Over the last 10 years there has been an explosion of research into the gut microbiota and its impact on weight. It has been demonstrated that alterations in the gut microbiota are associated with metabolic disorders such as obesity and insulin resistance, both of which are known to be caused by inflammation in the body. The gut microbiota is responsible for regulating immune function as well as influencing several key processes involved in energy balance and weight management (1-4).
The gut microbiota is made of two main bacterial families (Firmicutes and Bacteroidetes) as well as several smaller families. In a healthy gut, these families are maintained within specific proportions relative to each other and far out-number bacteria that are potentially harmful to the body.
Genes, diet and environment play a part in weight management, with diet and environment being modifiable factors that have the ability to significantly alter the composition of our gut microbiota, either to our benefit or detriment. Stress, medications and a diet high in refined sugar and processed food can lead to dysbiosis, a state of altered gut bacteria which has been associated with a range of metabolic disorders, including obesity (1, 5, 6).
The mechanisms by which dysbiosis can lead to weight gain are:
1. Increased extraction of calories from food
Certain gut bacteria are able to extract more calories from food. Some studies have shown that obese individuals tend to have a higher number of Firmicutes species compared to Bacteroidetes species. Firmicutes is able to extract up to 15% more calories from food than Bacteroidetes. Therefore, two people given the same diet with the same number of calories may have different outcomes when it comes to weight loss simply due to differences in their gut bacteria. (1, 4)
2. Inflammation and altered appetite regulation.
Inflammation plays a large rolein the development of obesity, and the gut microbiota is a key regulator of immune tolerance.
In dysbiosis there is an increase in pathogenic bacteria and with this comes an increase in a specific microbial component called lipopolysaccharide (LPS). This is a highly pro-inflammatory molecule that has repeatedly been associated with inflammation in the body. LPS activates an inflammatory cascade that ultimately leads to the accumulation of inflammatory mediators (immune cells and cytokines) in fat cells and brain matter. This inflammation then alters the function of fat cells and neurons.
Fat cells, or adipocytes, play a role in appetite regulation and energy balance through the release of a hormone called Leptin. Leptin is secreted from fat cells proportionally to the size of the cell. It sends signals of fullness to the brain, which in turn results in a reduction in food intake. The effect of LPS on leptin is two-fold. Firstly, LPS-driven inflammation in adipocytes has been shown to disrupt leptin release, therefore reducing signals of fullness to the brain. Secondly, LPS-driven inflammation in the brain has been shown to reduce sensitivity to leptin, therefore signals of fullness are no longer detected by neurons. These two mechanisms can lead to over-eating and weight gain.
3. Mitochondrial dysfunction and metabolism.
The gut microbiota communicates with our mitochondria, the powerhouse of our cells. This occurs mainly through the action of butyrate, a short-chain fatty acid (SCFA) which is produced by certain species of gut bacteria.
Mitochondria convert glucose, amino acids and fats into energy that supplies our cells and butyrate can help regulate certain steps in this process. The energy produced is then used by the cell to perform its function. In adipocytes, for example, this function includes the release of stored fat.
Butyrate also helps regenerate new mitochondria and clear out by-products that are released during energy production. These by-products, commonly termed free radicals, have the potential to damage mitochondria and therefore reduce cellular energy.
Another mechanism by which gut microbiota modify mitochondrial function is by regulating the availability of nutrients such as B-group vitamins, magnesium and zinc. These nutrients are essential for all mitochondrial reactions.
In dysbiosis, the production of SCFAs is altered and this has been associated with impaired mitochondrial function. When glucose and fats are not utilised effectively, they accumulate in the liver, muscle and adipocytes, usually as fat. With impaired mitochondrial function there is an increase in free radicals within the cell, this results in inflammation that also alters the function of the cell. In adipocytes, inflammation has been associated with reduced leptin signalling and insulin resistance, both of which can lead to an increase in appetite and weight gain.
4. Impaired detoxification
Detoxification is the process by which toxins are converted into safe molecules that are easily eliminated from the body via the gut, kidney, lungs or skin. Each toxin proceeds through two stages of detoxification. The first stage produces a more toxic molecule - a super-toxin - as well as by-products known as free radicals, or oxidants. The second stage converts the super-toxins into a neutral molecule that can be safely eliminated from the body. Free radicals are neutralised by certain nutrients, antioxidants and intracellular enzymes that help mop up these molecules and therefore prevent damage to the cell.(2)
If detoxification is impaired, free radicals and super-toxins accumulate within cells causing inflammation and mitochondrial dysfunction. In addition, toxins are fat-soluble, which means they can easily be stored in fatty tissue where they perpetuate inflammation and prevent the release of stored fat.
Where does the gut microbiota fit in to this?
The liver is the main organ of detoxification, however the gut microbiota plays a key role in the transformation and elimination of toxins before they are absorbed into the blood stream and transported to the liver. Over 800 species of gut microbiota have been found to secrete detoxification enzymes.(5,7,8)One study has shown that the gut microbiota has the ability to transform well over 1000 toxic compounds, including environment pollutants and pharmaceutical drugs, thereby reducing their absorption and impact on the body. (9-11)
In addition, SCFAs produced by gut bacteria have been shown to stimulate the release of detoxification enzymes from gut and liver cells.(12, 13) As mentioned above, SCFAs also play a role in the neutralisation of the free radicals. (14-19)
Another mechanism by which the gut microbiota assist in detoxification is through modulating nutrients that act as co-factors in detoxification reactions, such as B-group vitamins, magnesium, zinc and amino acids. The gut microbiota can influence the absorption of these nutrients and many bacterial species are also able produce various B-group vitamins. (20-22)
In dysbiosis, any or all of these processes can be altered. In addition, certain pathogenic gut bacteria can secrete enzymes that convert toxins into super-toxins. These super-toxins can easily be absorbed into the bloodstream leading to an accumulation of toxins and free radicals in the liver. (23, 24) This perpetuates inflammation and the vicious cycle that hinders weight loss.
5. Altered signalling to the brain
Another mechanism by which the gut microbiota can influence weight management is through their ability to communicate with the brain. This communication can take place through the bloodstream or the Vagus nerve, a nerve that originates in the central nervous system and innervates the entire gut. The Vagus nerve is able to detect changes within the gut wall and lumen and relay this information directly to the brain. This is known as the Gut-Brain connection and research shows that it has a significant impact on brain function.
The gut microbiota communicates with the brain by producing a number of signalling molecules such as SCFAs, vitamins and neurotransmitters and also influencing the release immune mediators. These molecules are mainly detected by the Vagus nerve which transmits signals to the brain. They can also enter the brain via the blood stream. (25, 26)
The neurological functions influenced by gut microbiota that are important in weight management include:
- Protecting the brain matter from toxins and inflammation. (27)
- Influencing the production of neurotransmitters which are responsible for appetite control, mood, motivation and sleep. (28)
- Influencing hormones that are involved in regulating appetite and improving metabolism and energy expenditure. (29-32)
- Assisting neurogenesis, a process that helps build new neurons and therefore helps in the development of new behaviours and habits. (33-37)
In dysbiosis, the altered bacterial composition and presence of more pathogenic gut bacteria results in a reduction in beneficial signalling molecules and an increase in inflammatory signalling molecules, leading to inflammation within the brain matter. This is known as neuroinflammation. Some of the processes that are affected by neuroinflammation include appetite regulation, metabolism, mood, behaviour, stress response and sleep, all of which can result in cravings and weight gain. (38-49)(More detailed information on the Gut-Brain Connection will follow in a separate blog).
Successful weight management is much more complex than eating less and exercising more, which is why traditional diets don’t work. In order to lose weight and successfully maintain a new lower weight long-term, gut function must be restored and the above key processes must be managed.
The Biome Protocol includes supplemental nutrients that support the growth of healthy gut microbiota, as well as nutrients that are known to support the physiological processes involved in weight management. The dietary recommendations are flexible and based on foods that serve a purpose – to feed our gut microbiota and provide nutrients that assist with essential cellular functions. The protocol also provides you with information that will help you safely modify your diet according to your needs on completion of the program.
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