From what we have learned in the last two months, a healthy microbiome is essential for good health. The gut microbiome has gained a lot of attention because of its possible role in either preventing or promoting chronic diseases, cancer and neurological disorders. These and other diseases have been linked to an imbalanced microbiome. The term that is used in describing an imbalance between the types of organisms present in the gut microbiome is called “dysbiosis.” It has also been shown that disturbing the microbiome with antibiotics can lead to disease, including infections that have become resistant to antibiotics. Microbiome studies are still too new to reveal whether certain bacteria might cause disease or whether disease might breed certain bacteria. But, the overall consensus is that the condition of the human microbiome is implicated in both health and disease.

We will study these themes in depth this month. Next month we will discuss ways to reduce the risk of disease and chronic illnesses by improving the health of our microbiome; we will learn about changes in our diet to include prebiotic foods, and adding supplements and probiotics.

IMMUNITY

Our gut microbiome has an important role in resisting the intestinal overgrowth of externally-introduced bacteria that would otherwise cause disease. These externally-introduced “bad” bacteria compete with the “good” bacteria present in the gut. It is shown that “good” bacteria, or bacteria that should be present, can release anti-inflammatory compounds that help to fight disease. Certain bacteria can strengthen the immune system.

GASTRO-INTESTINAL (GUT) DISEASES

Because most of our microbiome lives in our gut, there is a definite link between a healthy microbiome and specific diseases of the gut, including Inflammatory Bowel Diseases (IBD) such as Crohn’s Disease and ulcerative colitis. These conditions have been linked to a less diverse microbiome in the gut, which changes the immune system’s ability to combat inflammation—a key characteristic of these diseases. Dysbiosis of the microbiome is also implicated in Irritable Bowel Syndrome (IBS) and celiac disease. A normal microbiome also provides protection against C. difficile infections. C. difficile bacteria are present as part of the normal microbiome; however, when the amount of C. difficile reaches abnormal levels, it increases the risk of having a serious intestinal infection.

AUTOIMMUNE DISORDERS

The body’s immune system protects us from disease and infection. However, there is a condition in which the immune system attacks healthy cells in the body by mistake. The group of diseases where the body attacks itself is known as autoimmune disorders. There are more than 80 types; a classic sign of an autoimmune disease is inflammation, which can cause redness, heat, pain, and swelling in the part of the body that is being attacked. It has been found that an imbalance in the gut bacteria may set off alarm bells that lead the body to attack itself. For example, people with untreated rheumatoid arthritis, an inflammatory autoimmune disease, have more of a particular inflammatory bacterium in their intestines and less of a known beneficial bacterium than their healthy counterparts. Many other autoimmune diseases of the body—skin, lungs, joints, and other tissues—are also caused by inflammation. A bacterial imbalance can lead to elevated inflammation that can advance disease.

Celiac disease, the inability of the small intestine to tolerate gluten, is another autoimmune disease of the gut. Dysbiosis has been shown to be present in celiac disease patients, with a significant decrease in Gram-positive bacteria. When celiac patients eat a gluten-free diet, this bacteria restores to normal levels.

Small intestinal bacterial overgrowth, or SIBO, occurs when the normal bacteria of the microbiome expand beyond the large intestine into the small intestine, where they are not supposed to be. The cause of SIBO varies, but it often occurs when someone already has an inflammatory bowel disease, has been on antibiotics, or is diabetic. When SIBO occurs, it can lead to symptoms such as bloating, abdominal pain, diarrhea and constipation, and malabsorption of nutrients. It can precipitate autoimmune conditions such as irritable bowel syndrome. Chronic SIBO can lead to a condition called “leaky gut”, which can trigger autoimmune problems throughout the body. In leaky gut, gaps form between intestinal cells and large particles from the digestive tract enter the bloodstream, potentially triggering immune or allergic reactions. Glyphosate, an herbicide used in many GMO crops, is implicated in the rise of leaky gut in the population, as it has been shown to punch holes in the wall of the intestines. Research is still in its early stages, but evidence is mounting that the microbiome is linked to autoimmune diseases.

OBESITY

In 2014, obesity affected 600 million people worldwide. The numbers continue to increase, and obesity is considered to be a global health hazard. Many diseases arise as a result of obesity. Obesity is linked to metabolic syndrome, which is a group of conditions occurring together, that increase the risk of disease. These conditions include high blood pressure, high blood sugar due to insulin resistance, excess body weight around the waist, and high cholesterol and triglycerides. Metabolic syndrome leads to an increased risk of heart disease, strokes, type-II diabetes, liver abnormalities, low-grade inflammation, and premature mortality.

The gut microbiota helps to regulate the body’s metabolism—all the chemical processes that take place in the body in order to maintain life. Studies done in obese patients showed imbalances in a number of gut bacteria. When dysbiosis occurs, nutrients are taken into the body at an increased rate, leading to obesity. Other imbalances make the cells less sensitive to insulin, causing an increase in blood sugar levels.

MULTIPLE SCLEROSIS (MS)

Multiple sclerosis is determined to be caused by a combination of genetic and environmental factors. Given the interactions between gut microbiota and the immune system, it is plausible that certain microbes could improperly stimulate the immune system and contribute to MS. Differences have been found in the bacterial composition of people with MS versus those without. There have been noted changes in the gut bacteria of people with MS when they have had certain treatments for the illness. This is a surprising link between gut bacteria and the progression of this disease which stems from the central nervous system. There is some evidence in MS patients that certain gut bacteria that are thought to be pro-inflammatory are overrepresented, while others that are thought to be anti-inflammatory are underrepresented. Treatments that manipulate the microbiome could benefit those with MS.

GUT AND HEART HEALTH

What we eat plays a critical role in our heart health. But, how heart health is linked to our microbiome is interesting. The gut microbiome directly changes the amount and function of blood platelets. Platelets are needed if we have an injury to a blood vessel; they are involved in clotting our blood to stop bleeding. However, if platelets increase too much, a condition known as thrombocytosis, it can cause heart attacks and strokes from increased clotting of the blood. Also, when the function of platelets change, it makes them more prone to producing clots.

Here is how it works: When people ingest certain nutrients, such as choline (abundant in red meat, egg yolks, and dairy products), lecithin and L-carnitine (found in red meat as well as some energy drinks and supplements), the gut bacteria that break these nutrients down produce a compound called trimethylene N-oxide (TMAO). High levels of TMAO have been found to contribute to a heightened risk for clot-related events such as heart attacks and strokes. TMAO directly alters platelet function by increased platelet responsiveness; they become over reactive and speed up clotting rates. In one study, high blood levels of TMAO were associated with higher rates of premature death in a group of 2235 patients with stable coronary artery (heart vessel) disease. This evidence indicates that a new therapy for reducing the formation of blood clots, and decreasing the risk of heart attacks and strokes would be to avoid foods that trigger increased TMAO levels. For example, the popular Paleo diet is abundant in foods that produce TMAO.

In fact, higher blood levels of TMAO increase mortality rates from any cause by 55%. High levels of TMAO are linked to increased inflammation in the body, which can lead to many types of chronic diseases and conditions, including type II diabetes, metabolic syndrome, obesity, and Alzheimer’s disease.

To lower TMAO levels, one should avoid consuming red meats, full-fat dairy products, including whole milk, egg yolk, cream cheese, and butter; as well as nutritional supplements and energy drinks containing choline, phosphatidylcholine (lecithin), and/or L-carnitine.  Vegetarians and especially vegans, who avoid animal products, produce little TMAO. A compound known as DMB is capable of minimizing the amount of TMAO produced from our gut microbiota. DMB may be found naturally in many Mediterranean diet foods, including extra virgin olive oil.

BRAIN HEALTH

Gut bacteria has been shown to go beyond just our physical health. It is a key player in the gut-brain connection. Recent evidence proves that the gut microbiome can influence the development of the nervous system, affect brain chemistry, emotional behaviour, pain perception, and how we respond to stress.

Gut bacteria produce hundreds of neurochemicals that the brain uses to regulate many of the processes of the body, including mental processes such as learning, memory, and mood. Research has found that changing the balance between beneficial and disease-causing bacteria in an animal’s gut can alter its brain chemistry, and it can change the animal’s reactions to become bolder or more anxious. This result indicates that certain characteristics are not part of the animal’s own traits, but by the microbes that inhabit the gut. We need to ask ourselves, how much of the way we react to situations is because of our own personality traits or as a result of the state of our gut microbiome? If we find ourselves reacting in uncharacteristic ways, then it may be due to an imbalance of microbiomes. As well as our gut affecting our mental state, the bacteria in our gut can be affected by stress; even mild stress can affect the gut microbiome balance, making the individual more vulnerable to infections. How many times have you developed a cold after a particularly stressful time in your life?

Often inflammatory illnesses such as Crohn’s disease, ulcerative colitis, and irritable bowel syndrome are accompanied by anxiety and depression. In one study, mice were first infected with a parasite that triggered inflammation; as inflammation occurred it also suppressed levels of a chemical called BDNF in the hippocampus area of the brain. BDNF promotes connections between nerve cells and is an important factor in memory and mood. Adding a 10-day course of beneficial gut bacteria in these same mice showed that their behaviour normalized, as did the BDNF levels. This shows the strong impact that the gut microbiome has on the brain and behaviour.

Recently, a number of studies have explored a possible link between the gut microbiome and the neurological and developmental disorders, one of which is the group of autism spectrum disorders (ASD). Although the cause of ASD is still poorly understood, several studies have found a significant association between AS and dysbiosis in the gut microbiome. Many children with ASD have a high incidence of gastrointestinal symptoms.

Serotonin is typically known as a brain chemical, a neurotransmitter that controls and stabilizes moods.  It plays a vital role in the communication between your gut and brain. Even though serotonin is mostly associated with the brain, most of the serotonin (95%) in our bodies is found in the digestive system. Gut bacteria play a crucial role in the production of serotonin in the digestive system.  Serotonin helps control bowel movements. Altered serotonin levels can trigger irritable bowel syndrome (IBS). People with IBS who experience constipation often have lower levels of serotonin; the muscles in their rectums are less reactive to serotonin, and they are more likely to have hard or lumpy stools. Those with IBS and high levels of serotonin can have diarrhea, and their rectums are more reactive, with loose or watery stools.

CANCER

Although cancer risk is caused mostly by genetics and environment, such as lifestyle choices, microorganisms are implicated in some 20% of human cancers, particularly colon cancer, the 4th leading cause of cancer-related mortality worldwide. In the large intestine (colon), bacterial density is one million times higher than in the small intestine. 12-fold more cancers occur in the colon compared to the small intestine, implying a disease-causing role for the microbiome in colon and rectal cancers. Colon cancer appears to stem from an interaction between the microbiome, the immune system, and the epithelial cells that line the colon. One type of colonic bacteria may be a bad type; it creates three proteins that have greater potential to cause inflammation and cancer of the colon, and it is common in humans. Other bacteria produce a toxin that can trigger tumours to grow. Research is being done to determine how the proteins interact with epithelial cells to cause cancer to occur. This protein is considered useful in fighting off bacteria and fungi, but it can turn against the body and cause colon cancer. Why does this response promote cancer development? Are bacteria the reason for disease to start or do they contribute to the growth of tumours over time? These questions are yet to be answered.

There is not room enough in this article to discuss other illnesses caused by dysbiosis. Links have been found between certain bacterial populations in the gut, whether normal or disturbed, and the following diseases which have not yet been mentioned: acne, ADD, allergies, obsessional-compulsive disorder (OCD), asthma, eczema, and malnutrition.

THE ROLE OF ANTIBIOTICS

Humans are exposed to antibiotics for the treatment of infections and also through antibiotic use in livestock and crops. To decrease the use of antibiotics in Canada, a new law was passed, requiring farmers to have a veterinary prescription to use antibiotics in their animals. Doctors are taught to be mindful of antibiotic use, called “antibiotic stewardship”. This ensures that the most appropriate antibiotic is prescribed, and at the right dose and length of use, and only when necessary to fight a confirmed bacterial infection. Many people who have colds (which is a virus) ask their doctor for an antibiotic. This had led to a worsening of antibiotic resistant “superbugs”, which are resistant to most antibiotics in existence. Currently, 50% of the antibiotics that are prescribed to people are not needed or are not optimally effective (they do not kill all the disease-causing bacteria).

The number of bacteria that have become resistant to antibiotics is increasing. The danger of antibiotic resistance is that previously treatable illnesses such as pneumonia, tuberculosis, or minor infections could become incurable. This can lead to increased human illness, suffering, and death. By the year 2050, infections that were able to be cured in the past, are now predicted to lead to an estimated 2.4 million deaths in developed countries alone. What could happen is that the world will end up the way it was in the 1920s and 1930s again, before the discovery of penicillin, where more people died from infection than from any other single cause.

Along with the immediate effects on our health from exposure to antibiotics through the development of antibiotic-resistant bacteria, the use of antibiotics can also have long-term effects. The human microbiome can become a reservoir of resistant bacteria and genes. Antibiotics also affect the abundance of 30% of the bacteria in the gut community, causing rapid and significant drops in diversity and evenness.

We spoke of C. difficile overgrowth, which can lead to C. difficile infections, resulting in severe diarrhea, and even to death. It has been noted that the incidence of C. difficile infections increases when a person has been using antibiotics. Antibiotic administration disturbs the gut microbial communities and reduces their diversity. This, in turn, leads to the overgrowth of C. difficile bacteria.

Antibiotics destroy both good and bad bacteria in the gut which can lead to dysbiosis and opportunistic infections. Antibiotic-induced microbiome alterations can remain for long periods of time, spanning months and even years. These changes in the gut microbiome increases inflammation in the body, leading to a higher risk of diseases associated with increased inflammation. Studies show that there is: an increase in inflammatory bowel disease in children given antibiotics before the age of five; an increase in type 1 diabetes in children; increases in irritable bowel syndrome, metabolic syndrome, diabetes and high cholesterol in all people using antibiotic therapy. Long-term antibiotic use results in weight gain, which is the reason for its use in livestock. This implicates antibiotics as a risk factor for the development of obesity. The body also has a reduced ability to fight other pathogens, which indicates a decreased immune system response.

An altered gut microbiome can increase our risk of many different illnesses, infections, and diseases. Next month we will learn about ways to keep our microbiome healthy, with changes in our diet, and including the use of probiotics, prebiotics, and supplements.

“Our heavenly Father sent the light of health reform to guard against the evils resulting from a debased appetite, that those who love purity and holiness may know how to use with discretion the good things He has provided for them, and that by exercising temperance in daily life, they may be sanctified through the truth.” –Child Guidance, p. 396