There is no doubt that gut bacteria have become one of the most important focuses of biological and medical research. Over the years, we have learned that the different populations of bacteria that inhabit the gut often have significant effects on various functions of the body, including the immune system.
The different populations of gut bacteria exist in virtually all animals under a certain functional balance. When this balance is disrupted—for example, because of disease or medication—it gives rise to a condition called commensal dysbiosis that is associated with a number of pathologies and even a decreased lifespan. Despite this knowledge, little is known as to how exactly the gut bacteria affect general health and vice versa. In a paper published today in Immunity, scientists from École polytechnique fédérale de Lausanne present a mechanism by which problems of the immune system can cause commensal dysbiosis, which, in turn, promotes age-related pathologies.
Using Drosophila melanogaster to explore the interplay between gut bacteria and the immune system, the team focused on a receptor protein called peptidoglycan recognition protein SD (PGRP-SD). This protein belongs to a class of pattern-recognition receptors, and in 2016, the team showed that PGRP-SD detects foreign bacterial pathogens and turns the fly's immune system against them.
In the present study, the scientists turned off the gene for PGRP-SD, thus creating flies with a disrupted immune system. The mutant flies had shorter lifespans as well as an abnormally high number of the gut bacterium Lactobacillus plantarum. The scientists found that these bacteria also produced an excessive amount of lactic acid inside the fly. This, in turn, triggered the generation of reactive oxygen species, which cause damage to cells and contribute to the aging of tissues.
In contrast, when the scientists increased the production of PGRP-SD, they found that it prevented commensal dysbiosis and even extended the lifespan of the flies.
"Here we have a metabolic interplay between the commensal bacteria and the host," says senior author Bruno Lemaitre. "Lactic acid, a metabolite produced by the bacterium Lactobacillus plantarum, is incorporated and processed in the fly intestine, with the side-effect of producing reactive oxygen species that promote epithelial damage."
The researchers speculate that similar mechanisms are taking place in the mammalian intestine.