In recent years, genetic testing technology has evolved, making it possible to learn more about an individual’s physical constitution and disease risk. At the same time, research into the effects of intestinal flora (intestinal bacterial flora) on health and disease has also progressed rapidly. In particular, attention has been focused on the relationship between genes and intestinal flora, raising questions such as “Does one’s genes determine the composition of one’s intestinal flora?” and “Does intestinal flora affect gene expression?”
In this article, we will explain in detail everything from the basics of genetic testing to its relationship with intestinal flora, and delve deeper from a scientific perspective, including the latest research results.
What is genetic testing?
1. The basic role of genes
DNA (deoxyribonucleic acid) is a molecule that can be considered the blueprint of life, and determines all the characteristics of our bodies. DNA is made up of approximately 3 billion base pairs, and specific sequences within it (genes) code for proteins, thereby regulating the functions of our bodies.
2. How genetic testing works
In genetic testing, DNA is extracted from samples such as saliva or blood, and the base sequences of specific genes are analyzed. This analysis can reveal an individual’s physical constitution, disease risk, metabolic characteristics, and so on.
3. What genetic testing can tell you
Genetic testing can provide information such as:
Risk of disease (diabetes, cancer, Alzheimer’s, etc.)
Physical constitution (ease of gaining weight, ease of muscle building, alcohol tolerance, etc.)
How well a drug works (how quickly a particular drug is metabolized)
This will enable optimal health management and dietary improvements for each individual.
What is intestinal flora?
1. Composition of intestinal flora
There are more than 100 trillion bacteria living in the intestines, which are called the “intestinal flora.” The intestinal flora is broadly classified into the following three groups:
Good bacteria (bifidobacteria, lactic acid bacteria, etc.): Improves intestinal environment and strengthens immunity
Bad bacteria (Clostridium perfringens, E. coli, etc.): Produces harmful substances and worsens the intestinal environment
Opportunistic bacteria (Bacteroides, Clostridium, etc.): Can be either good or bad depending on the environment
2. The role of intestinal flora
Your gut flora has the following effects on your health:
Promoting digestion and absorption (breaking down dietary fiber, producing short-chain fatty acids)
Adjustment of immune function (suppression of pathogens, activation of intestinal immunity)
Interaction with the brain (the gut-brain axis influences mental health)
Metabolism and weight management (link to obesity)
The intestinal flora changes depending on diet and lifestyle habits, and has a significant impact on an individual’s health condition.
The relationship between genes and intestinal flora
1. The influence of genes on the composition of gut flora
Recent research suggests that the composition of your gut flora is determined in part by genetic factors
Association between genetic polymorphisms and intestinal bacteria
It is known that certain genetic mutations (SNPs: single nucleotide polymorphisms) affect the diversity of intestinal flora and the presence of certain bacteria. For example, it is known that mutations in the FUT2 gene affect the establishment of bifidobacteria (Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571975/ ).
Hereditary diseases and intestinal flora
It has been revealed that intestinal diseases such as ulcerative colitis and Crohn’s disease are related to genetic factors and changes in the intestinal flora.
2. Effect of gut flora on gene expression
On the other hand, it has also been suggested that intestinal flora may affect epigenetics (control of gene expression) .
-Effect of short-chain fatty acids
Short-chain fatty acids (butyric acid, acetic acid, propionic acid, etc.) produced by intestinal bacteria are thought to cause epigenetic changes such as DNA methylation and histone modification, and regulate the expression of genes involved in inflammation and metabolism (Reference: https://www.nature.com/articles/s41575-018-0061-2 ).
・Gut flora and neurotransmitters Gut bacteria are also involved in the production of neurotransmitters such as serotonin and dopamine, which have been suggested to affect mental illness and stress responses.
Utilizing genetic testing and intestinal flora analysis
In recent years, the combination of genetic testing and gut flora analysis has made it possible to provide more personalized health management. For example:
Based on individual genetic information, we propose optimal intestinal health (dietary advice, selection of probiotics)
Predicting future disease risk based on intestinal flora analysis
Proposing nutritional intake balance suitable for each individual
This will enable individually optimized health management, contributing to disease prevention and improved wellness.
Types of intestinal flora and individual differences
The composition of the intestinal flora varies greatly from person to person. This is because not only genetic factors but also lifestyle, diet, and environmental factors are involved. The composition of the intestinal flora is determined immediately after birth by the transfer of bacteria through the mother’s birth canal and breast milk, and changes as the person grows depending on their diet and living environment.
1. Classification of intestinal flora by type
Recent research has shown that gut flora patterns can be broadly classified into three types:
Enterotype 1 (Bacteroides)
Common in Western diets that include a lot of meat and fat
Activated protein and lipid metabolism
A link has been suggested with inflammatory bowel disease and diabetes.
Enterotype 2 (Prevotella type)
Common in people who eat a lot of plant-based foods and carbohydrates
Produces a lot of short-chain fatty acids and maintains a good intestinal environment
Associated with reduced risk of cardiovascular disease
Enterotype 3 (Ruminococcus)
Common in people who eat a balanced diet
Involved in the fermentation of dietary fiber and maintains pH balance in the intestines
Although these types are to some extent genetically determined, they can be modified to some extent by diet and taking probiotics.
2. The influence of genes on gut flora diversity
Several studies have shown that genes influence the diversity (balance) of gut flora.
For example, a twin study comparing identical and fraternal twins found that the composition of the gut flora of identical twins was more similar (reference: https://www.nature.com/articles/nature07540 ). This result suggests that genes play a role in the composition of the gut flora to some extent.
It has also been found that certain genes affect the types and diversity of intestinal bacteria. For example, it has been found that polymorphisms in the LCT (lactase) gene determine whether or not lactose can be broken down, which in turn leads to differences in the types of bacteria present in the intestines (Reference: https://www.cell.com/cell/pdf/S0092-8674(18)30155-2.pdf ).
The relationship between intestinal flora and disease
1. Intestinal flora and obesity/diabetes
The composition of gut bacteria is closely related to obesity and diabetes, especially the ratio of Firmicutes to Bacteroidetes.
People with a high Firmicutes phylum: High energy absorption efficiency and prone to obesity
People with a lot of Bacteroidetes: They have low energy absorption efficiency and are prone to losing weight
Research has shown that this ratio is not only influenced by diet but also determined to some extent by genes. For example, it has been reported that people with the FTO gene (an obesity-related gene) tend to have a higher proportion of Firmicutes (Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270213/ ).
In addition, a study examining the intestinal flora of diabetic patients confirmed that their intestinal diversity was reduced compared to healthy individuals. In particular, a lower number of butyrate-producing bacteria (Faecalibacterium prausnitzii) is thought to be associated with the risk of type 2 diabetes .
2. Gut flora and mental illness
The intestinal flora and the brain are closely related through the gut-brain axis , and it is known that the intestinal environment also affects mental health.
Patients with depression and anxiety disorders have low gut flora diversity
Decreased levels of certain Lactobacillus and Bifidobacterium bacteria
In particular, research has shown that a decrease in the production of short-chain fatty acids (butyric acid) and neurotransmitters (GABA, serotonin) produced by intestinal bacteria can lead to lower stress tolerance and worsening depressive symptoms (Reference: https://www.nature.com/articles/s41564-018-0337-x ).
Interestingly, it has been pointed out that the risk of mental illness may be affected by interactions between genes and gut flora. For example, it has been shown that the BDNF gene (brain-derived neurotrophic factor) and the composition of gut bacteria mutually influence cognitive function and stress response.
Application to personalized medicine
Combining genetic testing with intestinal flora analysis makes it possible to provide individually optimized health management.
Combining genetic testing with intestinal flora analysis makes it possible to provide individually optimized health management.
Selecting probiotics according to the state of your intestinal flora
Predicting disease risks and developing individual preventive measures
In this way, approaches that take into account the interactions between genetic information and intestinal flora are making it possible to provide more precise personalized medicine.
The relationship between changes in intestinal flora and aging
The composition of the intestinal flora changes throughout life. It is known that the diversity of the intestinal flora decreases with age. This is thought to be due to factors such as a decline in immune function, changes in diet, and reduced physical activity.
1. Intestinal flora in childhood
The intestines of a newborn baby are sterile, but bacteria present in the mother’s birth canal and skin are transferred during childbirth, forming the intestinal flora. In particular, the oligosaccharides contained in breast milk have the effect of increasing bifidobacteria, and bifidobacteria often predominate in breastfed babies.
It has also been reported that the method of birth affects the intestinal flora . Babies born naturally are more likely to inherit their mother’s intestinal bacteria, whereas babies born by Caesarean section have more bacteria derived from the skin and tend to have different development of intestinal flora. It has been suggested that this difference may be involved in the development of immune function and the risk of developing allergies (Reference: https://www.nature.com/articles/s41586-019-1560-1 ).
2. Gut flora in adults
The intestinal flora of adults is relatively stable, and although it is affected by diet, stress, exercise habits, etc., it maintains a certain degree of balance.
In particular, the balance of your intestinal flora can change significantly depending on your diet . For example:
A diet rich in dietary fiber → Increases good bacteria (bifidobacteria and bacteroides)
High fat and high protein diet → Increase in bad bacteria (such as Clostridium)
3. Intestinal flora in old age
As we age, the composition of our intestinal flora changes and its diversity decreases, particularly with a decrease in the number of bacteria that produce butyrate (e.g., Faecalibacterium prausnitzii) .
Butyrate maintains the intestinal barrier function and plays a role in suppressing inflammation. Therefore, a decrease in butyrate-producing bacteria with age is thought to be related to colitis, irritable bowel syndrome (IBS), and even cognitive decline (Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641835/ ).
Latest research on the relationship between genes and gut flora
In recent years, research into the gut flora has progressed rapidly, and knowledge about the interactions between genes and gut bacteria is increasing. Below are some notable research findings.
1. Genes may determine gut bacterial colonization
A study from Harvard University and Massachusetts Institute of Technology (MIT) has revealed that certain genes influence the colonization of certain gut bacteria.
This study compared the genes and gut flora of thousands of subjects and found that people with the LCT gene (lactase gene) can consume dairy products and therefore have more bacteria in their intestines that break down lactose (Reference: https://www.science.org/doi/10.1126/science.aar6231 ).
It has also been reported that people with a mutation in the FUT2 gene have difficulty establishing bifidobacteria. This gene produces mucin (mucus) in the intestines, and it is thought that changing the composition of mucin makes it easier for certain bacteria to establish in the body.
2. Influence of gut flora on epigenetics
The relationship between epigenetics (control of gene expression) and intestinal flora is also attracting attention.
For example, it has been suggested that short-chain fatty acids (SCFAs) produced by gut bacteria induce epigenetic changes such as DNA methylation and histone modification , which may suppress the expression of inflammation-related genes.
It has also been reported that metabolites produced by intestinal bacteria regulate the activity of cancer suppressor genes (such as p53) . In particular, colon cancer patients often have an imbalance in their intestinal flora, and it has been pointed out that an increase in inflammation-causing bacteria (such as Fusobacterium nucleatum) may promote the progression of cancer (Reference: https://www.nature.com/articles/s41591-019-0637-7 ).
Improving intestinal flora and utilizing genetic factors
Combining genetic testing with intestinal flora analysis will enable more precise health management. In particular, the use of probiotics and prebiotics may help to compensate for genetic disadvantages.
For example, people with FUT2 gene mutations have difficulty in establishing bifidobacteria, so taking certain prebiotics (such as oligosaccharides) can promote the growth of bacteria. Also, people who cannot break down lactose due to the LCT gene can improve their intestinal environment by taking fermented foods that contain a lot of lactic acid bacteria (such as yogurt and kimchi).
Interactions between the gut flora and the immune system
The intestinal flora is closely related to the immune system. Not only is the intestine also known as the “second brain,” but it also contains approximately 70% of the body’s immune cells , and serves as the first line of defense against external pathogens. Proper functioning of the intestinal flora can help maintain immune balance and reduce the risk of developing autoimmune diseases and allergies.
1. The relationship between intestinal flora and innate immunity
Gut bacteria send important signals to the immune system and regulate the function of immune cells. In particular, it is known that the gut flora influences both innate and adaptive immunity .
Innate immunity (the immune system we are born with)
Intestinal bacteria interact with intestinal epithelial cells and macrophages to regulate inflammatory responses.
Toll-like receptors (TLRs), a type of immune cell, recognize patterns of intestinal bacteria and induce appropriate immune responses.
Adaptive immunity (immunity acquired later in life)
Metabolic products of intestinal bacteria (such as short-chain fatty acids) promote the differentiation of regulatory T cells (Treg) and prevent excessive immune responses.
An increase in good bacteria promotes the secretion of IgA antibodies and prevents the invasion of pathogens into the intestines.
2. Intestinal flora and autoimmune diseases
Autoimmune diseases develop when the immune system attacks one’s own cells, and involve a complex interplay of genetic and environmental factors. Recent research has revealed that the intestinal flora influences the risk of developing autoimmune diseases .
Rheumatoid Arthritis (RA)
It has been confirmed that the intestinal flora of patients with rheumatoid arthritis has abnormally high amounts of the bacterium Prevotella copri (Reference: https://www.nature.com/articles/nm.3245 ).
An increase in P. copri may increase intestinal permeability and promote the secretion of inflammatory cytokines (IL-6 and TNF-α), potentially causing immune system abnormalities.
Type 1 diabetes
The intestinal flora of patients with type 1 diabetes tends to have a reduced number of butyrate-producing bacteria and impaired intestinal barrier function.
It has been found that the intestinal flora of patients with multiple sclerosis contains more bacteria that cause inflammation and fewer bacteria that have anti-inflammatory effects (Reference: https://www.cell.com/cell-reports/fulltext/S2211-1247(17)31189-4 ).
The relationship between intestinal flora and cancer
Research into the relationship between intestinal flora and cancer is also progressing. In particular, a strong link with colon cancer has been suggested, and improving the intestinal environment may be helpful in cancer prevention.
1. Intestinal flora and colon cancer
A study examining the intestinal flora of colorectal cancer patients found that certain bacteria are associated with the risk of developing colorectal cancer.
Fusobacterium nucleatum
It has been shown to be increased in the intestines of patients with colorectal cancer.
It increases the risk of cancer by producing inflammatory toxins and destroying the intestinal barrier function.
This toxin can cause inflammation in the colon mucosa and induce DNA damage.
On the other hand, it has been suggested that taking probiotics (such as lactic acid bacteria and bifidobacteria) may reduce the risk of colon cancer . For example, it has been reported that butyric acid produced by fermentation of lactic acid bacteria has the effect of suppressing the proliferation of cancer cells (Reference: https://www.nature.com/articles/s41575-018-0061-2 ).
2. Intestinal flora and immunotherapy
In recent years, immune checkpoint inhibitors (e.g., PD-1 inhibitors) have been attracting attention in cancer treatment, but it has been pointed out that their effectiveness may be influenced by intestinal flora.
A French research team compared the intestinal flora of patients who responded well to immune checkpoint inhibitors with those who did not, and discovered that patients with higher levels of a type of bacteria called Akkermansia muciniphila responded better to treatment (Reference: https://science.sciencemag.org/content/359/6371/91 ).
Summary
The relationship between genetic testing and intestinal flora has become increasingly clear in recent research. Genes affect the composition of the intestinal flora, while the intestinal flora is involved in gene expression, immune function, metabolism, and even mental and neurological disorders. It has been shown that an imbalance in the intestinal flora increases the risk of obesity, diabetes, autoimmune diseases, colon cancer, and neurological disorders. It is expected that the combination of genetic testing and intestinal flora analysis will lead to individually optimized health management and preventive medicine.
