Microbiome-Mediated Immune Signaling in Inflammatory Bowel Disease and Colorectal Cancer: Support From Meta-omics Data

Abstract

Chronic intestinal inflammation and microbial dysbiosis are hallmarks of colorectal cancer (CRC) and inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis. However, the mechanistic relationship between gut dysbiosis and disease has not yet been fully characterized. Although the "trigger" of intestinal inflammation remains unknown, a wealth of evidence supports the role of the gut microbiome as a mutualistic pseudo-organ that significantly influences intestinal homeostasis and is capable of regulating host immunity. In recent years, culture-independent methods for assessing microbial communities as a whole (termed meta-omics) have grown beyond taxonomic identification and genome characterization (metagenomics) into new fields of research that collectively expand our knowledge of microbiomes. Metatranscriptomics, metaproteomics, and metabolomics are meta-omics techniques that aim to describe and quantify the functional activity of the gut microbiome. Uncovering microbial metabolic contributions in the context of IBD and CRC using these approaches provides insight into how the metabolic microenvironment of the GI tract shapes microbial community structure and how the microbiome, in turn, influences the surrounding ecosystem. Immunological studies in germ-free and wild-type mice have described several host-microbiome interactions that may play a role in autoinflammation. Chronic colitis is a precursor to CRC, and changes in the gut microbiome may be an important link triggering the neoplastic process in chronic colitis. In this review, we describe several microbiome-mediated mechanisms of host immune signaling, such as short-chain fatty acid (SCFA) and bile acid metabolism, inflammasome activation, and cytokine regulation in the context of IBD and CRC, and discuss the supporting role for these mechanisms by meta-omics data.

Keywords: colorectal cancer; gut microbiome; inflammatory bowel diesases; metabolomics; metagenomics; metaproteomics.