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REVIEW article

Front. Immunol.

Sec. Microbial Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1675677

This article is part of the Research TopicHost and Microbe Immunometabolic Chat: A New Era of Organismal CommunicationView all 8 articles

Microbial Metabolites and Their Influence on the Tumor Microenvironment

Provisionally accepted
Huanglin  DuanHuanglin Duan1*Baisheng  XuBaisheng Xu1Peiyue  LuoPeiyue Luo2Tao  ChenTao Chen2Jun  ZouJun Zou3
  • 1The First People's Hospital of Xiushui, Jiujiang, China
  • 2Gannan Medical University, Ganzhou, China
  • 3Feng Cheng People's Hospital, Yichun, China

The final, formatted version of the article will be published soon.

While tumor immunotherapy has achieved remarkable progress in many hematological malignancies, its efficacy remains limited by key challenges, including the immunosuppressive microenvironment of solid tumors, metabolic abnormalities, and drug resistance. As a central mechanism underlying impaired immune function, metabolic reprogramming of immune cells has emerged as a pivotal focus for unraveling tumor immune evasion and therapeutic resistance. Advances in metagenomics have highlighted the significance of the human commensal microbiome as a 'second genome.' Microbial metabolites, whether circulating systemically or accumulating locally, serve as key messengers linking the microbiota to tumor immunometabolism. This review comprehensively examines the regulatory roles and metabolic mechanisms through which microbial metabolites—including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, and lipopolysaccharides (LPS)—modulate tumor immunity and immunotherapeutic responses via immune cell metabolism. These metabolites shape the tumor immune microenvironment and influence immunotherapeutic efficacy by reprogramming immune cell metabolic and biosynthetic pathways. This review underscores the central regulatory role of microbial metabolites as the 'second genome' in tumor immunometabolism, offering a theoretical foundation and potential targets to elucidate mechanisms of immunotherapeutic resistance and advance microbiota metabolism-based precision interventions.

Keywords: Microbial Metabolites, tumor immunity, Immunometabolism, Tumormicroenvironment, Immunotherapy

Received: 29 Jul 2025; Accepted: 04 Sep 2025.

Copyright: © 2025 Duan, Xu, Luo, Chen and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Huanglin Duan, The First People's Hospital of Xiushui, Jiujiang, China

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