Dysbiosis of the gut microbiota in disease

There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of bothintestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritablebowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolicsyndrome, cardiovascular disease, and obesity.In many of these conditions, the mechanisms leading to disease development involve the pivotal mutualisticrelationship between the colonic microbiota, their metabolic products, and the host immune system. Theestablishment of a ‘healthy’ relationship early in life appears to be critical to maintaining intestinal homeostasis.Whilst we do not yet have a clear understanding of what constitutes a ‘healthy’ colonic microbiota, a picture isemerging from many recent studies identifying particular bacterial species associated with a healthy microbiota. Inparticular, the bacterial species residing within the mucus layer of the colon, either through direct contact with hostcells, or through indirect communication via bacterial metabolites, may influence whether host cellular homeostasisis maintained or whether inflammatory mechanisms are triggered. In addition to inflammation, there is someevidence that perturbations in the gut microbiota is involved with the development of colorectal cancer. In this case,dysbiosis may not be the most important factor, rather the products of interaction between diet and themicrobiome. High-protein diets are thought to result in the production of carcinogenic metabolites from thecolonic microbiota that may result in the induction of neoplasia in the colonic epithelium.Ever more sensitive metabolomics methodologies reveal a suite of small molecules produced in the microbiomewhich mimic or act as neurosignallers or neurotransmitters. Coupled with evidence that probiotic interventionsmay alter psychological endpoints in both humans and in rodent models, these data suggest that CNS-relatedco-morbidities frequently associated with GI disease may originate in the intestine as a result of microbial dysbiosis.This review outlines the current evidence showing the extent to which the gut microbiota contributes tothe development of disease. Based on evidence to date, we can assess the potential to positively modulate thecomposition of the colonic microbiota and ameliorate disease activity through bacterial intervention