Alzheimer’s is a chronic disease that causes brain cells to degenerate and eventually die, leading to a decline in cognitive function. Patients often suffer from symptoms such as long-term memory loss, mood swings and difficulty in communicating. Unfortunately, there is currently no cure for the disease.
Scientists are still unclear about the exact cause of Alzheimer’s. Genetics, along with aging, appear to be the most significant risk factors for the disease. The composition of an individual’s gut microbiome, the community of bacteria present in the gut, also appears to be important because these bacteria are known to produce chemicals that communicate with the brain. Animal studies have also suggested that environmental factors such as noise pollution (from cars, trains, and airplanes) can cause symptoms consistent with Alzheimer’s disease and alter the gut microbiome. However, a definitive link between these factors remained elusive until now.
In this study, a team of Chinese scientists sought to better clarify the role of microbes in Alzheimer’s disease. Specifically, the team from the Tianjin Institute of Environmental and Operational Medicine wanted to uncover the relationship between chronic noise exposure, the microbiome, and aging in the development of the disease.
To investigate this link, the team used a special genetically modified mouse strain that is prone to accelerated aging and exposed the young mice to loud or soft white noise for 4 hours each day for 30 consecutive days. They then performed a variety of cognitive and laboratory tests to see if the mice showed any signs of Alzheimer’s symptoms in response to the noise.
In the first test, the team wanted to determine if chronic noise exposure in mice led to cognitive impairments similar to those seen in human Alzheimer’s patients. To assess their spatial learning ability, the team trained mice to swim to a platform hidden beneath the water from one of four different starting positions. Importantly, the pool was placed in a room with numerous visual cues to allow the mice to orient themselves towards the platform from their starting position. After three days of training, the researchers then recorded the time it took for the mice to find the hidden platform. They found that mice that had been exposed to loud chronic noise and aging mice took significantly longer to find the platform compared to the younger mice. The effect was less pronounced in mice that were exposed to lower volumes indicating that higher noise volume might contribute to more severe effects on cognition.
The team also found physical changes in the brains of both the noise-exposed and aging mice. Patients with Alzheimer’s disease often exhibit plaques in their brains that are caused by the accumulation of a protein called beta-amyloid. When researchers in this study examined the brains of the noise-exposed and older mice, they found similarly high levels of the beta-amyloid protein which suggests that chronic noise exposure, like aging, can lead to symptoms consistent with Alzheimer’s disease.
Next, the team wanted to determine if there were any changes in the gut microbiome composition of the mice that could help explain the effects of the noise exposure. They used a method called 16S rRNA sequencing which allows researchers to identify and quantify the abundance of the different bacterial species in the gut. Noise exposure caused significant changes in the bacterial community, reducing the overall diversity of species present in the gut with a marked increase in a particular bacterial species associated with inflammation.
This change in microbiome composition had important effects on the animals. For example, the team found that the noise-exposed mice showed reduced levels of two chemical messengers (GABA and 5-HT) which are produced by friendly gut bacteria and are essential for maintaining the brain’s cognitive function.
Apart from chemical messengers, some gut bacteria also help maintain the integrity of the gut and brain lining. The absence of these microbes also led to a ‘leaky’ gut lining in the noise-exposed mice. This meant that microbial components (such as bacterial cell walls), which are normally contained within the gut, can gain access to the bloodstream and cause widespread inflammation. The team thinks that this combination of inflammation and reduced gut and brain lining integrity could contribute to the accumulation of the beta-amyloid protein in the brain and explain the mental decline seen in the mice.
To further illustrate the importance of the gut microbiome composition, the team then transplanted the gut microbes from noise-exposed mice into the guts of age-matched mice that had not been exposed to noise. The researchers found that the mice receiving the transplants showed similar symptoms to the noise-exposed group, such as reduced gut and brain lining integrity as well as higher levels of beta-amyloid. These observations confirmed the team’s suspicions that the makeup of the gut microbial community can have drastic effects on the development of Alzheimer’s disease.
This study is a major step forward in helping us better understand how chronic noise exposure and aging impact the gut microbiome which, in turn, accelerates the development of Alzheimer’s disease. If confirmed in humans, the results from this study suggest that altering an individual’s gut microbiome might be an effective method for better managing the disease in the future.