Intestinal MicrobiOMICS to Define Health and Disease in Human and Mice

Matteo Serino, Chantal Chabo, Remy Burcelin

Abstract

Over the last five years an increasing effort has been made to understand the role of intestinal microbiota in health and disease, resulting in regarding to it as a new organ actively involved in the control of host metabolism, both in humans and mice. Amongst hundreds (up to thousand) germ species inhabiting the intestine, few of them are cultivable. Nevertheless, next-generation sequencing-based molecular technologies have been developed, allowing to overcome this problem and shed light on the way the gut microbiota undergoes dramatic changes during (patho)-physiological modifications of the host. Hence, the study of the overall gut germ genome (metagenome) and transcriptome (microbiome) has been launched. Thus, Genomics and Transcriptomics have begun to be increasingly used, opening the so called “Omics” era, including Proteomics and Metabolomics techniques as well. Taken together, the “Omics” allow the study of gut microbiota impact on whole host metabolism, resulting in the definition of new metabolic profiles (i.e. the presence of metabolites within the blood defines a metabolomic profile), others than those based on nucleic acid analyses only. Once demonstrated the involvement of gut microbiota within metabolic diseases, “Omics” analyses has allowed the identification of the obesity-induced gut microbiota imbalance, characterized by increased Firmicutes to Bacteroidetes ratio (metagenomics) and of the so called "core microbiome", focusing on the gut microbiota at a gene- rather than, solely, at a taxonomic-level. In addition, metabolomics studies revealed, for instance, the implication of gut microbiota to nonalcoholic fatty liver disease in insulin-resistant mice. Additionally, the use of germ-free (axenic) mice has made possible the microflora transfer to investigate the mechanisms through which gut microbes modulate host metabolism, albeit the molecular actors of the host-gut-microbiota interplay remain to be fully determined. Here, we report the role of “Omics” in the multiple analyses of gut microbiota-driven metabolic modifications of the host, proposing also to focus on lipopolysaccharides (LPS), the Gram negative proinflammatory molecules we already showed to be the initiators of metabolic diseases.

Keywords: Axenic-mice, gut microbiota, high-fat diet, inflammation, lipopolysaccharides, metabolic diseases, microbiome, 16S rRNA PCR, shotgun-sequencing, microbiota, Genomics and Transcriptomics, Proteomics and Metabolomics techniques, obesity-induced gut microbiota imbalance, core microbiome