An Integrated Outlook on the Metagenome and Metabolome of Intestinal Diseases

Abstract

Recently, metagenomics and metabolomics are the two most rapidly advancing "omics" technologies. Metagenomics seeks to characterize the composition of microbial communities, their operations, and their dynamically co-evolving relationships with the habitats they occupy, whereas metabolomics studies unique chemical endpoints (metabolites) that specific cellular processes leave behind. Remarkable progress in DNA sequencing and mass spectrometry technologies has enabled the comprehensive collection of information on the gut microbiome and its metabolome in order to assess the influence of the gut microbiota on host physiology on a whole-systems level. Our gut microbiota, which consists of prokaryotic cells together with its metabolites, creates a unique gut ecosystem together with the host eukaryotic cells. In this review, we will highlight the detailed relationships between gut microbiota and its metabolites on host health and the pathogenesis of various intestinal diseases such as inflammatory bowel disease and colorectal cancer. Therapeutic interventions such as probiotic and prebiotic administrations and fecal microbiota transplantations will also be discussed. We would like to promote this unique biology-wide approach of incorporating metagenome and metabolome information as we believe that this can help us understand the intricate interplay between gut microbiota and host metabolism to a greater extent. This novel integration of microbiome, metatranscriptome, and metabolome information will help us have an improved holistic understanding of the complex mammalian superorganism, thereby allowing us to gain new and unprecedented insights to providing exciting novel therapeutic approaches for optimal intestinal health.

Keywords: colorectal cancer; gut microbiota; inflammatory bowel disease; luminal metabolites; metabolomics; metagenomics.

Figure 1

Our intricate gut ecosystem include four bacterial phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria dominate the gut microbiota in mammals and these phyla have been reported to characterize the role of the host metabolism and physiology. Depending on the dietary lifestyle of the host, the gut microbiota and its metabolites such as N-nitroso compounds, ammonia, polyamine, taurine, bile acids, hydrogen sulphide, and short-chain fatty acids are highly implicated in the etiopathogenesis of metabolic diseases, intestinal diseases, and extraintestinal diseases, thereby playing a vital role in host health.

Figure 2

Dysbiosis-related inflammatory bowel diseases and colorectal cancer and relevant therapeutic interventions. Dysbiosis refers to the imbalance between the peace-keeping bacteria and the pathobionts, leading to intestinal diseases such as inflammatory bowel disease and colorectal cancer. Some bacterial metabolites can cause direct DNA damage or promote inflammation. Pathobionts also exert pro-inflammatory effects. In addition, the loss of barrier function will result in increased bacterial translocation, further driving pro-inflammatory pathways, resulting in tumorigenesis. Ingestion of probiotics and/or prebiotics and fecal microbiota transplantation have been reported to restore symbiosis.