Exploring the link between gut dysbiosis and the development of Alzheimer’s Disease


 

Alzheimer’s Disease (AD) is well known to occur in aging individuals. It is a neurodegenerative illness characterized by the loss of specific types of neurons and synapses, which are components of our nervous system.

Alzheimer’s manifests as a progressive decline in cognitive functions and large-scale memory loss. 

The pathophysiology of how AD establishes itself is still being investigated. It is believed to be driven by the production and deposition of the “β-amyloid peptide (a.k.a Aβ)” within the brain.

The composition of these “pools” of Aβ shows different types of amyloid deposits, which correlate with the clinical status of an Alzheimer’s patient. 

Whereas the mechanisms that trigger this Aβ deposition in the brain are still being investigated. Its effect has been mapped to include: 

  • Neuro-inflammation
  • Oxidative stress
  • Mitochondrial dysfunction
  • Dysregulation of enzyme systems
  • Neuronal death

How gut dysbiosis may contribute to Alzheimer’s

We know now that the intestinal flora can influence brain activity and cause dysfunctions. Plus, the gut microbiome’s sensitivity to harmful external lifestyle and environmental factors is well known. Those considered to be important risk factors for Alzheimer’s disease include:

  • Diet
  • Sleep deprivation
  • Circadian rhythm upsets
  • Chronic noise exposure and 
  • Sedentary behavior 

In recent times it has been suggested that AD may have a connection to gut dysbiosis tracing back to various causes or conditions, including the use of antibiotics, inflammatory bowel disease (IBD), type 2 diabetes, and such. Significant qualitative and quantitative changes in the gut microbiome have been reported in AD patients. 

Alzheimer's and the gut-brain axis

The vagus nerve connects intestinal neurons with those of the central nervous system. 

The interconnectivity of the intestine, its flora, and the brain via the nervous system is well known and referred to as the “gut-brain axis.” Moreover, chemical compounds or biochemical substances produced by the gut microbiota can cross the blood-brain barrier.

These biochemical substances can reach the central neurons and influence their activity, with possible impact on behavior:

  • Biogenic amines such as serotonin, histamine, and dopamine
  • Amino acid-derived metabolites such as serotonin, GABA and tryptophan

And

  • Short-chain fatty acids (SCFAs) 

Reciprocally, gut bacteria are receptive to the messages sent by the brain in the form of neurotransmitters and neuromodulators.

A sustained inflammatory condition can contribute to Alzheimer's Disease

Certain neurotoxic compounds released by the gut microbiota, such as D-lactic acid and ammonia, can also affect the brain. So can proteins such as proinflammatory cytokines released during a state of inflammation. 

When pathogens or other harmful entities attack the system, the brain can mount an immune response. Under normal conditions, this immune response ends with the clearing out of said pathogens or cellular debris, followed by tissue restoration. However, under certain pathological conditions if the threat persists, or the immune response is compromised, a cycle of chronic inflammation results that can extensively damage neurons. 

“Neuroinflammation” occurs when the neurons themselves release substances that sustain the damaging inflammatory process and immune response. Such a prolonged neuroinflammatory response may be the cause or consequence of certain neurodegenerative diseases, including AD.

Therefore, the microbiota can heavily influence the events along the gut-brain axis by means of such immunological, neuroendocrine, and neural mechanisms, culminating in cognitive dysfunction typical of AD. 

 

 

Author: Ranjan Sinha


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