colonic mucus to mitigate acute intestinal graft-versus-host disease

保护结肠粘液减轻急性肠道移植物抗宿主病

基本信息

批准号：
10661510
负责人：
Robert Jenq
金额：
$ 80.75万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10661510
关键词：
Acute Acute Graft Versus Host Disease Acute leukemia Allogeneic Bone Marrow Transplantation Allogenic Antibiotics Azithromycin Bacteria Biological Assay Biometry Carbapenems Cells Clinical Colon Consumption Coupled Data Development Diet Monitoring Dietary intake Evaluation Feces Fermentation Fever Functional disorder Gene Expression Gnotobiotic Hematologic Neoplasms Hematological Disease Hematopoietic Neoplasms Homeostasis Immune Immune Targeting Immune system Immunologics Immunosuppression Inflammation Infusion procedures Intestinal Graft Versus Host Disease Intestines Large Intestine Life Link Lymphoma Malignant Neoplasms Mediating Melphalan Metabolic Mucins Mucolytics Mucous body substance Mus Oral Pathology Patients Play Prevalence Process Propionates Radiation therapy Retrospective Studies Risk Risk Factors Role Sampling Severity of illness Source Specimen Symptoms Technical Expertise Testing Time Tissues Toxic effect Transplant Recipients Work chemotherapy chronic leukemia clinical translation commensal bacteria conditioning dietary dietary restriction experimental study graft vs host disease gut inflammation gut microbiome hematopoietic cell transplantation immune function insight intestinal epithelium leukemia leukemia/lymphoma metabolomics microbial products microbiome microbiota mouse model novel strategies nutrition organ transplant recipient prebiotics prophylactic prospective stool sample sugar systemic inflammatory response translational potential

项目摘要

PROJECT SUMMARY/ABSTRACT For patients with hematologic malignancies such as leukemias, lymphomas and other related cancers, allogeneic hematopoietic cell transplantation (allo HCT) is a critically important therapy that can produce cures when other treatments cannot. Roughly 20,000 patients undergo allo BMT world-wide each year. A major risk of allo HCT continues to be graft-versus-host disease (GVHD), which results from the donor immune system recognizing the transplant recipient’s organs as foreign, leading to life-threatening inflammation. Developing strategies that reduce GVHD but leave global immune function intact should produce a major benefit for patients. One promising approach that we propose testing is targeting the subset of intestinal commensal bacteria that are capable of consuming and degrading mucins, which play a critical role in maintaining the intestinal epithelial barrier and immunological homeostasis. In this proposal, we present preliminary data identifying two common scenarios during the allo HCT process: 1) poor oral dietary intake due to conditioning or development of GVHD, and 2) administration of broad-spectrum antibiotics. Both of these often lead to increases in mucolytic bacteria. Further, we have identified antibiotic and metabolic strategies to suppress mucolytic bacteria activity. We will apply these insights to guide a mucus-focused evaluation of GVHD, in both mouse models and in stool biospecimens collected from allo HCT patients. We and others have identified the microbiota as a potent modulator of acute GVHD severity. This project proposes capitalizing on a mechanistic insight into how this can occur, with clear translational potential.

项目总结/文摘

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Can Consideration of the Microbiome Improve Antimicrobial Utilization and Treatment Outcomes in the Oncology Patient?

DOI：
10.1158/1078-0432.ccr-16-3173
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
0
作者：
Galloway-Peña JR;Jenq RR;Shelburne SA
通讯作者：
Shelburne SA

Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.

DOI：
10.1146/annurev-med-052918-122440
发表时间：
2020-01-27
期刊：
Annual review of medicine
影响因子：
10.5
作者：
Schwabkey ZI;Jenq RR
通讯作者：
Jenq RR

Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer.

DOI：
10.1186/s13073-021-00923-w
发表时间：
2021-06-23
期刊：
Genome medicine
影响因子：
12.3
作者：
Hayase E;Jenq RR
通讯作者：
Jenq RR

Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease.

卵形拟杆菌可缓解微生物群失调引起的肠道移植物抗宿主病。

DOI：
10.21203/rs.3.rs-2460097/v1
发表时间：
2023
期刊：
Research square
影响因子：
0
作者：
Hayase,Eiko;Hayase,Tomo;Mukherjee,Akash;Stinson,StuartC;Jamal,MohamedA;Ortega,MiriamR;Sanchez,ChristopherA;Ahmed,SairaS;Karmouch,JenniferL;Chang,Chia-Chi;Flores,IvonneI;McDaniel,LaurenK;Brown,AlexandriaN;El-Himri,Rawan
通讯作者：
El-Himri,Rawan

MiRKAT-S: a community-level test of association between the microbiota and survival times.