Humans harbor a huge array of microorganisms both inside and outside of their bodies called the human microbiota, made up of bacteria, archaea, fungi, and viruses. The human microbiome is the combined genetic material of these microorganisms in a particular environment living in or on the host. Now, a study from researchers at EPFL identifies a mechanism used by the immune system to induce the gut microbiota to promote age-related pathologies. The team states they also identified a mutation in the fruit-flies 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 the gut bacteria exist in virtually all animals, living in a functional balance, known as symbiosis. When this balance is disrupted due to disease, diet or medication this may give rise to a condition named commensal dysbiosis, associated with a number of pathologies and even a decreased lifespan. However, it is unclear exactly how the gut microbiota affects general health and vice versa. The current study outlines a mechanism whereby host immune dysfunction leads to commensal dysbiosis leading to the promotion of age-related pathologies in fruit-flies.
The current study focuses on a receptor protein called peptidoglycan recognition protein SD (PGRP-SD) responsible for detecting foreign bacterial pathogens and regulating 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 the mutant flies have shorter lifespans than normal ones and exhibit an abnormally high number of the gut bacterium Lactobacillus Plantarum, a species of bacteria known to produce the metabolite lactic acid. Data findings show excess lactic acid triggers reactive oxygen species, causing damage to cells, contributing to the aging of tissues.
The lab states when they increased the production of PGRP-SD, it was observed commensal dysbiosis was prevented and the lifespan of the flies was extended. They go on to add the lactic acid is ingested by the fly intestine, leading to the production of reactive oxygen species that promote epithelial damage. They conclude similar mechanisms may be taking place in the mammalian intestine.
The team surmises their study identifies a specific microbiota and its metabolite capable of influencing 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.
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