# Influence of stage-specific and location-related intratumoral microbiota on prognosis and metabolic reprogramming in non-small cell lung cancer

**Authors:** Yuwei Zhao, Zhuang Tong, Lin Liu, Rongjie Yang, Zhongfeng Chen, Zheng Wang

PMC · DOI: 10.3389/fimmu.2025.1675448 · Frontiers in Immunology · 2026-01-05

## TL;DR

This study explores how the microbiota inside non-small cell lung cancer tumors varies by stage and location, and how it affects prognosis and metabolism.

## Contribution

The study reveals stage- and location-specific microbial patterns in NSCLC and identifies Bacteroides as a potential therapeutic target.

## Key findings

- Microbial composition differs significantly between early and advanced NSCLC stages and between upper and lower lung lobes.
- Bacteroides is enriched in early-stage tumors and is associated with improved patient prognosis.
- Bacteroides suppresses tumor cell proliferation and migration while promoting apoptosis through immune microenvironment remodeling.

## Abstract

Mounting evidence links intratumoral microbiota to tumor progression and immune regulation, but stage-specific and location-related microbial characteristics in NSCLC remain insufficiently explored.

Tumor and adjacent non-tumor tissues from 21 NSCLC patients were analyzed using 16S rRNA gene sequencing to profile the intratumoral microbiota. Functional pathway analysis, in vitro co-culture experiments (A549/HCC827 cells), and in vivo mouse models were employed to validate microbial functions.

Microbial composition exhibited significant heterogeneity by tumor stage (early vs. advanced) and anatomical location (upper vs. lower lobes). Bacteroides was identified as a key genus enriched in early-stage tumors and correlated with improved prognosis. Functional analysis revealed enrichment of tumor-associated microbiota in metabolic and biosynthetic pathways (e.g., carbon metabolism, amino acid biosynthesis). Further experiments demonstrated that Bacteroides significantly suppressed NSCLC cell proliferation, inhibited migration, and promoted apoptosis, with anti-tumor effects mediated by remodeling the tumor immune microenvironment.

These findings elucidate intricate associations between intratumoral microbiota, immune cell infiltration, and patient prognosis, highlighting Bacteroides as a potential prognostic biomarker and therapeutic target for NSCLC

## Linked entities

- **Diseases:** non-small cell lung cancer (MONDO:0005233), NSCLC (MONDO:0005233)
- **Species:** Bacteroides (taxon 816)

## Full-text entities

- **Diseases:** non-small cell lung cancer (MESH:D002289), Tumor (MESH:D009369)
- **Chemicals:** carbon (MESH:D002244), amino acid (MESH:D000596)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Bacteroides (genus) [taxon 816], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12813048/full.md

## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12813048/full.md

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Source: https://tomesphere.com/paper/PMC12813048