Undigested Food and Gut Microbiota May Cooperate in the Pathogenesis of Neuroinflammatory Diseases: A Matter of Barriers and a Proposal on the Origin of Organ Specificity

As food is an active subject and may have anti-inflammatory or pro-inflammatory effects, dietary habits may modulate the low-grade neuroinflammation associated with chronic neurodegenerative diseases. Food is living matter different from us, but made of our own nature. Therefore, it is at the same time foreign to us (non-self), if not yet digested, and like us (self), after its complete digestion. To avoid the efflux of undigested food from the lumen, the intestinal barrier must remain intact. What and how much we eat shape the composition of gut microbiota. Gut dysbiosis, as a consequence of Western diets, leads to intestinal inflammation and a leaky intestinal barrier. The efflux of undigested food, microbes, endotoxins, as well as immune-competent cells and molecules, causes chronic systemic inflammation. Opening of the blood-brain barrier may trigger microglia and astrocytes and set up neuroinflammation. We suggest that what determines the organ specificity of the autoimmune-inflammatory process may depend on food antigens resembling proteins of the organ being attacked. This applies to the brain and neuroinflammatory diseases, as to other organs and other diseases, including cancer. Understanding the cooperation between microbiota and undigested food in inflammatory diseases may clarify organ specificity, allow the setting up of adequate experimental models of disease and develop targeted dietary interventions.