Microbiomes, Their Function, and Cancer: How Metatranscriptomics Can Close the Knowledge Gap

Abstract

The interaction between the microbial communities in the human body and the onset and progression of cancer has not been investigated until recently. The vast majority of the metagenomics research in this area has concentrated on the composition of microbiomes, attempting to link the overabundance or depletion of certain microorganisms to cancer proliferation, metastatic behaviour, and its resistance to therapies. However, studies elucidating the functional implications of the microbiome activity in cancer patients are still scarce; in particular, there is an overwhelming lack of studies assessing such implications directly, through analysis of the transcriptome of the bacterial community. This review summarises the contributions of metagenomics and metatranscriptomics to the knowledge of the microbial environment associated with several cancers; most importantly, it highlights all the advantages that metatranscriptomics has over metagenomics and suggests how such an approach can be leveraged to advance the knowledge of the cancer bacterial environment.

Current progresses and challenges for microbiome research in human health: a perspective

“…Meta-transcriptomics can be performed via short- or long- read sequencing of mRNA, usually after filtering out highly abundant ribosomal rRNA, whereas both meta-proteomics and metabolomics data are generated via mass spectrometry. Specifically, meta-transcriptomics can provide insights into the microbial genetic pathways, by quantifying the abundance of transcripts in a sample reflecting bacterial gene expression activity ( Aitmanaitė et al., 2023 ); Meta-proteomics is complementary to metagenomics and meta-transcriptomic since it reflects the activity of cellular translational and post-translational processes, by measuring the levels of all the proteins synthesized by the microbiota and the host, and, hence, providing insights into the functional role of microorganisms in host health ( Hardouin et al., 2021 ); Metabolomics allow researchers to acquire a better understanding of metabolic and biochemical processes involving the microbiota and the host, by determining the levels of all small molecules in the microenvironment ( Bartsch et al., 2023 ). An interesting application of multi-omics is described in a study on the dopamine metabolism in the marine yeast Meyerozyma guilliermondii GXDK6, by using WGS for identifying the key genes for dopamine biosynthesis, and transcriptomics as well as proteomics for showing the level of activation of the related metabolic pathway ( Sun et al., 2024 ).…”

Gut Metatranscriptomics Based De Novo Assembly Reveals Microbial Signatures Predicting Immunotherapy outcomes in Non-Small Cell Lung Cancer

“…In addition, it was reported in patients with oral squamous cell carcinoma (OSCC) evaluated by MTR analysis, that an increase in peptidase activity, oxidative stress, and iron acquisition is overrepresented in tumor samples compared to healthy tissues [19]. The pathway analysis shed light on the upregulation of anaerobic respiration, ribosome biogenesis, and glycerophospholipid metabolism, and the downregulation of inositol phosphate and flavonoid metabolism in breast cancer [13]. A study by Wong-Rolle et al [20] examined the mutational burden of the tumor and the adjacent tissue.…”

“…The widespread joint -use of the -omics technologies allows us to observe an extensive molecular landscape and behavior of a particular microbe, or the community level. The characterization of the bacterial taxa can be performed with DNA-based shotgun metagenomics (MG), RNA-based metatranscriptomics (MTR), and protein-based metaproteomics methods [13]. Most studies used so far MG approaches that provides information on the relative abundance and metabolic potential of certain taxonomic units, meanwhile the MTR that brings us data referring to the gene expression profile of the microbial community with a focus on currently active genes [14].…”

Biofilms and core pathogens shape the tumor microenvironment and immune phenotype in colorectal cancer

“… 16 Recently, metatranscriptomic studies of both the host and bacteria (dual-RNAseq) have investigated the bacteria and host interplay in some infectious diseases, 17 , 18 but only few metatranscriptomic studies in CRC exist. 19 , 20 …”