Gut Microbiome, Alzhimer’s Disease, Oxidative stress & Gut-Brain axis: Are they interrelated?

Our Gut microbiome houses about 100 trillion microorganisms including at least 1000 different species of bacteria & involved in various biological & physiological functions inside our body. As discussed in previous blogs, gut imbalance( or gut dysbiosis) is the primary reason for development & progression of life threatening diseases such as Alzhimer’s, Parkinson, Type 2 diabetes mellitus & depression. In this blog we are going to discuss the role of Gut Microbiome in development of Alzhimer’s disease.

In humans about 33% of gut microbiota is common while the major 2/3rd is different from one individual to others, testifying the unique identity of an individual. In Adults, a healthy microbiota is characterized by community  stability & species diversity.The Firmicutes (such as Lactobacillus) and the Bacteroides represent the main bacterial phyla in the gut followed by Proteobacteria, Actinobacteria (such as Bifidobacterium), and Cyanobacteria. This microorganism community( when in right composition & diversity)holds a beneficial relationship with the human body. Therefore, an imbalance in gut bacteria or referred to as Gut Dysbiosis, can result in a number of diseases ranging from inflammatory bowel syndrome, obesity, diabetes, asthma, Parkinsons, Alzhimer’s, Autism & even depression.

Gut-Brain Axis

It is a known & researched fact that both our nervous system & digestive system talk to each other. Millions of nerves end in the gastrointestinal tract mucosa, constituting the enteric nervous system which regulates the intestinal functions and communicates with the brain through the vagus nerve. This vagus nerve is responsible for two way communication signals from brain to gut & vice  versa. Since our human body is bi-directional, whatever happens in gut does not stay in the gut, it goes everywhere, gut dysbiosis, causing the breakdown of the intestinal permeability, can lead to an inflammatory condition not limited to the gut, but can reach to the bloodstream & brain. This intestinal permeability has serious consequences and has been linked to several chronic disorders such as type 2 diabetes, Alzhimer’s & depression. Besides cytokines, there are many other transmitters/mediators that send messages to the brain through the vagus nerve.

In fact, after having high fat & carbs meals, enteroendocrine cells, specialised intestine cells, release hormones & peptides. These mediators play important biological functions including improving cognition & glucose metabolism. Interestingly high fat diets can reduce production of short chain fatty acids specifically Butyrate & has been linked to higher risk of developing type 2 diabetes given that SCFAs are involved in neurotransmission. It  modulates the synthesis of several neurotransmitters regulating behaviour and cognition. In particular, both butyric and propionic acid enhance the expression of tyrosine and tryptophan hydroxylase, enzymes involved in the synthesis of dopamine, noradrenaline, and serotonin( happiness hormones, it is fact that our gut produces 90% of the serotonin) giving signals to brain. In short, our gut & brain communicate with each other in intertwined ways through production of metabolites, cytokines & neurotransmitters. It is a proven fact that our gut may play an important role in development of chronic diseases such as Alzhimer’s , depression & diabetes . You can learn more about gut-brain axis here.

Gut & Oxidative Stress

Our gut plays an important role in Oxidative Stress & has rich sources of Nitric Oxide(NO). High Nitrate intake increases nitrite concentration & nitric oxide.Excessive NO production is associated with neuro-inflammation, cellular damage, axonal degeneration, and neurodegenerative disorders.An aberrant production of NO leads to detrimental effects due to the generation of reactive oxygen species (ROS). This can lead to damage of DNA. ROS & RONS (reactive oxygen nitrogen species) are produced in mitochondria, the energy production house of the human body that produces ATP( through oxidative reactions). Needless to mention here that gut & mitochondria interact with one another. Gut bacteria microbolites, specifically Short chain fatty acids (SCFA) influences mitochondrial function to reduce ROS production. Therefore, our gut has a role to play in Oxidative stress. On the other hand pathogens/toxins can result in production of hydrogen sulphide in the gut. High level of hydrogen sulphide production is associated with negative effects in the human body including shifting of metabolism towards glycolysis, thereby leading to reduced ATP production & over-expression of proinflammatory mediator genes. Needless to mention here that healthy microbiome is building block for overall holistic health.

Alzheimer’s Disease

Around 50 million people are impacted globally by dementia. Alzheimer disease is the most common form of dementia among elderly population. During the initial stages of this disease, the most common & prevalent symptom is memory impairment followed by cognitive issues leading to loss of abilities of daily activity. Currently, Alzheimer is considered to be a slow chronic progressive brain disease that can be diagnosed several years before the clinical onset. Role of several genetic & modifiable environmental & behavioural risk factors has been identified.Among these modifiable factors, the role of gut microbiome in managing low grade inflammation holds a prominent place.

Alzheimer disease may be caused by abnormal build of a protein in the gut that gradually spreads to the brain.In people with Alzheimer’s disease, a protein called beta-amyloid clumps together in the brain to form plaques that disrupt normal brain processes. 

The increased permeability of the gut due to gut dysbiosis may result in neurodegenerative disorders, especially those associated with ageing such as Alzhimer’s. Besides gut bacteria can secrete large amounts of lipopolysaccharides(LPS) or toxins, which can contribute to the production of proinflammatory cytokines associated with development of Alzheimer’s.

Besides, the relationship of the gut microbiome and diet to neurodegenerative diseases suggests that Alzheimer’s disease is associated with specific changes in gut bacteria and that a type of ketogenic Mediterranean diet can affect the microbiome in ways that could impact the development of dementia.

Learning how changing your gut bacteria diversity can help you prevent occurrence of this dreaded disease. Sign up for our gut intelligence solution here. 

Source: https://www.hindawi.com/journals/omcl/2019/4730539/ ; https://www.researchgate.net/publication/315790252_The_Gut_Microbiota_and_Alzheimer’s_Disease