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The Intersection of Genetics and Microbiome

Our understanding of human health continues to grow and evolve. As we learn more about the relationship between our genetics and the bacteria that reside in our digestive tract, exciting new opportunities emerge for improving patient outcomes through personalized care.

The Gut Microbiome: A Vital Organ System

The gut microbiome is a complex community of trillions of microorganisms, including bacteria, fungi, and viruses, that live in the intestines. It plays a critical role in digestion and absorption, immune function, and metabolism. The main phyla of the gut microbiota belong to Bacteroidetes and Firmicutes. Changes in the abundance of each of these phyla, specifically a reduced presence of Bacteroidetes paired with an increased presence of Firmicutes, have been associated with obesity.  

The composition of our gut microbiome changes throughout life and has numerous health implications. Recent research highlights that its influence extends beyond the functions directly related to digestion, as it has been been found to also have influences on our genetic makeup. 

Cross Talk Between Our Genes and Microbiome

Our genes can influence the composition of our microbiome, and in turn, the microbiome can impact gene expression and activity. How our gut bacteria interact with our immune system and the chemicals they produce can change how our genes are turned on or off. These bacteria can also influence our genes in other ways that don't involve changing the actual DNA.

FUT2 (fucosyltransferase 2) is an example of our genetic influence on the gut bacteria. FUT2 polymorphisms determine whether an individual is a "secretor" or not. Secretors are those who have a functional FUT2 gene allowing them to express their ABO blood group antigens in their fluids or secretions. Secretors tend to have higher levels of beneficial bacteria and a lower risk for inflammatory bowel disease. Variants in this gene can influence the diversity of gut bacteria, which impacts digestion, immunity, and, ultimately, the risk of infectious and inflammatory disease. 

On the other side, short-chain fatty acids (SCFAs), which are produced by the fermentation of dietary fibers by gut bacteria, affect genes related to metabolic health, inflammation, and brain function. SCFAs have been shown to modulate the expression of genes like TPH2 (tryptophan hydroxylase 2), which is involved in serotonin production. This is what links gut health to mood and mental well-being.

More Genetic Implications

APOE (Apolipoprotein E) genotype affects the composition of the gut microbiome and is associated with lipid metabolism and Alzheimer’s risk. Similarly, FTO (fat mass and obesity-associated gene), a key regulator of body weight, is influenced by microbiome-derived metabolites, suggesting that targeting gut health may help mitigate the effects of genetic predispositions to obesity.

Furthermore, research has identified that vitamin B12 levels could be significantly influenced by genetic variations in CUBN (cubilin) and FUT2. Altered vitamin B12 levels may disrupt folate metabolism, potentially leading to the development of congenital heart disease. This underscores the importance of considering genetics and microbiome health when making clinical decisions for your patients.

Practical Recommendations

• Use genetic testing to identify gene variants that may be impacting imbalances in the gut microbiome.

• Consider recommending probiotic and prebiotic supplements for patients with specific genetic variants, such as FUT2 secretor status, to support gut microbiome diversity.

• Encourage a diet of fiber-rich foods to promote SCFA production, particularly for patients with variants in FTO or APOE who may benefit from microbiome-driven metabolic support.

• Promote testing of the gut microbiota composition to pair with genetics testing and create even more precise, personalized nutrition and supplement recommendations.

Summary

The intricate relationship between genetics and the gut microbiome plays a crucial role in influencing health and disease. Understanding how our genes shape the microbiome and how gut bacteria, in turn, affect gene expression opens new opportunities for personalized care. By integrating genetic testing, tailored dietary recommendations, and microbiome support, healthcare professionals can optimize patient outcomes and address specific health concerns more effectively.

Stay at the forefront of personalized healthcare with Scylex! Partner with us to bring advanced nutrigenomic insights to your practice and help your patients take control of their health with personalized, gene-based care.