Author: Yasmin Yong
Artist: Yasmin Yong
Editor: Haytham Malik
Alzheimer’s Disease continues to stand as a pressing and enigmatic global health concern. It is characterised by the accumulation of extracellular β-amyloid and intracellular tau protein deposits, which leads to synapse loss and neuronal death. However, the pathophysiological mechanism remains largely unknown, hindering the development of much-needed treatments and cures.
Interestingly, recent progress in scientific research has brought forth new advances in our understanding of this disease. Contrary to prior belief, the causes of Alzheimer’s are not limited to the brain. New theories suggest origins from other parts of the body. Notably, current findings indicate an intricate relationship exists between the gut and the brain, where complexities within the gut microbiome directly impact brain health.
So, how are the gut and brain linked?
There is a microbiota-gut-brain axis consisting of bidirectional neural and metabolic pathways. Certain bacteria are believed to directly interact with the mechanisms of behaviour and cognition through this axis. Our gut microbiome is a complex ecosystem of 100 trillion bacteria. If there is dysbiosis, imbalance within the gut can manifest issues within the brain.
Gut bacteria and neurodegeneration
When our body is infected, or injured, it responds with inflammation, a natural defence that involves our organs and tissues. However, this immune response is also seen in the brain and the spinal cord, and is known as neuroinflammation. This type of inflammation is significantly associated with detrimental decline in cognitive functioning, from thinking to memory, as well as neurodegenerative diseases.
Inside our brain, there are special immune cells called microglia that act as a defense system. Via homeostasis they maintain a healthy brain environment and defend against attacks by foreign molecules–either by phagocytic action and the release of proinflammatory cytokines. If microglia are sustained in their active state for too long, defined as an amplified inflammatory response, this can lead to neuronal degeneration, build-up of amyloid deposition, and even brain shrinkage. These pathological changes are often seen as we get older, and are strongly correlated with Alzheimer’s Disease.
Eating foods with high fibre, like fruits and vegetables, allow certain gut bacteria to reduce inflammation by making and releasing short-chain fatty acids (SCFAs). These SCFAs send signals through the gut-brain axis and have anti-inflammatory properties. Studies on ageing mice have supported this–more fibre in their diet increased SCFA concentration, which helped limit neuroinflammation. In another study, when SCFA mixtures were administered to post-stroke aged mice, they found a significant reduction in brain and gut inflammation, as well as improved behaviour. Gut bacteria are also involved in the formation of amyloid, which in turn potentially affects the amount of amyloid plaque in the brain. Interestingly, high levels of SCFAs seem to have a link to lower chances of Alzheimer’s and similar memory problems. Therefore, SCFAs are believed to be linked to the reduced risk of Alzheimer’s and other dementias.
In contrast, other bacteria in the gut can release lipopolysaccharides, which induce microglial activation and, thus, inflammation. Therefore, it is evident that different bacterial actions interplay in the mechanisms of neurodegenerative disorders.
Our genes can also play a part in forming the community of our gut bacteria. Recent research has found connections between specific gut bugs and genes linked to Alzheimer’s risk, like the Apolipoprotein E ε4 gene. For instance, having lots of Collinsella bacteria in the gut might go along with having a gene that raises the risk of Alzheimer’s (APOE risk), leading to more inflammation in the body.
What is the significance of all of this?
Our brain’s health is influenced by a mix of our genes, gut bacteria, what we eat, and how our bodies process fats.This holistic approach to understanding and managing Alzheimer’s has introduced potential ideas for new ways to prevent it. Nutrition experts believe high-fibre diets such as the Mediterranean Diet have neuroprotective properties and so might protect our brains by defending against neuroinflammation.
As scientists conduct more research into this connection between our gut and brain, it is becoming increasingly apparent that what we eat doesn’t just affect our bodies—it has an acute impact on our brains too. This poses an advancing area of study, and it is paving future avenues for scientists to explore with larger cohorts, harnessing a key to potentially transform the future of Alzheimer’s Disease treatment and prevention.
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