“You are not what you think you are. Instead of the form staring back at you when you look in the mirror, what you should imagine is your body as a collection of multiple dynamic ecosystems made up of very tiny, and very biologically diverse, organisms.” – Rob DeSalle
The human intestinal microbiome acts as a signaling hub that integrates environmental inputs, such as diet and lifestyle, with our genetic and metabolic pathways. Its impacts are widespread across host systems, including the immune system,1 which is capable of adapting and responding to a wide range of challenges. How does the microbiome interact with the immune system, and how do these interactions help determine a state of health or disease in the body?
Reciprocal cross-talk between the microbiome and cells in the intestinal mucosal immune system is well-documented.1 We now understand that this cross-talk is important for immune system maturation and modulation across all developmental stages;2 studies of germ-free mice demonstrate that a lack of gut microbiota leads to significant immune deficiency.3,4 Maintaining a homeostatic balance between microbial activity and host immune response toward the microbiota is what allows the immune system to function appropriately to defend against infection yet also demonstrate appropriate tolerance.5
Commensal microbes are symbiotic species, playing a key role in immune homeostasis. Commensal bacteria produce metabolites such as short-chain fatty acids (SCFAs) and amino acid derivatives that enhance the gut barrier integrity, promote immune-balancing T regulatory (Treg) cell formation, and modulate the production of proinflammatory mediators.2-4 Species such as Bacteroides fragilis produce polysaccharides with anti-inflammatory effects—specifically the inhibition of interleukin 17 (IL-17) and enhanced activity of Treg cells.3
Conversely, an imbalance between commensal and pathogenic species, known as dysbiosis, activates pathogenic mechanisms. Pathogen activation of toll-like receptors (TLRs), found on intestinal immune cells, creates proinflammatory innate and adaptive immune responses, including Th17 differentiation and recruitment of neutrophils and macrophages to the affected site.1,5,6 These effects can be both acute and chronic, if dysbiosis persists. In patients with inflammatory bowel disease, intestinal dysbiosis triggers an abnormal adaptive immune response that increases the pathological inflammatory processes of the disease and destruction of the gastrointestinal tract.3 Intestinal microbial composition is also implicated in the onset of celiac disease in individuals who carry the susceptible HLA haplotypes.4
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