Recent research has found an association between colorectal cancer (CRC) and variations in the gut microbiome composition. Although mice research supports the theory that tumor development appears to be driven by interactions between the gut microbiome and host genomics, mechanisms involved in the crosstalk between colorectal carcinogenesis and the gut microbiome are still unknown.
A new study, led by Prof. Ran Blekhman from the University of Minnesota (USA), has found that microbes associated with colorectal cancer correlate with microribonucleic acids that regulate mucin biosynthesis, which in turn may recruit pathogens to tumors.
The researchers studied the association between microribonucleic acids (miRNAs) expression—which are small non-coding RNAs that can shape the composition of the gut microbiome and which may regulate CRC progression by controlling diverse cellular functions—and gut microbiome composition in a total of 88 matched tumor and adjacent normal tissues from 44 patients.
Seventy-six miRNAs have been identified as differentially expressed in tissue from CRC tumors and normal tissue, which included the oncogenic miRNAs miR-182, miR-503 and mir-17~92 cluster. These, in turn, regulate multiple tumor-suppressive genes in CRC and contribute to the malignant transformation of colon adenoma to adenocarcinoma and malignant progression of CRC. These differentially expressed miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes, Bacteroidetes and Proteobacteria.
Meanwhile, bacteria correlated with differentially expressed miRNAs showed functional differences between tumor and normal tissues. Specifically, there was an enrichment in pathways related to transporters, peptidoglycan and terpenoid backbone biosynthesis. In contrast, the uncorrelated bacteria showed increased signaling and metabolic pathways, from signal transduction to amino acid metabolism, energy metabolism and linoleic acid metabolism. These results show that bacteria correlated with differentially expressed miRNAs were enriched with distinct predicted metabolic categories, although a causal relationship cannot be inferred.
The researchers also focused on bacterial genera previously associated with CRC in order to explore whether miRNAs correlated with CRC-associated bacteria show an enrichment in cancer-related genes and pathways. Akkermansia correlated with miRNAs associated with the CRC pathway, whereas Fusobacterium, Providencia and Roseburia correlated with miRNAs associated with other cancer type pathways. One of the main findings was that CRC-associated bacteria were correlated with miRNAs that regulate genes related to interactions with microbes. For instance, these miRNAs were involved in regulating glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor.
To sum up, this is the first study that characterizes relationships between gut microbial communities and miRNA expression in human CRC tissues. Experimental validations are needed to investigate the correlations and their functional implications. According to the authors “Our data show a highly interconnected correlation network between miRNA expression and the composition of the microbiome and support the role for miRNAs in mediating host-microbiome interactions. Follow-up studies using model systems are warranted to assess the causal role of individual microbes and miRNAs in CRC.”
Yuan C, Burns MB, Subramanian S, et al. Interaction between host microRNAs and the gut microbiota in colorectal cancer. mSystems. 2018; 3(3):e00205-17. doi: 10.1128/mSystems.00205-17.