Gastrointestinal Inflammation and the Gut Microbiome: An Evolving Conceptual Framework with Implications for Diagnosis and Therapy in Inflammatory Bowel Disorders

Abstract

The human gut microbiome has garnered much attention over the past two decades with important discoveries linking it to human health and disease. The commensal bacterial flora evolves due to the influence of a number of factors including diet, pathogen exposure, environmental toxicants, disease states, and a challenged microenvironment that requires balancing with the host itself. However, the composition of bacterial species can impact and contribute to the development of local and systemic inflammation. Among the factors attributed to intestinal inflammation are dysbiosis caused by pathogenic bacteria, following decreased host immunity or loss of intestinal barrier function. Dysbiosis can also be triggered by antibiotic therapy or the use of other medications that allow for colonisation of pathogenic bacteria, such as proton pump inhibitors. The imbalance with commensal bacteria leads to the generation of proinflammatory mediators and a reduction of host immune defences, due to a lack of short-chain fatty acid generation needed for energy production to maintain barrier and immune function. The initially localised inflammation results in further dysbiosis as former commensal bacteria are able to breach the barrier and cause systemic immune responses. Low-grade systemic inflammation is a hallmark of inflammatory bowel disease. Because a specific dysbiosis is common in patients with inflammatory bowel disease, it can serve as an early diagnostic marker in its development. Furthermore, faecal microbiome transplants have shown promising benefits in patients with ulcerative colitis and Crohn’s disease.