2024 World Conference on Lung Cancer (WCLC) - Posters-P3.02F.06 Multi-Omics Reveals Effects of Gut Microbiome on Tumor Immune and Metabolism in Mouse Lewis Lung Carcinoma Model

P3.02F.06 Multi-Omics Reveals Effects of Gut Microbiome on Tumor Immune and Metabolism in Mouse Lewis Lung Carcinoma Model

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This study investigates the influence of gut microbiota on the growth of lung cancer in mice, utilizing both low microbe (LM) and high microbe (HM) models. These models were developed using germ-free (GF) and specific pathogen-free (SPF) C57/BL6 mice, with all subjects inoculated with Lewis Lung Cancer (LLC) cells. By analyzing tumor and fecal samples through metagenomic, metabolomic, and single-cell transcriptomic sequencing, researchers identified key mechanisms by which gut microbiota impacts tumor metabolism and immunity.<br /><br />Key findings include a significant variance in tumor growth rates, with HM mice displaying notably faster tumor progression than LM mice. This growth discrepancy is linked to differences in gut microbiota diversity, specifically the beta-diversity between HM and LM mice. The study highlights that tumor volume correlates with the alpha-diversity of the gut microbiota but not with intratumoral microbiota diversity.<br /><br />Mechanistically, the gut microbiota influenced tumor glycolysis and glycine, serine, and threonine metabolism, independent of the intratumoral microbiota or host tumor cells. Certain bacterial species, such as *Sphingomonas aquatilis*, were found to promote glycolysis and amino acid metabolism in tumors, whereas species like *Mailhella sp003512875* inhibited these processes.<br /><br />Single-cell transcriptomic sequencing revealed that tumor functions like vasculogenesis and morphogenesis, as well as tissue remodeling and DNA repair capabilities of cancer-associated cells, were elevated in LM tumors. The study also found a reduction in the number and antitumor activity of CD8 T cells, macrophages, and M1-type macrophage polarization in HM tumors.<br /><br />The research underscores the complex interplay between gut microbiota, tumor metabolism, and immune environment, suggesting that gut-derived metabolites could potentially enhance or suppress antitumor immunity, though further investigations are required.

Asset Subtitle

Zixuan Hu

Meta Tag

Speaker Zixuan Hu

Topic Tumor Biology – Preclinical Biology

Keywords

gut microbiota

lung cancer

mice models

tumor metabolism

immune environment

microbiota diversity

metagenomic sequencing

metabolomic analysis

single-cell transcriptomics

antitumor immunity