Existing in its own universe, controlling and caring for its host, the human gut contains trillions of bacteria, known as the microbiota, responsible for digesting food and regulating the immune system. This symbiotic microbiome also impacts the function and development of the central nervous system (CNS); however, little is known about the contribution of the gut microbiota during viral-induced neurologic damage. Now, a study from researchers at the University of Utah shows the gut microbiome produces metabolites which prime immune cells in the brain to destroy harmful viruses in the CNS. The team states findings suggest having a healthy and diverse microbiota is essential for quickly clearing viruses in the nervous system to prevent paralysis and other risks associated with diseases such as multiple-sclerosis (MS). The opensource study is published in the journal eLife.
Previous studies link the gut microbiota to MS, a disease caused by the immune system attacking the insulating sheath which protects neurons in the brain, slowly leading to paralysis. Whilst the cause of MS is still unknown, the common consensus is a viral infection in CNS triggers the condition, with researchers hypothesizing detrimental changes in the microbiota increases the risk of MS and other neurological diseases. The current study investigates whether gut bacteria can alter the immune response to a virus in the CNS and provide neuroprotection against the virus.
The current study utilizes a model of Mouse Hepatitis Virus, a virus known to infect cells in the mouse nervous system and causes MS type symptoms, on two groups of mice. Both groups of mice were infected with the virus, with one group of mice raised with a healthy microbiome, and the other group subjected to various microbiome disruptions, including doses of antibiotics known to eliminate many gut bacterial populations. Results show germfree mice and mice treated with antibiotics are unable to eliminate the virus and develop paralysis, having fewer microglia in the CNS. Data findings show mice with normal gut bacteria levels were able to fight off the virus and ensuing neurodegeneration.
The team then identified the metabolite gut bacteria was using to provide neuroprotection. Results show an immune signaling protein, called TLR4, influences priming of microglia in the CNS. To confirm this hypothesis TLR4 was orally administered to virally infected mice with disrupted microbiomes. Data findings show the TLR4-treated animals exhibit reduced neurological damage from the virus after infection.
The team surmises they have established that gut microbiota provides neuroprotection against neurologic damage from viral infections. For the future, the researchers state their work demonstrates the gut microbiota’s metabolites can influence microglia function to prevent CNS damage following viral infection.
Source: University of Utah Health
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