A new study in fruit flies, published by Cell Metabolism, shows that healthy microbiota of the microbiota help regulate our metabolism. The work reveals that innate immune pathways, better known as our first line of defense against bacterial infections, have a secondary job that is equally important. In the intestine, the digestive cells use an innate immune pathway to respond to harmful bacteria. But other intestinal cells, enteroendocrine cells, use the same pathway, known as IMD, to respond to “good” bacteria, adjusting the body’s metabolism to diet and intestinal conditions.
Researchers, thanks to previous studies, knew that bacteria living in the intestines of flies produce a short-chain fatty acid, acetate, which is essential for the lipid metabolism of flies and insulin signaling. Flies without bacteria in their intestines (and therefore, without acetate) accumulated droplets of fat in their digestive cells.
The new study again used fruit flies, which are easy to reproduce and manipulate genetically, and have cell types in their intestines very similar to humans. When examining flies with mutations in the innate IMD immune pathway, they again saw drops of fat in your intestines. Apparently, these are either caused by the loss of intestinal bacteria, the loss of Tachykinin (Tk), or the loss of the innate immune pathway, they are the equivalent of fatty liver. Its accumulation is a sign that the body can not adequately metabolize carbohydrates and fats.
Therefore, they defend that the innate immune pathway stimulates the enteroendocrine cells to produce tachykinin. In the absence of any of the bacteria or their degradation product, acetate, tachykinin is not produced. When the germ-free flies receive acetate, the innate immune pathway is reactivated and their metabolism normalizes. A specific innate immune receptor is required in the enteroendocrine cells, PGRP-LC, to receive the acetate signal.