Gut Microbiome & Metabolic health

Your body is full of trillions of bacteria, viruses, fungi and other microorganisms. They are collectively known as the microbiome or microbes, for short. While some bacteria are associated with disease, others are extremely important for your immune system, heart, weight and many other aspects of health. Trillions of these microbes exist mainly inside your intestines and on your skin.

What is the gut microbiome? 

The microbes are found in a “pocket” of your large intestine called the cecum, and they are referred to as the gut microbiome. Although many different types of microbes live inside you, bacteria are the most studied. What’s more, there are up to 1,000 species of bacteria in the human gut microbiome, and each of them plays a different role in your body. Altogether, these microbes may weigh as much as 2–5 pounds (1–2 kg), which is roughly the weight of your brain. Together, they function as an extra organ in your body and play a huge role in your health. [1]

The bacteria in the microbiome help digest our food, regulate our immune system, protect against other bacteria that cause disease, and produce vitamins including B vitamins B12, thiamine and riboflavin, and Vitamin K, which is needed for blood coagulation. The bacteria living in and on us are not invaders but beneficial colonizers. Autoimmune diseases such as diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and fibromyalgia are associated with dysfunction in the microbiome. Disease-causing microbes accumulate over time, changing gene activity and metabolic processes and resulting in an abnormal immune response against substances and tissues normally present in the body. Autoimmune diseases appear to be passed in families not by DNA inheritance but by inheriting the family’s microbiome.  [2]

A person’s microbiome may influence their susceptibility to infectious diseases and contribute to chronic illnesses of the gastrointestinal system like Crohn’s disease and irritable bowel syndrome. Some collections of microbes determine how a person responds to a drug treatment. The microbiome of the mother may affect the health of her children. Researchers mapping the human microbiome are discovering previously uncharted species and genes. Genetic studies that measure the relative abundance of different species in the human microbiome have linked various combinations of microbe species to certain human health conditions. A more complete understanding of the diversity of microbes in the human microbiome could lead to new therapies, perhaps treating a bacterial infection caused by a “bad” bacteria by growing more “good” bacteria. [3]

Humans have evolved to live with microbes for millions of years. In fact, without the gut microbiome, it would be very difficult to survive. The gut microbiome begins to affect your body the moment you are born. You are first exposed to microbes when you pass through your mother’s birth canal. However, new evidence suggests that babies may come in contact with some microbes while inside the womb (4). As you grow, your gut microbiome begins to diversify, meaning it starts to contain many different types of microbial species. Higher microbiome diversity is considered good for your health (5). Interestingly, the food you eat affects the diversity of your gut bacteria.

As your microbiome grows, it affects your body in a number of ways, including

1. Digesting fiber: Certain bacteria digest fiber, producing short-chain fatty acids, which are important for gut health. Fiber may help prevent weight gain, diabetes, heart disease and the risk of cancer. (6) Fiber is the one aspect of our diet that directly feeds our gut microbiota. When we eat protein or fats for instance, we digest it and absorb it in our small intestine. In case of non-digestible fibers, we do not have the enzymes needed to break them down and digest them. Only gut bacteria can do that. Gut bacteria digest fibers and produce short chain fatty acids.Eating fiber is an essential part of maintaining good gut health. (8)
2. Helping to regulate your immune system: The gut microbiome also controls how your immune system works. By communicating with immune cells, the gut microbiome can control how your body responds to infection. (8)

Helping to regulate brain health: New research suggests that the gut microbiome may also affect the central nervous system, which controls brain function. (9)

What is gut health? Balanced vs Imbalanced Gut

“Gut health” describes the function and balance of bacteria in the many parts of the gastrointestinal tract. Ideally, organs such as the esophagus, stomach and intestines all work together to allow us to eat and digest food without discomfort. All food is ultimately broken down in the gut to a simple form that can enter the bloodstream and be delivered as nutrients throughout our bodies. This is only possible with a healthy digestive system. The incredible complexity of the gut and its importance to our overall health is a topic of increasing research in the medical community. According to Dr. E. M. Quigley, in his study on gut bacteria in the Journal of Gastroenterology and Hepatology, having a wide variety of these good bacteria in your gut can enhance your immune system function, improve symptoms of depression, help combat obesity, and provide numerous other benefits. Many facets of modern life such as high stress levels, too little sleep, eating processed and high-sugar foods, and taking antibiotics can all damage our gut microbiome. This in turn may affect other aspects of our health, such as the brain, heart, immune system, skin, weight, hormone levels, ability to absorb nutrients, and even the development of cancer.

There are some tell-tale signs of an imbalance or unhealthy gut:

1. Upset stomach: Stomach disturbances like gas, bloating, constipation, diarrhea, and heartburn can all be signs of an unhealthy gut. A balanced gut will have less difficulty processing food and eliminating waste.
2. A high-sugar diet: A diet high in processed foods and added sugars can decrease the amount of good bacteria in your gut. This imbalance can cause increased sugar cravings, which can damage your gut still further. High amounts of refined sugars, particularly high-fructose corn syrup, have been linked to increased inflammation in the body. Inflammation can be the precursor to a number of diseases and even cancers.
3. Unintentional weight changes: Gaining or losing weight without making changes to your diet or exercise habits may be a sign of an unhealthy gut. An imbalanced gut can impair your body’s ability to absorb nutrients, regulate blood sugar, and store fat. Weight loss may be caused by small intestinal bacterial overgrowth (SIBO), while weight gain may be caused by insulin resistance or the urge to overeat due to decreased nutrient absorption.
4. Sleep disturbances or constant fatigue: An unhealthy gut may contribute to sleep disturbances such as insomnia or poor sleep, and therefore lead to chronic fatigue. The majority of the body’s serotonin, a hormone that affects mood and sleep, is produced in the gut. So gut damage can impair your ability to sleep well. 
5. Skin irritation: Skin conditions like eczema may be related to a damaged gut. Inflammation in the gut caused by a poor diet or food allergies may cause increased “leaking” of certain proteins out into the body, which can in turn irritate the skin and cause conditions such as eczema.
6. Autoimmune conditions: Medical researchers are continually finding new evidence of the impact of the gut on the immune system. A healthy gut contains healthy bacteria and immune cells that ward off infectious agents like bacteria, viruses and fungi. It’s thought that an unhealthy gut may increase systemic inflammation and alter the proper functioning of the immune system. This can lead to autoimmune diseases. The immune system usually performs a protective role against bacteria and viruses. When it senses these foreign invaders, it dispatches a legion of fighter cells to attack them. In case of autoimmune diseases, the body erroneously attacks itself rather than harmful invaders. 
7. Food intolerances: Food intolerances are the result of difficulty in digesting certain foods (this is different from a food allergy, which is caused by an immune system reaction to certain foods). It’s thought that food intolerances may be caused by poor quality of bacteria in the gut. This can lead to difficulty digesting the trigger foods and unpleasant symptoms such as bloating, gas, diarrhea, abdominal pain, and nausea. There is some evidence that food allergies may also be related to gut health. [10]

There are several factors that influence gut microbiota:

1. Diet: After birth, the first effect on the gut microbiota is the infant diet (breast or formula milk). The composition of the milk has an effect on shaping the early gut microbiota (Guaraldi & Salvatori, 2012; Groer et al., 2014). In breastfeeding infants, the species that dominate the gut microbiota are Lactobacillus and Bifidobacterium; breast milk contains oligosaccharides that can be broken down easily by these species, resulting in an increase in short-chain fatty acids, which directs the immune system to increase the expression of immunoglobulin G, which neutralizes many bacterial endotoxins and viruses. (Ouwehand, Isolauri & Salminen, 2002). Whilst in infants raised on formula, the dominant species are Enterococcus, Enterbacteria, Bacteroides, Clostiridia, and Streptococcus (Yoshioka, Iseki & Fujita, 1983; Stark, Lee & Parsonage, 1982). The primary microbiota acquired during infancy may play an important role in initial immunity during the growth of babies (Groer et al., 2014; Sherman, Zaghouani & Niklas, 2014). Several studies have compared the gut microbiota population and mucosal immune response between breast and formula feeding and found that the breast feeding caused more stable population and good mucosal immune response (Grönlund et al., 2000; Bezirtzoglou, Tsiotsias & Welling, 2011). After infancy, the gut microbiota continues its development, and the diet remains key to defining the shape, structure, and diversity of the gut microbiota. Vegetarian diets have been found to be associated with healthy, diverse gut microbiota characterized by the domination of species that can foster carbohydrate fermentation and metabolize insoluble carbohydrates, such as Ruminococcus, Roseburia, and Eubacterium (Walker et al., 2011), while a non-vegetarian diet (Western diet) has been associated with a decreasing number of Firmicutes and an increase in Bacteroides (David et al., 2014). After consumption of a Western diet, the gut microbiota ferment amino acids, which result in production of short-chain fatty acids as energy sources, and harmful compounds can be produced (Windey, De Preter & Verbeke, 2012). Diet can cause important changes even over short periods (David et al., 2014). Overall total bacteria count can be increased with high-fibre diets- which provides beneficial nutrients to the gut microbiota, increases bacterial richness and boosts production of short chain fatty acids (fatty acids with fewer than six carbon atoms). Derived from intestinal microbial fermentation of indigestible foods, SCFAs are the main energy source of colonocytes, making them crucial to gastrointestinal health). (11)

• Exposure to Pathogens: Infection is one of the most common causes of dysbiosis (an imbalance between the types of organism present in a person’s natural microflora, especially that of the gut, thought to contribute to a range of conditions of ill health). Colonisation by pathogenic bacteria can induce inflammation in the gastrointestinal  tract. The inflammatory state can destabilize the gut microbiota community. In addition, pathogens can outcompete commensal bacteria, resulting in overgrowth of infectious bacteria. 
• Age: Microbial diversity increases in early childhood and stabilizes at age 3. After age 70, immune system weakness and changes in physical activity, digestion and nutrient intake can affect microbial composition. The resulting dysbiosis can result in a proinflammatory state that may be linked to health issues such as malnutrition. 
• Psychological Stress/Anxiety: Psychological stress can affect gut motility (refers to the movement of food from the mouth through the pharynx, esophagus, stomach, small and large intestines and out of the body), visceral perception (refers to the ways people feel sensations in their bodies), GI secretion (gastric juice renders food particles soluble, initiates digestion particularly of proteins, and converts the gastric contents to a semiliquid mass called chyme, thus preparing it for further digestion in the small intestine) & intestinal permeability ( how easily substances pass through the intestinal wall). These effects on the GI tract can negatively alter the gut microbiota. 
• Medication/Drug Use: Antibiotic use can diminish taxonomic diversity (various bacteria species in the gut) which can persist over time and proton pump inhibitors reduce acidity in the GI tract creating a higher pH which promotes small intestinal bacterial overgrowth. 
• Physical Activity: Habitual exercise helps with diversity & abundance of gut bacteria and boosts production of beneficial short chain fatty acids. 
• Tobacco Use & Alcohol consumption: Cigarette smoking & alcohol consumption is known to cause robust microbial shifts but more studies are needed to identify their exact impact. (12)

What is metabolic health? 

Metabolic health is described as having ideal levels of blood sugar, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and waist circumference, without using medications.  

Metabolic syndrome, refers to a group of conditions that occur simultaneously, increasing your risk of heart disease, stroke and type 2 diabetes. These conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels.

Gut microbiome & glucose metabolism

Blood glucose is a source of energy for all tissues in the body. Its levels are controlled by a complex interplay of hormones in response to different conditions, such as food intake and exercise. For example, when blood glucose dips too low, the liver releases a stored form of glucose called glycogen and it can also use amino acids to produce glucose if necessary. Glucose metabolism begins with the ingestion and digestion of carbohydrates. After the carbohydrates are completely broken down, what is left are the simple sugars: Fructose, Glucose and Galactose. Fructose comes from vegetables and fruits, while Galactose comes from dairy. Glucose sugars come from grains. Knowing where these simple sugars come from is not as important as knowing this; When Fructose and Galactose combine they make Glucose. When we measure our blood sugar, we are measuring the glucose serum in our blood. The liver is the principal site of glucose deposition after glucose feeding, while muscle and adipose tissue represent relatively minor sites of disposal of ingested glucose. This stored form of glucose is made up of many connected glucose molecules and is called glycogen. When the body needs a quick boost of energy or when the body isn’t getting glucose from food, glycogen is broken down to release glucose into the bloodstream to be used as fuel for the cells. (13)

Gut microbes influence blood glucose levels by acting directly on the liver, not by regulating the energy expenditure of specialized fat tissues, which use glucose as fuel to create heat, according to a study in mice by Weill Cornell Medicine and NewYork-Presbyterian investigators. The findings suggest modifying gut microbes may provide a new approach, which involves establishing a healthy host-bacteria relationship to managing blood glucose levels in people with diabetes and metabolic disorders. The new evidence also clarifies the scientific debate about the connection between communities of bacteria living in the intestinal tract, called the gut microbiome, and energy expenditure. The gut microbiota has emerged as an environmental factor that modulates the host’s energy balance. It increases the host’s ability to harvest energy from the digested food, and produces metabolites and microbial products such as short-chain fatty acids, secondary bile acids, and lipopolysaccharides.

Changes in the gut microbiome are associated with metabolic disorders such as obesity, insulin resistance and diabetes, conditions that involve an impaired ability to maintain proper glucose levels in the blood. (14)

Diet and exercise can change the composition and function of the intestinal microbiota. Dysbiosis can contribute to an increase in circulating and tissue resident microbial components, which can promote inflammation-induced insulin resistance. Conversely, other microbes or bacterial components can confer metabolic benefits to the host. The relationship between microbes and host metabolism is bidirectional: microbes can influence host blood glucose, but glucose levels can influence the microbiota and host response/outcomes to specific bacteria. (15)

Normally, your digestive system breaks down the foods you eat into sugar. Insulin is a hormone made by your pancreas that helps sugar enter your cells to be used as fuel. In people with insulin resistance, cells don’t respond normally to insulin and glucose can’t enter the cells as easily. As a result, your blood sugar levels rise even as your body churns out more and more insulin to try to lower your blood sugar. Insulin resistance can be promoted by gut inflammation. (14) Researchers have since shown that TNF-alpha—and, more generally, inflammation—activates and increases the expression of several proteins that suppress insulin-signaling pathways, making the human body less responsive to insulin and increasing the risk for insulin resistance. (16)

Studies suggest that the gut microbiome modulates glucose homeostasis through peripheral serotonin.

Gut Microbiome & weight gain 

Some microbes help protect us from weight gain and obesity by strengthening the gut lining and maintaining healthy metabolic markers. Akkermansia muciniphila munches on the mucus that covers your gut lining, which encourages the intestinal barrier to produce more. This makes it stronger and thicker, preventing unwanted metabolites and toxins from entering the body that would trigger an immune response and inflammation.This bacterium is more abundant in lean people and less abundant in patients with obesity. Studies indicate that Akkermansia can help the body control sugar and fat metabolism, both of which are an issue in overweight and obesity. Managing how much glucose enters your bloodstream is important. When you have healthy levels, your body uses it as energy and you don’t put on weight. But when there’s too much, insulin tells the cells to store all the extra in your fat cells — and they’re usually around the waist.  A balanced gut microbiome is linked to healthy weight. It’s probably because they maintain the gut lining, ensure appetite hormones are working correctly, and because a balanced diet with lots of plant fibers has less refined sugars and fats that encourage weight gain. (17)

Gut Microbiome & brain health

Studies in mice — and preliminary work in humans — suggest that microbes can trigger or alter the course of conditions such as Parkinson’s disease, autism spectrum disorder and more. Therapies aimed at tweaking the microbiome could help to prevent or treat these diseases, an idea that some researchers and companies are already testing in human clinical trials. A strain of Eschercihia coli makes a protein called culri, which can prompt other proteins to misfold. Some researchers suspect that these misfolded proteins transmit the error up the vagus nerve to the brain, where misfolded proteins are linked to disease symptoms. 

The bacterium Akkermancia Muciniphila makes a protein called nicotinamide, also known as Vitamin B3, that seems to travel to the brain and improve symptoms of motor neuron diseases in mice models. 

Studies in mice suggest that infection in pregnancy can set off a cascade of activity. In the mother’s gut, segmented filamentous bacteria stimulate T-helper 17 cells which are part of the immune system. They produce immune molecules that travel to the fetus’s brain and provoke autism-like behaviour. (18)

Gut bacteria can generate neuroactive compounds. In fact, it is known to make 90% of our neurotransmitter serotonin, which regulates our emotions. Conversely, the brain can transmit signals to the gastrointestinal system, for instance, to stimulate or suppress digestion. 

Gut Microbiome & heart health 

A growing body of research suggests that the wrong balance of gut bacteria can cause harm beyond your gut, playing a role in conditions as different as arthritis, obesity, and depression. It also appears to affect your blood vessels. In fact, chemicals or processes related to gut bacteria have been tied to a higher risk of heart failure, atherosclerosis (plaque buildup in arteries), and major cardiovascular events like heart attack and stroke, notes a review of studies published in March 2020 in the journal Microbiome.

Three recent studies prove that changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity and type 2 diabetes mellitus. 

Gut Microbiome & inflammation 

Numerous studies have linked the gut microbiota to inflammatory diseases. Forbes et al. (2018) have demonstrated that the immune-mediated inflammatory diseases, such as Crohn’s disease, ulcerative colitis, multiple sclerosis, and rheumatoid arthritis, change the composition of the gut microbiota. 

Studies suggest that understanding the role of macrophages in gut microbiota-inflammation interactions might offer new ways of preventing and treating inflammatory diseases. 

If you have leaky gut syndrome, it affects other aspects of your health as well. Your gut is lined by a wall, which is similar to a net with small holes in them. These small holes act as filters and enable the passage of certain substances only. It acts as a shield to keep out the bigger, harmful substances from entering your body. Lymphocytes flank the small intestine, fostering direct connection between the immune system and the gut.  When someone has a ‘leaky gut’, it means that the gut lining is damaged and cannot optimally function as a barrier any longer. The smaller holes become larger and allow harmful substances like gluten, bad bacteria, and undigested food particles to enter your system and cause considerable damage to health. The lymphocytes respond by triggering systemic inflammatory processes.The leaky gut can cause widespread inflammation and possibly elicit a reaction from the immune system.   

Research suggests that hyperglycemia elevates intestinal permeability and facilitates enteric infections and systemic inflammation, triggering the leaky gut response.

What Causes Leaky Gut Syndrome?

There are 4 main reasons for the leaky gut syndrome: 

1. Dysbiosis, or bacterial imbalance, is a leading cause of the leaky gut syndrome. It means an imbalance between helpful and harmful species of bacteria in your gastrointestinal tract.
2. Poor diet, comprising proteins found in unsprouted grains, sugar, genetically-modified foods (GMO), and dairy products.
3. Prolonged exposure to stress can weaken your immune system and inhibit your body’s ability to eliminate harmful bacteria and viruses, resulting in inflammation and leaky gut.
4. Toxin overload can lead to leaky gut syndrome. We come across more than 80,000 chemicals and other toxic substances on a daily basis. However, the main culprits are antibiotics, pesticides, aspirin, and contaminated tap water. (source)

How to improve gut health?

1. Eating a diverse range of foods: Generally speaking, a diverse microbiome is considered a healthy one. This is because the more species of bacteria you have, the more health benefits they may be able to contribute to. A diet consisting of different food types can lead to a more diverse microbiome. Unfortunately, the traditional Western diet is not very diverse and is rich in fat and sugar. In fact, an estimated 75% of the world’s food is produced from only 12 plant and 5 animal species. However, diets in certain rural regions are often more diverse and richer in different plant sources. 
2. Eat foods rich in polyphenols: Polyphenols are plant compounds that have many health benefits, including reductions in blood pressure, inflammation, cholesterol levels, and oxidative stress Human cells can’t always digest polyphenols. Because they aren’t absorbed efficiently, most polyphenols make their way to the colon, where they are digested by gut bacteria. Polyphenols from cocoa can increase the amount of Bifidobacteria and lactobacilli in humans and reduce the quantity of Clostridia. Furthermore, these changes in the microbiome are associated with lower levels of triglycerides and C-reactive protein, which is a marker of inflammation. The polyphenols in red wine have similar effects and have even been shown to increase levels of beneficial bacteria in people with metabolic syndrome. Some examples of foods rich in polyphenols are:

1. cocoa and dark chocolate
2. red wine
3. grape skins
4. green tea
5. almonds
6. onions
7. blueberries
8. Broccoli

1. Probiotics & prebiotics: 

Probiotics are live microorganisms, usually bacteria, that don’t permanently colonize the intestines in most cases. However, they may benefit your health by changing the overall composition of the microbiome and supporting your metabolism (source). 

Prebiotics are foods that promote the growth of beneficial bacteria in the gut. They are mainly fiber or complex carbs that human cells cannot digest. Instead, certain species of bacteria in the gut break them down and use them for fuel. (source)

1. Physical Activity: Recent research suggests that exercise has a number of benefits for the gut microbiota. It is linked to increases in the number of beneficial microbial species and enriching microbial diversity, as well as enhanced short-chain fatty acid synthesis and carbohydrate metabolism. Body fat percentage, muscle mass, and physical activity are significantly correlated with several bacterial populations. (source) 
2. Stress: Gastroenterologists are no strangers to the link between the brain and the gut. Patients are more likely to experience disease flares, increased inflammation and poor health-related quality of life during periods of stress. While the bacteria present in the gut have long been studied for their importance in inflammatory processes and disease activity, their nuanced roles during times of stress have only recently been examined. Part of the microbiome is bacteria lining the GI tract. Reducing stress through meditation and deep breathing techniques helps a lot with digestion, since it reduces the inflammatory response in the body caused by stress. 
3. Alcohol intake: A healthy gut achieves homeostasis or equilibrium when the good bacteria and bad bacteria balance each other out. Chronic, excessive drinking tilts the balance towards the more harmful bacteria. (source)

Conclusion

Gut microbiota, gut flora, or microbiome are the microorganisms including bacteria, archaea and fungi that live in the digestive tracts of humans. A healthy gut microbiome is a diverse microbiome. They have a profound impact on glucose metabolism, heart health and brain health. A balanced gut/good gut microbiome can be maintained by managing stress, sustained physical activity, eating a healthy diet with diverse foods and inclusive nutrients such as Probiotics. You can increase your intake of probiotics by consuming more probiotic-rich foods, including fermented foods like kimchi, kefir, sauerkraut, and yogurt. Alternatively, you can speak to your doctor about a prebiotic supplement. Many fruits, vegetables, and whole grains contain prebiotics, but they can also be found on their own. Resistant starch can also be a prebiotic. This type of starch is not absorbed in the small intestine and passes into the large intestine, where the microbiota break it down. Limiting alcohol and tobacco consumption also greatly benefits the gut microbiome.

References

1. https://www.healthline.com/nutrition/gut-microbiome-and-health#TOC_TITLE_HDR_2
2. https://depts.washington.edu/ceeh/downloads/FF_Microbiome.pdf
3. https://www.frontiersin.org/articles/10.3389/fmicb.2020.01065/full
4. https://www.healthline.com/nutrition/8-fad-diets-that-work#TOC_TITLE_HDR_2
5. https://atlasbiomed.com/blog/how-does-exercise-affect-gut-microbiome/

The contents of this article are for general information and educational purposes only. It neither provides any medical advice nor intends to substitute professional medical opinion on the treatment, diagnosis, prevention or alleviation of any disease, disorder or disability. Always consult with your doctor or qualified healthcare professional about your health condition and/or concerns and before undertaking a new health care regimen including making any dietary or lifestyle changes.