Gut health depends on a stable barrier between the microbes in the gut and the wall of the intestinal tract. This requires a stable mucus barrier and tight junctions of the cells that line the gut wall. Both are enhanced by metabolites (primarily short chain fatty acids) of the fermentation of prebiotics in the diet. Without those barriers, it becomes much easier for microbial fragments to enter into the blood to cause metabolic endotoxemia. In addition, the same microbial fragments can travel directly to the brain via the vagus nerve to induce neuroinflammation. The integrity of the gut barrier can be significantly enhanced by high-dose omega-3 fatty acids and polyphenols. Conversely the integrity of the gut barrier can be disrupted by trans and saturated fatty acids.