Microglia play a vital role maintaining brain homeostasis but can also cause persistent neuroinflammation. Short-chain fatty acids (SCFAs) produced by the intestinal microbiota have been suggested to regulate microglia inflammation indirectly by signaling through the gut-brain axis or directly by reaching the brain. The present work evaluated the anti-inflammatory effects of SCFAs on lipopolysaccharide (LPS)-stimulated microglia from mice fed inulin, a soluble fiber that is fermented by intestinal microbiota to produce SCFAs in vivo, and SCFAs applied to primary microglia in vitro.
Reviews how acetate, propionate and butyrate, made by gut bacteria fermenting dietary fibre, act on the gut lining, the immune and endocrine systems and the vagus nerve, and the evidence that they reach the brain and act there directly.
Microglia in germ-free mice were immature and responded poorly to infection. Recolonizing the mice with a complex microbiota restored them, and short-chain fatty acids alone, given in drinking water, were enough to restore microglial maturation. Mice lacking the receptor FFAR2 showed similar microglial defects.