Humans are colonized with microorganisms that have coevolved with us and which act to influence host physiology, metabolic, nervous, and immune function. In addition, microbes provide us with protection from pathogens and modify disease susceptibilities. There is extensive cross-talk between gut microbes and the host that influences all facets of the body. The type of diet eaten has a clear effect on the ability of different microbial groups to survive in the gut and altering dietary intake can significantly alter both microbial metabolism and composition. In the gut, host epithelial and immune cells can recognize and respond to various structural and secreted microbial signals. Metabolites formed are dependent both upon the types of bacteria and the substrates available.

Some of the main classes of metabolites that are found in the gut and have been shown to have a role in regulating host function include short-chain fatty acids (acetate, butyrate, propionate), bile acids, and indole and choline metabolites. Signalling between the gut and the brain can involve immunological, neural, and endocrine pathways. Bacteria in the gut can also recognize and respond to host-derived molecules including noradrenaline, some cytokines, and dopamine. A dysbiosis or altered balance of the gut microbiota has been associated with many human diseases, including inflammatory bowel disease, cancer, obesity, irritable bowel syndrome, cardiovascular disease, and autoimmune diseases. Thus, the concept that manipulation of the human gut microbiota towards a more balanced state through various means such as dietary modifications, prebiotics, probiotics, and fecal microbial transplantation may be beneficial as a therapeutic intervention for treatment of human disease has arisen. However, an individual’s response to manipulations aimed at altering the gut microbiota can be significantly influenced by host diet and luminal environment and it appears that a much more personalized approach may be necessary.  

Currently microbiome science has many significant limitations and caveats. Most importantly, association studies do not equal causation, and there is a lack of current evidence in human populations that changes in gut microbes can cause disease. Further, results reported in human studies often overlook many confounding factors, including intake of drugs, dietary compounds, or age or sex. Several technical limitations also exist with contamination and batch effects related to the low microbial biomass; bias related to sequencing methodology; and cross sampling vs longitudinal sampling. However, as a clearer understanding of the human microbiome emerges, the promises of specific gut microbes or microbial-derived metabolites as therapeutics in the maintenance of human health and treatment of disease will no doubt arise.