Lung microbiome in lung cancer: A new horizon in cancer study.

Lung cancer (LC) is the second most prevalent cancer worldwide and a leading cause of cancer-related deaths. Recent technological advancements have revealed that the lung microbiome, previously thought to be sterile, is host to various microorganisms. The association between the lung microbiome and LC initiation, progression, and metastasis is complex and contradictory. However, disruption in the homeostasis of microbiome compositions correlated with the increased risk of LC. This review summarises current knowledge on the most recent developments and trends in lung cancer-related microbiota or microbial components. This manuscript aims to provide information on this rapidly evolving field while giving context to the general role of the lung microbiome in LC. In addition, this review briefly discussed the causative association of lung microbiome with LC. We will review the mechanisms of how lung microbiota influences carcinogenesis, focusing on microbiota dysbiosis. Moreover, we will also discuss the host-microbiome interaction as host-microbiota plays a crucial role in stimulating and regulating the immune response. Finally, we provide information on the diagnostic role of the microbiome in LC. It aims to offer an overview of the lung microbiome as a predictive and diagnostic biomarker in LC.

The colibactin-producing Escherichia coli alters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance.

Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8+ T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land's cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5∆ClbQ). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.