The immune system connects the gut microbiome to aging.
Humans harbour a huge array of micro-organisms both inside and outside of their bodies. Known as the human microbiota, which is primarily made up of bacteria, and also includes archaea, fungi, and viruses. Human microbiota, otherwise known as the human microbiome, is the combined genetic material of these microorganisms in a particular environment inside or outside of the human body. Now, a study from researchers at EPFL identifies a mechanism by which the immune system can cause gut microbiota to promote age-related pathologies. The team state they found that a mutation in the fruit-flies was associated with overgrowth of Lactobacillus plantarum in the fly gut and a shortened lifespan. The study is published in the journal Immunity.
Previous studies show that gut bacteria exist in virtually all animals, living in a functional balance. When this balance is disrupted, for example, due to disease or medication, this may give rise to a condition known as commensal dysbiosis, which is associated with a number of pathologies and even a decreased lifespan. However, it is unclear exactly how gut microbiota affects general health and vice versa. The current study outlines a mechanism whereby host immune dysfunction leads to commensal dysbiosis that in turn promotes age-related pathologies in fruit-flies.
The current study focuses on a receptor protein called peptidoglycan recognition protein SD (PGRP-SD) which detects foreign bacterial pathogens and turns the fly’s immune system against them. The researchers turned off the gene for PGRP-SD, creating flies with a disrupted immune system. Results show that the mutant flies have shorter lifespans than normal ones, and have an abnormally high number of the gut bacterium Lactobacillus plantarum, a widespread species of bacteria which produce lactic acid. Data findings show that the excess lactic acid triggers reactive oxygen species, which cause damage to cells and contribute to the aging of tissues.
The lab state that when they increased the production of PGRP-SD, it was observed that commensal dysbiosis was prevented, and the lifespan of the flies were extended. They go on to add that the lactic acid is incorporated and processed in the fly intestine, with the side-effect of producing reactive oxygen species which promote epithelial damage. They conclude that similar mechanisms may be taking place in the mammalian intestine.
The team surmise their study shows that a specific microbiota member and its metabolite can influence aging in the host organism. For the future, the researchers state a better understanding of microbiome-metabolic interactions during aging is needed in order to develop strategies against age-associated pathologies.