The microbiota residing in the human gut consists of over 1000 different microbial species whose genetic material, known as the microbiome, is approximately 150 times greater than that of human genome. It is now known that these genes encode for a range of proteins, enzymes, peptides and other signalling molecules that serve essential functions in the human body. The metabolic capacity of the microbiome far outweighs that of the human genome. What appears to be important for health is that the gut microbiota is diverse, with a large amount of different commensal (beneficial) species and low numbers of pathogenic ones. The greater the diversity, the better the metabolic capacity. (4, 5).
A key function of the gut microbiota is to digest dietary fibre (which is their main source of energy) and convert it into metabolites, known as short chain fatty acids (SCFAs). There are three main SCFAs; butyrate, propionate and acetate. The main role of acetate is to help the growth of healthy bacteria and provide a substrate for the production of more SCFAs. Butyrate and propionate are responsible for many of the essential functions performed by the gut microbiota, both at the level of the gastrointestinal tract and in organs throughout the body. These functions include maintaining the integrity of the gut wall, modulating immune function, assisting with detoxification, supporting mitochondrial and metabolic function and influencing energy homeostasis, appetite control and brain function.
Other metabolites produced by the gut microbiota include vitamins, polyphenols and neurotransmitters, all of which influence our physiology (6, 7, 8, 9).
The Gut Microbiota and Gut Wall Integrity
Butyrate provides approximately seventy percent of the energy used by enterocytes, the cells that line the gastrointestinal tract (10). This energy is used for cell renewal and function, and is therefore essential for maintain the health of the gut wall. Butyrate can also activate certain genes that allow these cells to serve their intended function (11). For example, the goblet cell, a type of enterocyte, produces mucin, which is a component of mucus, the protective layer that coats the gut wall. Mucus helps prevent the passage of antigens (foreign substances) from the gut lumen into the circulation. Butyrate provides energy for goblet cells and it also activates a gene responsible for the production of a protein involved in mucin synthesis (12). In other enterocytes, butyrate activates genes that are responsible for the production of tight junction molecules (12). Tight junctions form the cement between enterocytes and prevent the passage of antigens into the circulation. In this way, SCFAs are able to help maintain the health and integrity of the gut wall.
An important fact to note is that the mucus layer of the gut wall contains carbohydrates. These carbohydrates can be digested by the gut microbiota if dietary fibre is inadequate. This leads to a breakdown of the mucus layer, exposing the enterocytes to antigens in the gut lumen. Dietary fibre is therefore essential for healthy diversity of gut microbiota (with fibre being food for good bacteria) and for maintaining the mucus layer and gut wall integrity.
Short- Chain Fatty Acids and Immune Function
Another essential role of SCFAs is to stimulate a healthy immune response. The gut wall contains approximately eight percent of our immune cells. These cells are located between enterocytes, within lymph nodes or within areas called peyer’s patches – all of which are present along the entire gastrointestinal tract (13, 14).
SCFAs attach to receptors on these immune cells and activate them in order to produce a well-controlled immune response should they come in contact with any antigens or pathogens. When the gut microbiota has a healthy diversity, this response is mild and self-limiting and is known as a state of “immune tolerance”. Immune tolerance is beneficial to the host as it quickly and effectively deals with foreign substances without causing damage to the gut or other tissues (13, 14).
Other Functions of the Gut Microbiota
The gut microbiota also influence other functions in the body by
Modifying genetic activity in various cells throughout the body (11, 14).
Improving the absorption of essential nutrients (15).
Supporting the function of mitochondria, the organelle that provides energy to cells (16,17).
Producing vitamins that are used by gut microbiota and host cells (eg b-group vitamins and vitamin K) (18,19).
Increasing the bioavailability of dietary antioxidants (20).
Assisting detoxification by secreting enzymes that neutralize ingested toxins (21-23).
Up-regulating the production of detoxification enzymes in enterocytes and liver cells (21-23).
Stimulating enterocytes to produce molecules and neurotransmitters that are responsible for regulating appetite and energy balance (24-28).
Sending signals to the brain via the Vagus nerve and neuroendocrine system. This communication is known as the gut-brain connection (28,29).
More information on all of the above functions is provided in the BiomeMD® Patient Manual and you can also find useful information in under "Education".
When things go wrong...
Studies show that a number of factors can alter the composition of the gut microbiota – a state that is commonly termed dysbiosis. Dysbiosis is associated with a reduction in beneficial (SCFA-producing) bacteria and an increase in pathogenic bacteria in the gut. Dysbiosis has been repeatedly been linked to metabolic and inflammatory conditions in humans and mice (35, 36).
Dysbiosis can be caused by (30-34).:
A diet that high in sugar, trans fats, gluten, vegetable oils, food additives, animal fats and processed foods
Medications such as antibiotics, antacids, hormones or anti-inflammatory drugs
Acute or chronic stress
Insomnia or sleep disturbances
Acute or chronic illness
Toxins such as environmental pollutants, pesticides, plastics and cosmetics
Poor living conditions
Chronic states of dysbiosis can lead to damage of the mucus layer and tight junctions, therefore resulting in gaps between enterocytes. These gaps allow the passage of antigens from the gut lumen into the circulation, a process commonly termed leaky gut. When antigens cross the gut wall they have the capacity to over-activate immune cells and produce a pro-inflammatory response which results in further damage to the gut wall. Prolonged over-stimulation of the immune system can lead to systemic inflammation, which has been linked to number of metabolic conditions, such as obesity and insulin resistance, as well as inflammatory conditions such as autoimmune diseases and allergies (37-43)
Inflammation, Ageing and Metabolic Disorders
Systemic inflammation is now recognised as a key driver of metabolic and inflammatory disorders. It is also both the cause and consequence of ageing - connection termed inflammageing. Inflammation causes cumulative oxidative stress and cellular damage making it more difficult for the cells to perform its function. Studies show that systemic inflammation is also associated with inflammation in adipose tissue and brain matter, where it impairs fat loss and neurological function respectively (44).
Inflammation within adipose tissue leads to insulin resistance and fat gain. It also changes the function and hormonal output of fats cells. Normally, as fat cells enlarge, they secrete a hormone called leptin which sends signals of fullness to the brain and reduces food intake. When adipose tissue becomes inflamed, leptin signals are altered and eventually stop being detected by the brain. This is why some people report that they never feel satisfied or that they have no “off-switch” when it comes to food, despite carrying excess weight (45-46).
Inflammation in the brain, known as neuroinflammation, can affect certain areas in the brain that are responsible for decision making, emotional control and impulse management - functions that are crucial for achieving optimal health (47-53).
The hypothalamus is an area of the brain involved in appetite control, energy balance and the stress response. Hypothalamic inflammation impairs our ability to manage stress or detect signals of fullness. This results in increased hunger and food intake, and a reduction in energy expenditure (54-58).
The corticolimbic system includes areas of the brain that are involved in cognitive function, learning, emotional control and the stress response (to name a few). When these areas are altered, our ability to manage stress, employ cognitive restraint and overcome urges is impaired (59-61).
In addition, neuroinflammation alters the production of neurotransmitters responsible for mood, sleep and appetite. It also impairs neurogenesis, the process by which our brain remodels to form new neural pathways (61). This is important when it comes to developing and maintaining new behaviours and lifestyle patterns conducive with health and weight management. If neurogenesis is impaired it is difficult, if not impossible, to develop new behaviours and sustain them long-term.
BiomeMD® protocol aims to restore a healthy microbial diversity, reduce systemic inflammation and support the physiological processes responsible for health and longevity. (more information about BiomeMD®)
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