GUT MICROBIOME AND ITS ROLE IN INFLAMMATORY DISEASES: A BIOMEDICAL SYSTEMS APPROACH

Abstract

The gut microbiome—an ecosystem of bacteria, archaea, viruses, and fungi that inhabit the gastrointestinal tract—plays a central role in human physiology and immunity. Dysbiosis or disruption of this ecosystem and its state has been discovered to play a role in a continuum of inflammatory disease including inflammatory bowel disease or rheumatoid arthritis and systemic inflammatory diseases. The article adopts a biomedical systems perspective because it is aimed at generalizing existing mechanistic information, multi-omics and network-based techniques to methodologies, and proposing an analytical model that can transform microbiome signatures into diagnostic, prognostic and therapeutic services. The paper employs an experimental design that is reproducible and involves shotgun metagenomics, meta transcriptomics, fecal and serum metabolomics, host transcriptomics and immunophenotyping in its analysis, which is network inferred using machine learning as well as patient stratified. As the simulations and representative results therein reveal, there are some trends: taxonomic diversity declines and fatty acid-producing taxa of short chains, bile acid metabolism, and a new taxonomic structure of micro-scale clusters are observed, which is linked to host immune activation. The discussion puts these findings into perspective to inform about the aspects of causality issues, confounders (diet, medication, environment), and barriers to clinical microbiome translationally. It concludes that this will cause the synthesis of mechanistic microbiology with systems level information and serious causal inference to the transition between association and action in inflammatory ailment.