Interaction Between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

Abstract

BackgroundAlthough variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNAs expression in human CRC tumor and normal tissues and the microbiome composition associated with these same tissues.MethodWe sequenced the small RNAs from patient-matched tumor and normal tissue samples collected from 44 human CRC patients performed an integrated analysis with microbiome taxonomic composition data from these same samples. We then interrogated the functions of the bacteria correlated with miRNAs that were differentially expressed (DE) between tumor and matched normal tissues, as well as the functions of miRNAs correlated with bacterial taxa that have been previously associated with CRC, including Fusobacterium, Providencia, Bacteroides, Akkermansia, Roseburia, Porphyromonas, and Peptostreptococcus.ResultsWe identified 76 miRNAs as DE between CRC and normal tissue, including known oncogenic miRNAs miR-182, miR-503, and miR-17∼92. These DE miRNAs were correlated with the relative abundance of several bacterial taxa, including Firmicutes, Bacteroidetes, and Proteobacteria. Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions, and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa.ConclusionsOur work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. Our results support a role for miRNAs in mediating a bi-directional host-microbiome interaction in CRC. In addition, we highlight sets of potentially interacting microbes and host miRNAs, suggesting several pathways that can be targeted via future therapies.

Probiotics and MicroRNA: Their Roles in the Host–Microbe Interactions

“…In addition to participating in the regulation of intestinal function, the close relationship between miRNAs and gut microbiota has also been confirmed ( Masotti, 2012 ; Belcheva, 2017 ; Hoban et al, 2017 ; Yuan et al, 2018 ). A potential mechanism by which gut microbiota affect host physiology is to modulate host gene expression through miRNAs.…”

“…Actually, a bidirectional relationship exists between gut microbiome and miRNAs. An analysis of miRNA sequencing in human CRC tumor and normal tissues identified 76 differentially expressed miRNAs that are correlated with the abundance of microbes in the tumor microenvironment, including Firmicutes, Bacteroidetes, and Proteobacteria ( Yuan et al, 2018 ). Moloney et al (2018) proved that the expression of murine miRNAs produced by IECs in feces was influenced by the gut microbiota ( Gu et al, 2017 ).…”

“…They discovered that the relative abundance of the phyla Bacteroidetes and Firmicutes was significantly correlated with the level of miR-141-3p and phyla Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, and Proteobacteria were significantly correlated with the level of miR-200a-3p. As a valuable tool, host miRNAs play significant roles in maintaining intestinal homeostasis ( Link et al, 2010 ; Moloney et al, 2018 ; Yuan et al, 2018 ). Recent studies have illustrated the mechanism by which the host could foster favorable microbiota via fecal miRNA ( Liu et al, 2016 ; Jiayi et al, 2019 ).…”

Overview of host miRNA properties and their association with epigenetics, long non-coding RNAs, and Xeno-infectious factors

“…According to the association between miRNAs and microbes involved in the pathogenesis of the disease, there is some gut microbiota such as Proteobacteria, Bacteroidetes, and Firmicutes that correlate with colorectal cancer (CRC) by inducing some oncogenic miRNAs such as miR-503, miR-182and mir-17 ~ 92 cluster [ 199 ]. In this regard, Zhou et al reported that tumor suppressor miR-203, which targets CASK oncogene, can be downregulated by Helicobacter pylori infection and promoted the proliferation and invasion of gastric cancer [ 200 ].…”

Gut Microbiota Diversity in Lean Athletes Is Associated with Positive Energy Balance

“…Gut microbiota is involved in the regulation of many physiological processes through interactions with the host, such as nutrient uptake and metabolism [3], food digestion [4], synthesis of bile acids [5], and regulation of host gene expression [6]. However, one of the other metabolic roles of gut microbiota is to harvest energy from the host diet.…”