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Eubacterium limosum modulates tumor microenvironments and produces antitumor metabolites active against colorectal

Yao Lu1, Ruiting Lan2, Qianhua Fan1,3

  • 1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

The ISME Journal
|June 26, 2025
PubMed

Insights

Eubacterium limosum El1405 shows potential as a probiotic for colorectal cancer (CRC) prevention. It suppresses CRC cell growth in vitro and inhibits tumor growth in mice by altering gut microbiota and immune responses.

Area of Science:

  • Microbiology
  • Oncology
  • Immunology

Background:

  • Gut microbiota significantly influences colorectal cancer (CRC) development.
  • Eubacterium limosum is a potential probiotic with observed anti-CRC functions.
  • The precise mechanisms underlying E. limosum's anti-CRC effects require further elucidation.

Purpose of the Study:

  • To investigate the anti-CRC mechanisms of E. limosum strain El1405.
  • To evaluate the effects of El1405 on CRC cell behavior in vitro.
  • To assess the in vivo efficacy of El1405 and its derivatives in a mouse model of CRC.

Main Methods:

  • In vitro assays assessing CRC cell proliferation, colony formation, cell cycle, and apoptosis.
  • CT26 syngeneic mouse model treated with live El1405, inactivated El1405, culture supernatant, or indole derivatives.
  • 16S rRNA gene sequencing for microbiota analysis in tumors and intestines.
  • Analysis of immune cell populations and cytokine levels in the tumor microenvironment.
  • Metabolomic analysis of serum samples.

Main Results:

  • El1405 suppressed CRC cell proliferation by altering cell cycle distribution and inducing apoptosis in vitro.
  • In vivo, El1405 and its derivatives (ILA, IAA, L-arginine, butyrate) inhibited tumor growth.
  • El1405 modulated tumor and intestinal microbiota, reducing harmful bacteria like Enterobacter and Staphylococcus, while increasing beneficial Roseburia and Eubacterium.
  • El1405 administration enhanced anti-tumor immunity by increasing TNF-α, INF-γ, and CD8+ T cells, and decreasing immunosuppressive factors.
  • Metabolomic analysis confirmed El1405's role in producing indole derivatives (ILA, IAA) contributing to antitumor effects.

Conclusions:

  • E. limosum El1405 exhibits significant anti-CRC properties through direct effects on cancer cells and modulation of the tumor microenvironment.
  • The probiotic's efficacy is linked to its ability to alter gut microbiota composition and boost anti-tumor immunity.
  • Indole derivatives produced by El1405 play a crucial role in its observed antitumor effects.
  • E. limosum El1405 represents a promising probiotic candidate for colorectal cancer prevention strategies.
Keywords:
Eubacterium limosumcolorectal cancergut microbiotametabolitestumor microenvironment

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