Evidence map›Paper›PMID 39441941›Full record

Trial reportBlood2025

Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy.

Rishika Prasad, Abdur Rehman, Lubna Rehman, Faezeh Darbaniyan, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Eli Zamir, Sabine Schmidt, Tomo Hayase and 40 more

Erratum issued Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06218602 (Pilot Trial of Fecal Microbiota Transplantation for Lymphoma Patients Receiving Axicabtagene Ciloleucel Therapy.), which is not on this map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06218602 phase2recruitingnot on this map

Pilot Trial of Fecal Microbiota Transplantation for Lymphoma Patients Receiving Axicabtagene Ciloleucel Therapy.

TypeinterventionalSponsorM.D. Anderson Cancer CenterRan2024 to 2028Enrolled40ConditionsLymphomaArmsFecal Microbiota Transplantation, Chemotherapy, CAR-T Therapy
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Central nervous system infections caused by carbapenem-resistant klebsiella pneumoniae after CAR T-cell therapy in a patient with preexisting colonization: a case report and literature review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Pooled it
  2. Review
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  4. Article
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  6. Review
  7. Review
  8. Article
  9. Review
  10. Antibiotic therapy in febrile neutropenia in haematological patients: current considerations and future challenges.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
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  19. Article
  20. The Potential of the Gut Microbiota and Butyrate to Enhance CAR T-cell Therapy in Non-Hodgkin Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

50 authors.

Rishika PrasadDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-6875-0954
Abdur RehmanDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-3785-2007
Lubna RehmanDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-5832-6578
Faezeh DarbaniyanDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Viktoria BlumenbergDepartment of Medicine III, Ludwig Maximilian University of Munich University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.ORCID 0000-0003-1379-0876
Maria-Luisa SchubertDepartment of Hematology, Oncology, and Rheumatology, University Clinic Heidelberg, Heidelberg, Germany.ORCID 0009-0000-7853-4465
Uria MorSystems Immunology Department, Weizmann Institute of Science, Rehovot, Israel.
Eli ZamirDivision of Microbiome and Cancer, German Cancer Consortium, Heidelberg, Germany.
Sabine SchmidtDivision of Microbiome and Cancer, German Cancer Consortium, Heidelberg, Germany.
Tomo HayaseDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Chia-Chi ChangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Lauren McDanielDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0009-0005-1698-6657
Ivonne FloresDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Paolo StratiDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Ranjit NairDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Dai ChiharaDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-1153-2294
Luis E FayadDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Sairah AhmedDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-7302-8299
Swaminathan P IyerDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Michael WangDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-9748-5486
Preetesh JainDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-2735-168X
Loretta J NastoupilDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-6071-8610
Jason WestinDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-1824-2337
Reetakshi AroraDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Joel TurnerDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.ORCID 0009-0002-6081-3866
Fareed KhawajaDepartment of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX.
Ranran WuDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX.
Jennifer B DennisonDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-3067-0972
Meghan MengesDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
Melanie Hidalgo-VargasDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
Kayla ReidDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
Marco L DavilaDepartment of Stem Cell Transplantation and Cellular Therapy, Roswell Cancer Institute, Buffalo, NY.ORCID 0000-0002-6270-3065
Peter DregerDepartment of Hematology, Oncology, and Rheumatology, University Clinic Heidelberg, Heidelberg, Germany.
Felix KorellDepartment of Hematology, Oncology, and Rheumatology, University Clinic Heidelberg, Heidelberg, Germany.
Anita SchmittDepartment of Hematology, Oncology, and Rheumatology, University Clinic Heidelberg, Heidelberg, Germany.
Mark R TannerDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
Richard E ChamplinDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-4314-5037
Christopher R FlowersDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Elizabeth J ShpallDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
Samir HanashDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX.
Sattva S NeelapuDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0003-1045-4914
Michael SchmittDepartment of Hematology, Oncology, and Rheumatology, University Clinic Heidelberg, Heidelberg, Germany.
Marion SubkleweDepartment of Medicine III, Ludwig Maximilian University of Munich University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.ORCID 0000-0003-3905-0251
Johannes Francois-FahrmannDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-5088-0198
C K Stein-ThoeringerDepartment of Internal Medicine I, University Clinic Tüebingen, Tüebingen, Germany.
Eran ElinavSystems Immunology Department, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0002-5775-2110
Michael D JainDepartment of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.ORCID 0000-0002-7789-1257
Eiko HayaseDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-4824-8844
Robert R JenqDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Neeraj Y SainiDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

abstractAntibiotic (ABX)-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n = 58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery, n = 40; validation, n = 28). These findings were recapitulated in an immune-competent CAR-T mouse model, in which meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-Ts, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy. This trial was registered at www.clinicaltrials.gov as #NCT06218602.

Indexed as

Anti-Bacterial AgentsDysbiosisGastrointestinal MicrobiomeImmunotherapy, AdoptiveLymphoma, Large B-Cell, DiffuseAgedAnimalsFemaleHumansMaleMetabolomeMiceMiddle AgedAnti-Bacterial Agents

Identifiers

PMID39441941
PMCPMC12782970

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.