Background to the gut

The gut is a segment of the gastrointestinal tract connecting the stomach to the back passage and consists of two parts: the small intestine and the large intestine. The digestive system itself is a lot bigger. When we ingest our food, the food travels down a series of “roadblocks” essentially, where it goes through various phases of digestion and absorption.

1. The mouth and teeth release salivary enzymes and chew (mastication) the food as the initial point to break the contents down.

2. The oesophagus which is the long tube, transfers the food from the mouth to the stomach.

3. The stomach which secretes acid and peptic enzymes to start breaking up food and killing bacteria on and in the food. It usually takes between 1-5 hours for most moderate size meals to be emptied from the stomach.

4. The small intestine is a narrow tube and where protein, fat and carbohydrate are broken down into amino acids, sugars and fatty acids to be absorbed into the blood stream. This process takes between 2-4 hours.

5. The colon (or large intestine) extracts the salts and water from the remaining food and solidifies it. The bacteria within the colon ferment all the unabsorbed foods into short chain fatty acids (SCFAs) which are used as energy. This process takes between 5-70 hours.

The remainder of the digestive tract consists of the pancreas, liver and gall bladder which basically secrete juices, acids and enzymes to digest remove toxins and help store nutrients.

Gut Health and the microbiome

Gut health isn’t about being vegan, vegetarian or whatever. You cannot fully optimise body composition or even performance if you don’t address the health of your gut.

The gut is an amazing place. It’s a whole planet and ecosystem of life. We essentially are vesicles for the bacteria within our bodies that actually provide us with energy and an ability to digest our food. These bacteria are more commonly known as the “microbiome”. We are home to as many as 1000 distinct bacterial species; the two most common phyla are Firmicutes and Bacteroides which account 70-75% of the microbiome. Up to 75% of the body’s immune system is dictated from the gut. Over 60% of neurotransmitters are produced in the gut that affects focus, sleep and motivation.

The human intestine harbours nearly 100trillion bacteria that are all essential for health and offer functionality towards out gut. Gut health is a prerequisite for sustainable and optimal body composition, immunity, mood, hormones and improved performance.

Disruptions to our microbiome are becoming increasingly associated with increased prevalence of allergies, autoimmune diseases, metabolic disorders and even neuropsychiatric disorders.

A quick note on Inflammation

Inflammation in the body is a good thing. Normal day to day activities can increase inflammation through oxidative stress, production of reactive oxygen species (ROS) NF-kB, NOS amongst others. Normal aerobic metabolism, eating, exercise etc all produces free radicals (as a by-product of energy production using oxygen). Free radicals produced by this, signal the cell to make its own endogenous antioxidants.

In small amounts it triggers activation of Phase 1 and Phase 2 enzymes which are the body’s natural pathways to reduce inflammation. One of the key defences of the body is the NRF2 pathway (nuclear factor erythroid 2-related factor). Phase 1 and phase 2 enzymes are stimulated by both exogenous (through food) and endogenous (body produces) antioxidants. Phase 2 enzymes are regulated by the Antioxidant response element (ARE).

Problem with modern day life

The gut is attacked each day by food, lack of exercise, alcohol, drugs, environmental chemicals and more – a typical Western day world. This can cause an imbalance of the bacterial composition of the gut, which are there to keep things in check, digest and absorb our food and essentially keep us happy and health. With improper gut health, this can lead to excess inflammatory signals which may lead to general digestive issues, systemic inflammation and even mood swings (the second brain).

Inflammation comes from inflammatory signals within the body (self-explanatory).

The inflammatory response has four phases: inflammatory inducers (infection or tissue damage), inflammatory sensors (mast cells and macrophages), inflammatory mediators (cytokines, chemokines, etc.) and the tissues that are affected. Each phase has many options that are triggered based on the type pathogen introduced. We are going to discuss one; LPS.

The bad part of inflammation

Lipopolysaccharide (LPS) is a large molecule found in the outer membrane of gram-negative bacteria. LPS binds to toll like Receptor (TLR-4) and creates a cascade of inflammatory and redox sensitive pathways. Inflammatory cytokines like TNF-a (tumour-necrosis factor), 1L 1b (interleukin), IL-6 and ROS (reactive oxygen species) have damaging effects on the body. Within the gut, excess inflammation can cause digestive distress, irritable bowel disease (IBD), gut dysbiosis and a general irregularity with absorbing vitamins, minerals and even proteins.

NOTE: I’m banging on that all inflammation and oxidative stress is a bad thing. Well it isn’t. You need a level of inflammation and oxidative stress to stimulate body repair and also to improve responsivity to immune signals. Free radicals produced by this small level of inflammation signal the cell to make its own endogenous antioxidants.

Alongside this inflammation, is a disturbed intestinal barrier. This barrier gets damaged and increases the permeability of it, which can cause “leaky gut”. This goes in conjunction with a decrease in activity of brake signals such as short chain fatty acids (SCFAs), PPAR-alpha, and AMPK that act as anti-inflammatories and protect intestinal barrier function. This constant low level systemic inflammation can precede insulin/leptin resistance, obesity, mental health problems, increased body fat, and overall poor health. This is all down to the bacteria that live in our gut being damaged and destroyed by modern day life.

High level inflammation is a chronic disease! Intestinal permeability is associated with problems such as IBD, SIBO and bacterial overgrowth. These are caused by impairments to the gut mucosal barrier which would normally prevent harmful toxins and microorganisms from entering the body.

Fiber

Fiber is part of the carbohydrates that you eat. Whilst carbohydrates provide energy, they are also important in creating various types of fiber. Fiber can help to stimulate the intestinal microflora and provide specific functions to the body.

• It helps to create energy through lactose digestion and the ability to produce short-chain fatty acids

• Modulates cell growth and differentiation within the gut

• Is defensive against pathogens

• Stimulates the immune system

• Provides natural immunity against infections

• Produces vitamins and reduces blood lipids

• Hydrolyses insoluble fibers (IF) to produce bioactive polyphenolic compounds

There are three main types of fiber: soluble fiber, insoluble fiber (IF) and resistant starches (RS).

Soluble fibers mix with water and form masses that get fermented (almost fully) by colonic microorganisms. This increases the bacterial content and adds weight to stool.

Insoluble fiber do not mix well with water and gets fermented by the colonic microorganisms to form short chain fatty acids (SCFAs: (acetate, propionate and butyrate)). SCFAs provide between 5-10% of the energy production in humans and also help secrete satiety inducing hormones (leptin and peptide YY). SCFAs are key to activating immune and inflammatory responses which is the main thing that will be touched on within this section.

NOTE: SCFAs are the preferred respiratory fuel to the colonocytes. In other words it helps these cells fulfil their functions correctly. The main one is butyrate, and this plays a key role in DNA stabilisation and repair whilst also functioning as a HDAC inhibitor (performs anti-inflammatory functions by supressing activity of specific immune cells). Butyrate helps to maintain the integrity of the bowel well (epithelial defence barrier) and overall, maintains a healthy gut. It promotes the growth of villi, microscopic finger-like extrusions that line the intestines, and enhances the production of mucin, a gel-like substance that coats the inside of the gut

Now, IF does also have negatives as it speeds up the transition of food through the gastrointestinal tract (GI) which reduces absorption. This is bad for our vitamins and minerals, but good for keeping blood glucose levels stable as glucose is one of the main nutrients that gets passed through quickly.

Resistant starch (RS) are molecules which carry a lower caloric amount compared to other fibers. There are three types which have different roles within the body, but these won’t be explained here (RS1, RS2 and RS3). About 30-70% of RS is fermented by colonic microorganisms to produce SCFAs whilst the rest is excreted in stool (therefore adding bulk).

Probiotics

Probiotics are live microorganisms that are administered through dietary supplements or as food products (like yoghurt). Several probiotic bacteria have been tested for health benefits including Lactobacillus sp (firmicutes) and Bifidobacterium sp (actinobacteria).

Probiotics work by providing multiple strains of various bacteria that work through cross feeding. Cross feeding is when one bacterial species produces metabolites that others around it use for fuel. Your probiotics that you get from foods or drinks can help to prevent leaky gut consequences and restore the colonization of healthy gut bacteria. All these combined will contribute to repairing and preventing “leaky gut”.

Now, no probiotic on its own works effectively, but if you take them in a stack, they can complement each other on their ability to improve digestion. However, when looking for a probiotic, make sure that they fulfil the following criteria:

1. The bacteria strains must be able to survive the stomach acid and bile so they reach the intestines alive in adequate numbers.

2. Bacteria strains must have health promoting features (and not just added because they sound good).

3. The probiotic must be guaranteed to survive through the storage period and shelf life of the product.

Generally most people respond well to the Lactobacillus family of friendly probiotic material.

Prebiotics

Prebiotics are “colonic food” – “a food that enters the colon to become a substrate for endogenous bacteria and indirectly provides the host with energy and metabolic substrates”. The carbohydrates that we consume (in various ways) are able to stimulate the growth of beneficial bacteria at the expense of the pathogens which are harmful to us.

A prebiotic is classified into one of three things.

1. Resistant to digestion and absorption in the upper GI tract (stomach and small intestine)

2. Can be fermented by the microbiota in the colon (intestine)

3. Can selectively stimulate the growth of beneficial bacteria within the gut (Bacteria such as bifidobacteria and lactobacilli)

Indigested carbohydrates such as oligofructose and inulin have the best beneficial effects on the body because they preferentially stimulate the growth of the “good” bacteria that we always hear about. As well as this, they have numerous other health effects:

1. They help to normalise stool frequency and consistency. On the other hand, prebiotics can also increase flatulence. This is due to the “extra feeding” and fermentation of the gut microbiome and the gases that they produce as a result. Yep, you fart the farts of bacteria

2. Potent antioxidant effects, specifically from arabinoxylans (ABX) that contain ferulic acid. These have benefits to reducing the risk of atherosclerosis and coronary heart disease (CHD)

3. Prebiotics have been shown to stimulate natural killer cells and increase the ability of SCFAs to provide anti-inflammatory responses.

4. Some studies have shown that prebiotics like ABX reduce levels of B-glucoronidase in the colon. B-glucoronidase is a nasty compound that when it is hydrolysed, produces toxic compounds in the colon and can lead to the formation of cancer cells. Less b-glucoronidase is a good thing.

5. Lastly, prebiotics can reduce levels of triglycerides and cholesterol in the body. High levels of these two are associated with increased risk of cardiovascular disease. However, prebiotics have an ability to “mop up” excess levels of serum cholesterol and triglycerides.

Effect on Body

I mentioned before that inflammation can lead to insulin and leptin resistance. But how does it do this? Well, let’s explore some technical jargon on how it does. Data in mouse studies shows that germ free mice

Without gut bacteria, our endothelial lining is more permeable to inflammatory lipopolysaccharides (LPS). An increase in LPS causes a chronic inflammatory cascade that reduces short chain fatty acid (SCFA) production from the coloncytes (the cells that line the colon).

An increase in LPS incudes a chronic inflammatory process that reduces SCFA production from the colonocytes. This reduces SCFA biosynthesis and eicosanoid production which facilitates lipid biosynthesis and fat accumulation. So, how can an imbalance of bacteria cause insulin and leptin resistance?

Increased LPS facilitates lipid biosynthesis and fat accumulation, increasing overall production of insulin and negatively regulating normal signalling through the insulin receptor/IRS-1 axi. What’s more, elevated levels of inflammation also affect hunger and satiety hormones such as glucagon-like peptide-1 and peptide YY, decreasing satiety upon food intake leading to weight gain. The decreased satiety hormones affect the way that leptin works. Leptin tells us when we are hungry, but if we still feel “full” from the last meal, then leptin doesn’t work and we end up with leptin resistance. Insulin resistance comes from an increase in weight gain. In less fancy terms:

Less gut bacteria -> Increased inflammation -> Don’t feel full when eating -> Over eat -> More insulin being pumped out -> Leptin resistance -> Weight gain -> Insulin resistance

Now with less digestion or faster gastric emptying this can also significantly reduce vitamin and mineral profiles of the body. Ensuring that you have optimal levels of gut microbiota will improve the absorption of calcium, magnesium and other trade minerals. Not only this, but the gut can also produce vitamins B and K. Strains of the lactobacillus are able to promote bifidiobacteria biosynthesis of B vitamins and vitamin K.

Now if you’re a woman who has some problems with your hormones, then this next paragraph is for you. Gut microflora will aid with estrogen management. It does this by reducing the levels of b-glucoronidase (this is the enzyme that prevents proper elimination of estrogen). With gut dysbiosis (low microbial diversity), this can cause a reduction in circulating estrogens and the potential development of: obesity and metabolic syndrome, cardiovascular disease and cognitive function. What’s more, the gut microflora is exceptionally important for the absorption and proper functioning of phytoestrogens, lignans and flavonoids which are all important in estrogen metabolism.

Lack of macronutrient digestion

Digestion of protein is completed in the small intestine by the pancreatic enzymes trypsin, chymotrypsin, and carboxypeptidase.

Depending on the type, carbohydrates are broken down into monosaccharides for absorption. Now these compounds are digested by specific enzymes in the microvillus membrane (brush border of the intestine).

Enzymes break down fat into fatty acids and glycerol. In the small intestine bile breaks down fat into small droplets that are easier for the lipase enzyme to work on.

The balance of enzymes within the gut are very particular and they require their own little “habitat” to work in. If that habitat is off balance, the microvilli, enzymes and bacteria within stop functioning.

Effect on Performance

I have touched on a few points above on how gut dysbiosis and inflammation can affect the body, but now we can delve a little deeper into how. Excess LPS production speeds up intestinal motility (the speed at which food passes through the digestive system). Imagine you are driving down the road at 1mph and you have to post letters from your car window into a basket on the road at each house. Driving at 1mph you would have chance to post most, if not all the letters. Now speed that up to 30mph, and you don’t have a lot of time to post your letters. This is the same with the gut. The less time the food stays in the system for, the less time the endothelia and microvilli within the gut have to absorb the nutrients from the food you are eating. Imagine that you aren’t able to absorb the protein and amino acids form your food – this can have a seriously negative impact on performance and muscle building.

A less efficient absorption of protein and nitrogen reduces the potential for muscle building. Nitrogen is needed for tissue protein synthesis and the body must be in a positive state in order to repair and build new muscle. Even if dietary intake of protein is high, if the gut bacteria in the intestinal lumen are not sufficient enough to break these down into amino acids, then nitrogen balance is reduced. What this does is ultimately causes a negative anabolic effect and increased catabolic effect on the muscles.

The increase in LPS also causes more cortisol to be released from the adrenals. Too much cortisol can have a negative impact on muscular performance and growth, and even cause atrophy due to IGF-1 and insulin signals being blunted through down-regulation of mTOR pathways.

Remember that Leaky Gut I explained further up, well here is where is has a massive negative effect on performance. Excess LPS in fat tissue leads to an activation of PPAR-gamma and in turn, this upregulates triglyceride synthesis and fat storage. Alongside this, LPS will activate TLR-4 (TLR-4 is involved in pro-inflammatory cascade) releasing more inflammatory signals and causing insulin INSENSITIVITY in muscle. Instead of insulin being anabolic in a lifter, it instead becomes catabolic.

LPS = TLR4 = reduced insulin sensitivity (or insulin resistance) = fat accumulation.

Two things can now happen. A – you get that skinny fat look, or B - it is difficult for you to gain muscle due to the reduced insulin response in the muscles.

Gut Brain Axis

The gut and its microbiome are basically an endocrine organ – by controlling and influencing the entire body and the brain. The human gut harbours a dynamic and complex microbial ecosystem, consisting of approximately 1 kg of bacteria in the average adult, approximately the weight of the human brain. The gut and brain work in tandem, each influencing one another on mood and satiety signalling. These signals are connected during fetal development via the vagus nerve; one from the central nervous system and the other through the enteric nervous system.

A healthy gut means a healthy brain. This seems simple, but now neuroscientists have found pathways of communication between the autonomic nervous system and the enteric nervous system; establishing direct communicative link between our gut and our brain. This is more commonly called the Gut-Brain Axis. What this means is, that if we have a healthy gut, we are also more likely to have a healthier brain, less prone to mood swings, depression and anxiety. The Gut-Brain Axis is a cross talk (albeit a very, very complex one) between the endocrine system (hypothalamic-pituitary-adrenal axis (HPA), immune (cytokine and chemokine) and the autonomic nervous system (ANS).

Our microbiome interacts with the gut-brain axis through several different pathways.

1. The vagus nerve

2. Neuroendocrine signalling

3. Tryptophan signalling. Now this one is key for mood disorders. Nearly 95% of serotonin (5-HT) is produced by the muscosal enterochromaffin cells.

4. Immune system

5. Production of microbial metabolites. Many species of Lactobacillus and Bifidobacterium produce gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the brain. In addition, Candida, Escherichia, and Enterococcus produce the neurotransmitter serotonin, while some Bacillus species have been shown to produce dopamine

The HPA is responsible for the processes in response to psychological and physical stressors. In response to stress corticotrophin-releasing factor (CRF) is released and induces adrenocorticotrophic hormone (ACTH). This then secretes cortisol from the adrenal into the system and as we know, cortisol is the ultimate stress hormone of the human body.

A direct link between the HPA and the gut microbiota has been established via the ENS (enteric nervous system). The microbiota can directly affect functionality of neuronal activation of stress circuits. When we are exposed to stress, our gut can actually activate immune responses. However, when the gut microbiota isn’t working properly, there is over activation of the HPA axis which chronically elevates cortisol levels. Elevated HPA levels have been linked with anxiety, depression and a compromised immune system.

This means that our intestinal microbiome plays a vital role in controlling aspects of our neurobiology including mental health, behavioural health, memory, depression, mood, anxiety and even food preferences. Now, the exact way in which our microbiome affects this neurobiology isn’t well defined however evidence suggests that the dopamine and serotonin produced by gut microbiota do play a role. Ever get that knot in your stomach? Big decisions ahead and you get that “gut feeling”; well it’s actually a real thing. Our gut is our second brain and certain strains of bacteria can increase our anxiety. Next time you get that feeling, stop and think for a second about what your gut bacteria are telling you (but also make sure that you aren’t just hungry first).

Common Causes

Common causes of a leaky gut are nutrient deficiencies (l-glutamine, zinc and vitamin A), stress (big one) and medications, such as antibiotics. The following symptoms are all signs that unhealthy bacteria have taken over too much space in your gut, and you probably need to address aspects of your diet and lifestyle to help heal your gut.

1. Gas and bloating

2. Constipation or diarrhoea

3. Fatigue

4. Nausea

5. Headaches

6. Sugar cravings and cravings for refined carbohydrates

How to optimise your gut microflora

Well firstly, it is to introduce some healthy prebiotics, probiotics and some fiber that has been mentioned before.

Remember a microbial imbalance (or dysbiosis); food or environmental triggers can cause intestinal hyperpermability. The barrier normally prevents harmful toxins and microorganisms from entering the body. Compromises in this barrier can cause chronic inflammation. Now, certain things need to be avoided or reduced in order to get the whole benefits of the gut and its diversity.

Interventions

1. Removing any FODMAP– excess fat, alcohol, stress, allergens, sensitivities and problematic GI microbes.

2. Replace dietary fibre to support gut transit time and motility and replace the factors necessary to optimise digestive secretions. Zinc is a crucial cofactor in hydrochloric acid synthase.

3. Repopulate the gut with the use of probiotic foods to bring the microflora back into balance and prebiotic foods to help the commensal bacteria to proliferate. a. Probiotic foods – yoghurt, kefir, sauerkraut.

4. Repair the lining of the gut to optimise absorption and immune tolerance. This requires eating foods rich in zinc, vitamins A, D, and C and amino acids particularly L-glutamine.

So how do you follow these interventions? To make this easier for you, I have a list of some great foods and supplements that you can take to help your gut, all of course backed by science.

Supplements

Glutamine

Glutamine plays a crucial role in providing fuel for enterocytes, renal epithelial cells and immune cells. It is used when immune cells divide, promoting B-cell differentiation, cytokine production and neutrophil superoxide (free-radical scavenger). The gut is the primary site for glutamine metabolism and mediates the parts of the protective nature of the gastrointestinal tract; being an important component in maintaining gut mucosal integrity. Prolonged physical and mental stress causes the glutamine pool to drop and leads to mucosal cell atrophy. It may therefore be necessary to supplement with oral glutamine tablets to support GI mucosal growth (Neu and DeMarco, 2002)

Ginger

Ginger is a lovely and diverse spice to use. A recent study by Teng isolated the exosome-like nanoparticles (ELNs) from ginger and found them to help prevent alcohol-induced liver damage and artificially induced colitis. The ginger derived exosome-like nanoparticles (GELNs) were preferentially taken up by the Lactobacillus gut bacteria (the healthy and good one) and actually boosted their numbers. Many studies can outline correlations between dietary interventions and changes in the microbiome, but Teng’s work was one of the first to identify specific molecular mechanisms that were involved. There are more herbs and plants that are being examined in this way that can help repopulate the gut microbiome (Y. Teng 2018).

Selenium

Selenium is well known to have anti-oxidative and anti-inflammatory properties, and more recently has been investigated for its effects on the gut including modulation of inflammatory pathways often associated with IBD and IBS. Whilst selenium deficiency is rare, people with IBS will struggle to absorb certain nutrients from their diet, and may lead to deficiency which in turn will reduce immunity in the body. Deficiency symptoms include chronic fatigue, associated with hypothyroidism as selenium helps convert the inactive from of thyroid hormone, T4 into the active form of T3.

The diversity of the gut microbiome is important to regulate normal bowel movements, absorption and immunity; lesser diversity is associated with inflammatory diseases. Studies in mice have shown that dietary Selenium (sodium selenite) increase gut microbiome diversity and therefore had positive effects on the immune response (Kasaikina et al., 2011).

Foods

Probiotics are found in fermented foods, as well as in some supplements. And prebiotics are found in certain fruits, vegetables, and whole grains. The most central prebiotic of all is fiber

• Various pickled fermentations of cabbage sauerkraut, turnips, cucumbers, onions, squash, and carrots. All of these are high in antioxidants, good gut bacteria and probiotics which all support your intestinal microbiome.

• Kefir is probably one of the most probiotic rich foods on the planet. Now make sure that when you buy your kefir, it is not a general commercial version. These versions typically don’t have the live cultures that you need and can be filled with sugar which actually feed the pathogenic bacteria instead.

• A study showed that kefir could restore the natural balance of four different bacteria in the gut and even promote health of an enzyme in the brain which is required for normal nervous system function. Which means that kefir is great for the gut, and the brain – and therefore the gut-brain axis (Experimental Biology 2018).

• Tempeh (a fermented soy food). A recent study in the Journal of Microbiology showed that using tempeh increased healthy bacteria such as Lactobacillus (Kuligowski 2013)

• Kimchi is a spicy alternative to sauerkraut. A 2014 study published in the Journal of Medicinal Food showed that kimchi is high in probiotics which as you now know, is excellent for gut health (Park 2014).

References

Experimental Biology 2018. "Drinking kefir may prompt brain-gut communication to lower blood pressure: Long-term probiotic use balances gut microbiota, brain chemicals in rodent study." ScienceDaily

Kuligowski, M., Jasinska-Kuligowska, I. Nowak, J. 2013. Evaluation of bean and soy tempeh influence on intestinal bacteria and estmation of antibacterial properties of bean tempeh. Pol J Microbiol. 62(2): 189 – 94.

Kasaikina, M., Kravtsova, M., Lee, B., Seravalli, J, et al. 2011. Dietary selenium affects host selenoproteome expression by influencing the gut microbiota. FASEB. 25(7): 2492-9.

Neu, J., Demarco V, Li, N. 2002. Glutamine: clinical applications and mechanisms of action. Cur Opin Clin Nutr Metab Care. 5(1): 69-75.

Park, KY., Jeong, JK., Lee, YE., Daily, J. 2014. Health benefits of kimchi (Korean fermented vegetables), as a probiotic food. J Med Food. 17(1): 6-20.

Teng, Y. 2018. Plant-derived exosomal microRNAs shape the gut microbiota. Cell Host Microbe. 24: 637-52.