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Gastrointestinal

The main function of the gastrointestinal (GI) system is to ensure optimal absorption and conversion of macro-and micronutrients to support cellular metabolic processes. Each anatomical section of the GI tract has unique functions with a common goal of maximizing nutrient uptake and excreting waste. The digestive system is divided into the following anatomical parts:

  • Mouth
  • Oesophagus
    • Oesophageal Sphincter
  • Stomach
    • Pyloric Sphincter
  • Small Intestine
    • Duodenum
    • Jejunum
    • Ileum
  • Large Intestine
  • Rectum

The influx of nutrients from the digestive system into the body is precisely regulated, and through the action of several enzymes, are broken down into their simplest forms. Protein, carbohydrates, and lipids are broken down into amino acids, glucose, and fatty acids, respectively. Genetic variations in the form of SNPs in the genes which are responsible for metabolizing these compounds may change the way nutrients are metabolized. 

Carbohydrate Metabolism

Glucose

Research has shown that SNPs in genes that encode several enzymes associated with glucose metabolism have pathological consequences. For example, SNPs in a gene that regulates a specific glucose enzyme lead to altered glucose metabolism and impaired glycemic control, leading to non-alcoholic fatty liver disease 1, 2. Furthermore, SNPs in genes that couple glucose and insulin signaling have shown that these individuals have a higher risk of going on to develop type II diabetes 3. Irritable bowel disease has also been shown to have a strong genetic component. Specifically, it was observed that SNPs in a specific glucose transporter predisposed individuals to this disease 4.

Protein Metabolism

Cysteine

As mentioned previously, proteins are metabolized into several amino acids that provide the building blocks for cells and tissues. Cysteine is one such amino acid that is important for protein synthesis, detoxification, as well as having diverse metabolic functions. Research has found that SNPs in the enzyme that converts cysteine to hydrogen sulfide (H2S), lanthionine, cystathionine or homolanthionine, are associated with a metabolic disease known as homocystinuria 5. Individuals with this disease have a build-up of certain amino acids in their blood which can lead to eye problems, impaired brain development, bone disorders, blood clots, and possible strokes.

SNPs that alter cysteine metabolism have also been observed in enzymes that convert homocysteine to cysteine. Individuals with these mutations present with a metabolic disease known as hyperhomocysteinemia which makes them highly susceptible to developing arterial damage and blood clots 6.

Methionine

Methionine is another important amino acid and is one of nine essential amino acids in humans. It is essential for growth and tissue repair and improves the tone and elasticity of the skin, promotes healthy hair, and strengthens nails. When its production is dysregulated due to the presence of SNPs in certain enzymes, individuals are at higher risk of developing deep vein thrombosis 7.

Many of the pathologies caused by dysregulated amino acid metabolism are easily treated through supplementation of the absent amino acid or its precursors, however, some pathologies have fewer therapeutic options as the symptoms are too severe.

The Gut-Immunity Link

Mounting evidence suggests a key role of our GI tract on general immunity 8. Our guts are colonized by millions of bacteria that aid in the digestion of food, generate essential vitamins, and most importantly, stimulate our immune systems. Recent evidence suggests that our gut microbiota can modulate inflammatory pathways that are mostly involved in, but not exclusive to, our GI tract 9.

Gut inflammation

Conditions such as irritable bowel disease, Chron’s disease, and ulcerative colitis, all stem from a hyperinflammatory response within the intestinal wall. Cytokines, which are immune proteins, play a significant role in driving this inflammation 10.

Once released from their respective immune cells, cytokines then bind to their associated receptors on other cells to elicit a response. In the case of Chron’s disease, SNPs in the receptor of a particular cytokine have been shown to correlate with childhood-onset of the disease and increased susceptibility 11, 12.

Similarly, in the case of irritable bowel disease, SNPs in the gene encoding a particular inflammatory cytokine were detected 13. The particular SNP caused the inflammatory cytokine to be over-produced in the bowel, thereby leading to a hyperinflammatory response. Interestingly, a different SNP in the same gene was shown to correlate with increased risk gastric cancer 14.

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