gut health in practice v2 - the-nutrition-network.com

Education Series

Gut Health in Practice

Professional Supplement Specialists

INFORMATION FOR PROFESSIONAL USE ONLYbiocare.co.uk

IntroductionMore than 2000 years ago, Hippocrates said “all disease begins in the gut”1. But only now are we beginning to understand how the gastrointestinal (GI) system is involved in the development of disease. Studies over the past two decades have shown that in addition to GI diseases, an unhealthy gut can contribute to a wide range of diseases including obesity, diabetes, autoimmune disorders, hormonal imbalances, chronic fatigue, autism and depression, as well as cardiovascular disease and rheumatism.

The statistics of GI disease paint a bleak picture. Almost 2 million people in the UK were diagnosed with a digestive disorder in 2005/062 and 60-70 million Americans have been officially diagnosed with a digestive disease3. One third of the UK population regularly suffers from digestive illnesses such as irritable bowel syndrome (IBS), constipation, diarrhoea, stomach-aches and nausea4. To put this in perspective, over 3.7 million operations were carried out on parts of the digestive tract in the UK in 2005/065 and GPs prescribed gastrointestinal drugs costing more than £562 million last year in England6. Clearly, GI disease is a huge burden on the UK healthcare system and on the quality of life of millions of people.

The human gut is exposed to many challenges. In this paper we’re going to look at these challenges and pick apart why the gut is the root of many diseases and see if we can find some solutions to the most common gut issues with which many are faced.

A Model of Gut HealthThere are four central elements that underpin the gastrointestinal system – digestion & absorption, integrity & immunity, motility, and the microflora. The interplay between these components influences overall health and the risk of disease. If one or more of these isn’t functioning optimally, it can have repercussions for the whole GI tract.

Digestion and absorption are the most fundamental aspects of gut function and the processes which allow our body to digest and absorb nutrients from food. Many of the chemicals produced in the digestive

tract serve other purposes too, for example stomach acid acts as an antimicrobial to defend against foreign invaders and bile acids act as a vessel for the excretion of ‘spent’ hormone metabolites.

Integrity and immunity encompass the structural and the immunological regulation that occurs in and around the gut. Our digestive system may determine our immune function, glandular activity and neurological function7. The GI tract is the largest interface that we have with our external environment. It manages exposure to foods, microorganisms, toxins and other substances, meaning its integrity is profoundly important.

Motility involves the movement of foods throughout the digestive tract which is regulated by a host of complex processes. The gut is the largest endocrine gland8 and the intestine is the largest immunological organ in the body9. It is home to the enteric nervous system, which is almost like a second brain, using more than 30 neurotransmitters. It produces 95% of the serotonin produced in the body, which is critical to motility.

Finally the GI tract harbours trillions of microorganisms10 which govern immunity, modulate risk of allergy, produce chemicals associated with heart attack and stroke prediction11, and might even guide the workings of our mind12.

Gut DysfunctionGI disorders can be separated into different categories – functional, structural and immunological.

Functional disorders such as IBS are well-categorised but poorly understood as they are often multifactorial in causation and difficult to treat. They usually arise from a combination of underlying factors including maldigestion, dysbiosis, poor motility, food sensitivities and diet.

Structural disorders include intestinal hyper-permeability and diverticular disease. These conditions are characterised by a physical change in tissue structure and often inflammation is a common denominator. Structural disorders share comorbidities with other conditions, for example intestinal permeability is common in coeliac disease.

Immunological conditions such as inflammatory bowel disease (IBD) and coeliac disease arise as a result of autoimmunity, whereby an antigen is presented to the gut interface and the immune system reacts by attacking the antigen and body tissues with similar protein sequences, resulting in damage to peripheral tissues.

All three categories of disease are influenced by the central elements and it seems that a number of common processes underpin the pathogenesis of many of these diseases, including suboptimal integrity, inflammation, immune dysfunction, dysbiosis and malabsorption. Throughout this paper we will look at the complex interplay between these central elements and gut dysfunction, and, most importantly, how we can treat some of these conditions.

INFORMATION FOR PROFESSIONAL USE ONLYbiocare.co.uk 2

FunctionalIBS

BloatingAbdominal pain

StructuralIntestinal

hyper-permeabilityDiverticular diseasePolyps and cancer

Immunological IBD

Coeliac disease

Digestion &

Absorption

MotilityIntegrity & Immunity

Microflora

An Overview of DigestionHealthy digestive function is critical to optimum health and is usually the first port of call in any treatment regime. Dramatic improvements can be made to someone’s wellbeing simply by improving their digestive potential.

Digestion involves the mechanical and chemical breakdown of food into smaller components that can be more easily absorbed and assimilated by the body. A host of digestive organs work in harmony (including the digestive tract, pancreas, liver and gallbladder) to ensure that we are able to extract the nutrients from food to power demands of the body, in order to remain healthy. But this is just the beginning; the digestive process also regulates aspects of immunity, inflammation and detoxification.

Once food has been efficiently digested, it needs to be absorbed into systemic circulation. Poorly absorbed nutrients may impact on enzyme and other biochemical pathways e.g. diminished methylation due to lack of vitamin B1213. In the next section we’re going to look at why the upper digestive tract is paramount for digestion, protection of the lower gut and for general health.

The Upper Digestive TractFood is a challenge to the digestive system. Fortunately the gut is highly adapted to digest a huge variety of foods. However some foods contain substances that may present a systemic immunological or inflammatory challenge that isn’t only limited to the gut.

So why is the upper gastrointestinal tract so important? Well, principally because it is where most chemical digestion takes place. It consists of the oesophagus, stomach, and the upper duodenum. Digestion begins in the mouth, mostly via mechanical breakdown of foods by the teeth, but this is also where saliva lubricates and moistens food, and amylase enzyme initiates breakdown of polysaccharides. The release of saliva in conjunction with parasympathetic nervous stimulation ensures secretion of digestive juices and hydrochloric acid in the stomach. The mouth also contains epithelial growth factor which complexes with thiocyanates in food to stimulate epithelial tissue repair14. Nitrate-converting bacteria in the mouth stimulate nitric oxide production and vasodilation15. The age old saying of “chew your food properly” can certainly support effective digestion.

The StomachThe stomach is often referred to as the most vital part of the digestive system16. At the simplest level it is a holding and mixing tank for the food and drink we consume, but there are also functional properties of the stomach such as chelation of inorganic minerals, digestion of proteins by pepsin, and secretion of digestive enzymes, stomach acid and intrinsic factor (a compound required for vitamin B12 absorption). Stomach acid acts as an acidic barrier to pathogenic bacteria and also regulates the population and composition of lower intestinal bacteria17. One of the most common stomach-related issues is acid reflux and gastro-oesophageal reflux disease (GERD).

Clinical Focus: Acid Reflux & GERDThe prevalence of acid reflux is on the rise. Whether it is triggered by a glass of red wine or spicy food, it causes a great deal of discomfort to sufferers. Gastro-oesophageal reflux disease (GERD) is a digestive disorder that affects the lower oesophageal sphincter resulting in acid reflux and ‘heartburn’.

However, the genuine pathophysiology of this disease is poorly understood and most research has focused on the best treatment to reduce symptoms. The most well-known and prescribed treatments include proton pump inhibitors (PPIs) and antacids, which block and neutralise stomach acid respectively. Unfortunately, as one of the primary functions of hydrochloric acid is to act as a barrier to pathogenic organisms, the long term use of these medications can increase the risk of H pylori infection.

Too little stomach acid and prevalence of H pylori may actually be the root cause. Dr. Jonathan Wright MD confirms that supplementing with HCl and pepsin often relieves the symptoms of heartburn and improves digestion, at least in people who have hypochlorhydria (low stomach acid)18. Low HCl results in fermentation of carbohydrates increasing hydrogen gas and pressure in the stomach, forcing undigested food back up towards the oesophagus and exposing unprotected tissues to the harmful effects of hydrochloric acid. Damaged tissues in the stomach and oesophagus cause the release of inflammatory cytokines that attract inflammatory molecules like interleukin-8, interleukin-6, and others19.

Elevated hydrogen increases H pylori and other pathogenic organisms20. H pylori suppresses gastric acid secretion, thus compounding the problem21. Furthermore a number of drugs can relax the lower oesophageal sphincter including calcium channel blockers, NSAIDs, SSRIs, corticosteroids and nitrates. Discontinuing PPIs can cause rebound hypersecretion of acid22.

StomachHCl Acid & PepsinProtein digestionSterilisation Preparation of B12 & Minerals

Large Intestine Water absorptionWaste disposalBacteria support digestion

GERD



MouthChewing & saliva

Digestion of starches Stimulate

digestion & kill bacteria

StomachHCl Acid & PepsinProtein digestion

Sterilisation Preparation of B12

& Minerals

Large Intestine Water absorption

Waste disposalBacteria support

Digestion

FoodProtein/Carbohydrate/Fat

Micronutrients – Vitamins & Minerals

Viruses/Bacteria/Toxins

DuodenumPancreas

secretes protein, fat and carb

digesting enzymesLiver secretes bile

Jejunum/IleumAbsorption of

nutrients

Low stomach acid

Bacterial Overgrowth

Increased Intra-Abdominal

Pressure

GERD

Undigested Carbohydrate

Nutritional Support for Acid RefluxThe first stage of any protocol for acid reflux is to remove underlying causative factors such as junk food, high carbohydrate diets (diet reduces symptoms as effectively as PPIs23), trigger foods (alcohol, caffeine, spicy food, chocolate) and to address lifestyle factors such as stress, weight, physical activity and smoking.

The next stage is to calm inflamed tissue and support the repair process:

• �Slippery�elm mucilage soothes the throat and lining of the stomach, and stimulates mucus secretion24.

• �Gamma� oryzanol from rice bran oil normalises vagus nerve stimulation of gastrin25, has potent antioxidant activity and has an anti-ulcerative action on gastric lesions26.

• �Marshmallow soothes irritated mucous membranes and has been used as a remedy for ulcers27.

• �Cabbage/cabagin has traditionally been used to support the healing of peptic ulcers28 29.

• �Deglycyrrhizinated�licorice increases mucin production30 and exhibits activity against H.pylori31 32.

• �Aloe�vera has a long tradition of use for its wound healing and anti-inflammatory properties33.

• �Zinc34 and vitamin� A35 regulate mucosal integrity and protect against peptic acid injury.

Then tackle underlying dysbiosis and support connective tissue repair:

• �Probiotics inhibit the growth of H. pylori36 and improve effectiveness of antibiotic treatment37.

• Garlic�extracts are also effective against H. pylori38.

• �Cinnamon has antibacterial properties including against H. pylori39 and reduces gastric ulcers40.

• �Mucopolysacharrides� and glucosamine support synthesis of glycosaminoglycans which support connective tissue synthesis in the stomach.

Finally, promote effective digestion and provide additional nutrient support:

• �HCl�& pepsin and digestive�enzymes normalise digestive function once healed.

• �Multinutrient/mineral�complex if on PPIs due to issues with malabsorption.

The Small Intestine and Digestive OrgansThe bulk of chemical digestion happens in the duodenum, supported by the peripheral digestive organs such as the liver, gall bladder and pancreas, which secrete bile and digestive enzymes. As we age, output of digestive enzymes decreases41, meaning our digestive capacity also decreases, resulting in undigested foods passing through to the large intestine.

These foods are often fermented by the microflora and can lead to a buildup of gas, causing symptoms such as flatulence, bloating and belching. Certain digestive enzymes such as lactase are often produced only in very small amounts in non-Caucasians and therefore consumption of dairy containing lactose can result in a number of gastrointestinal symptoms, known as lactose intolerance.

Frequent stimulation of the pancreas and gall bladder via high refined carbohydrate and sugar diets can lead to pancreatitis42 and gallstones43, which also reduce digestive capacity, but more importantly are risk factors for the development of pancreatic cancer44. Therefore balancing blood glucose is paramount when considering digestive capacity.

AbsorptionAfter the complex digestive process of breaking foods into smaller particles, nutrients need to be absorbed across the intestine into the circulation. Most nutrient absorption occurs in the jejunum, the central area of the small intestine. The specialised cell layer of the small intestine lining is usually only one cell thick, an advantageous adaptation to allow a shorter diffusion path of nutrients into the blood stream. It also contains circular folds, villi and microvilli to increase the surface area of the intestines for effective absorption and also support the motility of food through the small intestine. Malabsorption can lead to a plethora of negative health outcomes including bloating and flatulence (common symptoms of lactose intolerance), anaemia (B12, folic acid and iron deficiency), muscle cramps (vitamin D and calcium deficiency) and weight loss (macronutrient deficiency).

Malabsorption can occur as a result of mucosal damage, pancreatic insufficiency, impaired circulation and defects in hydrolysis and absorptive surfaces in the gut45. It is particularly common in inflammatory diseases such as coeliac disease46, IBD47 and pancreatitis48.

Supporting Digestion & AbsorptionDigestive�enzymes, HCl and pepsin are an ideal first line treatment for many conditions where poor digestion is implicated. Research suggests that enzyme therapy can relieve symptoms associated with pancreatitis49 and specific enzymes such as lactase, lipase and gluten protease can improve the digestion of lactose50, fats51 and gluten52. However considering the use of enzyme therapy in these cases can be tricky, particularly if areas of the gut mucosa are inflamed and unprotected against the protein-degrading effects of proteases.

When considering supplementation, it is important that nutrients are in a form that is easily absorbed and assimilated by the body, particularly if digestive function is impaired. The best example of this is the use of chelated minerals or utilising organic acids alongside minerals to improve absorption, for instance calcium citrate is better absorbed than calcium carbonate53. Technology can also aid absorption, the use of emulsified fat-soluble nutrients (e.g. vitamin A and vitamin E) and essential fatty acids can significantly improve bioavailability54,55,56.

The Lower GI TractThe lower gastrointestinal tract includes most of the small intestine (lower duodenum, jejunum and ileum), the colon and the anal canal. The colon is critical for ridding the body of waste and the absorption of water, sodium and other nutrients that have escaped absorption in the ileum. It is also an immune barrier and home to the largest numbers of microorganisms in the body. Later on, we will discuss the significance of the microflora in health and disease.


MotilityMotility refers to the ability to move food through the digestive tract. It is reliant upon on a number of factors, including peristalsis, digestion, integrity of intestinal cells, the consumption of soluble fibre and the gut microflora. Peristalsis is a distinctive pattern of smooth muscle contractions that propels foodstuffs through the oesophagus and intestines. It is mediated by the intestine’s local, intrinsic nervous system. Excitation is controlled by acetylcholine and substance P, whilst inhibition is controlled by nitric oxide, vasoactive intestinal peptide and ATP. The speed of movement of foodstuffs is important to proper digestion, absorption and excretion. Disorders of motility may contribute to IBS, constipation, diarrhoea and food allergies.

The Gut-Brain ConnectionOne of the most important factors controlling motility is the connection between the brain and the enteric nervous system, which is a system of neurons that governs the functions of the GI system. The brain communicates with the enteric nervous system through multiple parallel pathways. The vagal pathway interfaces with the parasympathetic nervous system, which is associated with rest and relaxation. This nicely demonstrates the importance of relaxation for digestion but also highlights the connection between mood and GI disorders57. The vagus nerve stimulates digestive secretions, peristalsis and blood flow in the GI tract. The splanchnic nerves carry mostly sympathetic fibres which detect changes in neurotransmitters and other stimuli in the gut and relay these messages back to the brain58.

Serotonin & Melatonin – a delicate balanceThe enteric nervous system makes use of many neurotransmitters, such as acetylcholine, dopamine, serotonin and melatonin59, which are located in the enterochromaffin cells in the gut60. Changes in levels of serotonin can alter sensitivity to serotonin signalling, change motility of the bowels, influence intestinal fluid and mucus secretion, and intestinal sensitivity to sensations like pain and fullness. Long-term use or the wrong dosage of selective serotonin re-uptake inhibitors (SSRIs) may cause fluctuations between nausea, vomiting, constipation and diarrhoea, as well as depression, anxiety, insomnia, and changes in appetite.

Melatonin is also produced by the enterochromaffin cells in the gut, which produce 400 times more melatonin than is found in the pineal gland61. Enteric melatonin is capable of acting as a protective antioxidant as well as a neurotransmitter carrying information between gut and brain, regulating gastric emptying and peristalsis. Trials using melatonin and methylation factors on patients with gastrointestinal reflux disease showed 100% relief after 40 days compared with 66% relief with proton pump inhibitors (PPIs) 62.

Evidence is accumulating that gut microbes may be involved in neural development and function, both peripherally in the enteric nervous system and centrally in the brain.

The Microflora-Brain AxisA stable gut flora is essential for normal gut physiology and contributes to appropriate signalling along the gut-brain axis.Dysbiosis can adversely influence gut physiology, leading to inappropriate gut-brain axis signalling and associated consequences for central nervous system functions, thus resulting in disease states. Our microflora produce neuro-active molecules such as serotonin, melatonin, GABA, catecholamines, histamine and acetylcholine63. These chemicals influence reward and satiety pathways, production of toxins that alter mood, changes to receptors, including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain64. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related gut-brain axis disorders.65

ConstipationConstipation refers to bowel movements that are infrequent or hard to pass. Other symptoms include fatigue, lethargy, abdominal pain, skin conditions, headaches and haemorrhoids. There are multiple related conditions such as diabetes, depression, hypothyroidism and chronic renal failure. In addition, various frequently used drugs (including antidepressants) cause disordered gastrointestinal motility66. Key underlying factors include a lack of dietary fibre, poor hydration, imbalanced microflora, poor gut motility and stress.

Support for ConstipationNutritional treatments include pre and probiotics, botanicals and soluble fibre. These approaches should potentially help as they soften and bulk the stool, cleanse the colon and provide a gentle laxative effect. FOS increases probiotic bacteria67. Burdock possesses antimicrobial activity against both gram-positive and gram-negative bacteria68. Psyllium husk69 and prunes70 act as natural, gentle laxatives. FOS71 and rhubarb also act as natural laxatives. Oral administration of Bifidobacterium infantis has been shown to increase tryptophan levels as well as alter serotonin and dopamine turnover in the frontal cortex and limbic system72, which could have significant effects upon serotonin release in gut enterocytes and subsequently influence motility.

A Summary of the Latest and Most Useful Probiotic ResearchGut Health in Practice


EfferentSecretionMotility

Blood Flow

Vagal Pathway

Splanchnic Pathway

AfferentNeurotransmitters

NeuropeptidesOther Chemical &Mechanical Stimuli

CNSCortex, limbic system, brain stem

Enteric Nervous System

Clinical Focus: Irritable Bowel Syndrome (IBS)Irritable Bowel Syndrome (IBS) is understood to be a multi-factorial condition73, which manifests as a muscular and functional disturbance of the bowel. The condition affects 10-25% of the UK population. About half of people with IBS consult their GP and 20% of these are referred to a consultant74. Women are more likely to develop IBS than men. Symptoms of IBS include: abdominal pain or discomfort, altered bowel habits (constipation or diarrhoea or alternating), mucus discharge and sensations of bloating, urgency or incomplete evacuation.

The pathogenesis of IBS still remains uncertain75, but the following factors may lead to the development and maintenance of symptoms:

Psychological� /� Neurotransmitter� /� Endocrine� Function�dysfunction at the gut-brain axis, with alterations in the components of central and peripheral nervous system and social stress contribute to this disorder. Recent evidence supports the theory that modulation of serotonergic mechanisms significantly impacts the manifestations of IBS76. Stress and anxiety contribute to autonomic imbalance. IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain77.

Immune� Function� -� both colonic and small bowel inflammation have been discovered in a subset of patients with IBS78. Increased interleukin-1β mRNA expression in both the recto-sigmoid region and ileum was demonstrated as well as other inflammatory markers including IL-1, IL-6, TNF-α, and a depressed IL-10/IL-12 ratio79.

Visceral�Hypersensitivity�-�thought to be related to modulation of visceral sensory neurones, involving a complex interaction of cytokines, neuronal transmitters and nerve factors80. Enteroendocrine cells in post-infectious IBS appear to secrete high levels of serotonin, increasing colonic secretion and possibly leading to diarrhoea.

Motility�- smooth muscle hyper-responsiveness can result in delayed meal transit in patients prone to constipation and in accelerated meal transit in patients prone to diarrhoea.

Microbiota� - Campylobacter, E- coli 0157 and Salmonella have been linked to bloating and distention81. Parasites such as Blastocystis hominis and Dientamoeba fragilis82 and raised IgG antibody levels to B.hominis83 have been implicated.

Intestinal� permeability, food� sensitivities and lactose�intolerance may also contribute to symptoms and underlying imbalances.

Supporting IBSDue to the complex and highly individual nature of IBS it is important to investigate underlying barriers to recovery such as food sensitivities, stress and trigger foods (coffee, fizzy drinks, alcohol, etc.). Adopting a gluten-free diet could be useful for reducing symptoms associated with IBS84. Mindfulness-based therapies could provide some benefit in IBS and other functional GI disorders85. A low FODMAP diet can provide initial symptomatic relief 86, but should not be relied upon long term as it eliminates many healthy foods and doesn’t effectively tackle any potential underlying dysbiosis.

The next stage involves soothing inflamed tissue and reducing spasms:

•�Chamomile is an anti-spasmodic, mild sedative (serotonergic)87 and anti-inflammatory88.

•�Peppermint� is a smooth muscle relaxant that may reduce cramping and pain with IBS89.

•�Fennel�inhibits spasms in smooth muscles90 and cardamom has been shown to exert anti-spasmodic properties in animals91. Ginger aids digestion92 and improves motility93.

Always consider dysbiosis and treatments which can beneficially modulate the microflora:

•�Probiotics: LAB4 probiotics reduced severity and duration of abdominal pain, bloating, improved bowel movements and quality of life scores in just 8 weeks94.

• Probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitisation and/or activation95.

•�FOS� (fructooligosaccharides)� increase faecal output96, moisture97, mass, short chain fatty acid content and decrease constipation98.


Stress

Enteric Nervous System

Neurotransmitters & Peptides

Endocrine

Immune Function

Motility

Microbiota

Visceral Hypersensitivity

Gut Microbiota

Total IBS Symptom Level

Tota

l lev

el IB

S Sy

mpt

oms

0 2 4 6 8 10

LAB4 Ends

Weeks

Informed Sport RangeIntegrity & ImmunityA helpful analogy for the gut immune system is an army in the midst of war. The gut wall needs to be structurally sound in order to prevent infiltration by pathogens, in the same way that the wall surrounding an army base needs to be structurally sound in order to prevent infiltration by the enemy. Furthermore the immune cells in and around the gut wall need to be functioning correctly to destroy incoming pathogens, in the same way that soldiers need to be healthy and well equipped in order to protect against invaders. In other words, the integrity of the gastrointestinal tract is one of the key barriers that interfaces with our external environment and is essential for ensuring an appropriate immune response. The breach of the intestinal barrier by pathogens and other substances causes an immune response which affects not only the gut, but also other organs and tissues. These include the skeletal system, the pancreas, the kidney, the liver and the brain.

Maintaining Intestinal StructureThe gut mucosa consists of epithelial cells, the lamina propria (layer of connective tissue) and the muscularis mucosae (thin layer of smooth muscle that aids peristalsis). One of the most important functions of epithelial cells is to form a barrier of tight junctions. Zonulin is a protein that acts as a gatekeeper of these tight junctions. Disruption of zonulin and damage to epithelial tissue leads to intestinal hyperpermeability (so-called “leaky gut”)99. Allergies, systemic inflammatory response syndrome (SIRS), IBD, autism, IBS, coeliac disease, ankylosing spondylitis, rheumatoid arthritis, dermatitis, obesity and insulin resistance have all been associated with intestinal permeability100. When permeability increases, barrier defences decrease, meaning viruses, bacteria and/or endotoxins and other antigens are able to enter systemic circulation. The immune system swiftly reacts by recruiting inflammatory cytokines, which leads to intestinal and systemic inflammation, malabsorption, food sensitivities and autoimmunity. This creates a self-perpetuating cycle as increased levels of inflammation lead to sustained intestinal permeability101.

So why and how does intestinal permeability occur? The gut barrier is continuously challenged by lectins102, gliadin103, glycated foods, endogenous and exogenous irritants, excess secretion of acid and pepsin, reactive oxygen species, ethanol, NSAIDs, excessive stress, H pylori & other pathogens. These challenges can lead to disrupted zonulin and subsequently leaky gut. Transitional permeability is normal in some circumstances, such as in babies and in adults following consumption of alcohol, spices, and NSAIDs, but it should revert quite quickly.

The lamina propria provides a structural foundation for the intestinal epithelium. It is a layer of loose connective tissue consisting of a meshwork of reticular fibres, collagen, elastic fibres and lymphoid tissue, and also lymphocytes including IgA-secreting B cells. Without a solid extracellular matrix, the function of these immune and epithelial cells can be impaired and intestinal hyperpermeability is increased. The sub-mucosa provides denser connective tissue support. Recent observations suggest that cytokines derived from lymphoid cells are also important regulatory factors for the growth and differentiation of gut mucosal tissue104.

The Gut-Immune ConnectionSome level of assault on the intestine occurs at all times, thus it is the natural state of the intestine to be immunologically and chemically challenged. The gut immune system contains 70–80% of the body’s immune cells105, which are densely packed into gut-associated lymphoid tissue (GALT). GALT consists of a mixture of lymphoid tissues which harbour immune cells such as T and B lymphocytes that are able to attack pathogens. Fortunately GALT is distributed throughout the GI tract: tonsils, adenoids, Peyer’s patches (small intestine) and lymphoid aggregates in the oesophagus and large intestine. Plasma cells in the connective tissue lining of the gut (lamina propria) secrete IgA antibodies into mucous to neutralise the threat of pathogens and inhibit inflammatory effects of other immunoglobulins. The gut flora modulate gut immunity in a number of ways.

The hygiene hypothesis states that a lack of early exposure to microorganisms can lead to immune dysregulation and could even partly explain the recent rise in chronic inflammatory disorders such as allergies, autoimmunity and inflammatory bowel diseases106,107. Absence of the microbiota in germ-free mice causes developmental defects in the immune system. These mice have: fewer plasma cells and intraepithelial lymphocytes, lower IgA levels and smaller Peyer’s patches108. The microflora induce the release of immune cells - cytokines IL-10, IL-12 & IFN gamma and sIgA109. The presence of pathogens such as giardia is linked to reduced tolerance of antigens and low levels of sIgA110. If the immune system in the gut isn’t functioning correctly it can lead to dysbiosis, frequent infections and systemic immune problems.



Defective Intestinal Barrier

Intestinal inflammation

Increase in intestinal permeability

Exposure to environmental endogenous permeability

stressing factors

Activation of immune response

Systemic autoimmunity

Increase in intestinal penetration of luminal

antigens

AutoimmunityAutoimmune diseases are characterised by tissue damage and loss of function due to an immune response that is directed against specific organs111. We are now seeing an increase in both the incidence and prevalence of up to 80 different auto-immune conditions112. In the past, coeliac disease and other autoimmune diseases have been linked to genetic predisposition, however it is clear that environmental factors have a large role to play. It is also important to note that once the autoimmune process is activated, it is not self-perpetuating - it can be modulated or even reversed by preventing the continuous interplay between genes and environment113.

- Recent data suggest there is mucosal inflammation in the small intestines of patients with type 1 diabetes and Hashimoto’s thyroiditis - suggesting altered gut permeability and/or immune dysregulation114. Zonulin dysfunction and subsequent leaky gut is now regarded as a precondition to developing autoimmunity115.

- Autoimmunity is often characterised by Th1 immune dominance. The gut microflora is critical in modulating immune development from a young age. Certain species of bacteria are able to modulate the balance of Th1/Th2 immunity.

- Vitamin D deficiency has consistently been found across a number of autoimmune diseases. Furthermore, countries further away from the equator with less potential exposure to stronger UV radiation, tend to have higher rates of autoimmune conditions such as multiple sclerosis.

- Certain sequences of amino acids have the ability to trigger reactions. In coeliac disease it is possible that you are not only sensitive to gluten but probably many other non-gluten containing foods that have similar amino acid sequencing, for example cow’s milk and grains containing gluten116. This is known as cross-reactivity or “molecular mimicry”.

Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens.

Supporting Gut Integrity & ImmunityGut enterocytes have an amazing capacity to heal, but only if they are free from constant attack and have access to the right nutrients. A back-to-basics approach really is important for intestinal integrity. Something as simple as losing weight and balancing blood sugar could help, given the recent evidence which associates obesity and insulin resistance with higher circulating levels of zonulin and intestinal permeability117. If autoimmunity is indicated then a gluten and dairy free diet could help to reduce circulating levels of zonulin. Food sensitivity testing with avoidance or rotation of problem foods should be considered in any case of intestinal permeability.

The next most important step is to provide therapeutic levels of nutrients associated with improved barrier function and connective tissue growth:

•�L-glutamine improves intestinal barrier function118 and intestinal permeability119.

•�N.A.G. promotes growth of mucosal tissue120 and binds to lectins, helping to neutralise them. N.A.G. inhibits secretion of interferon-γ, tumour necrosis factor-α, IL-17, and IL-22121.

•�Gamma�oryzanol is a plant sterol from rice bran oil that normalises vagus nerve stimulation of gastrin122, has potent antioxidant activity123 and an anti-ulcerative action on gastric lesions124.

•�Vitamin�E is a potent antioxidant which protects epithelial tissue125.

•Zinc helps to tighten epithelial junctions in Crohn’s disease126.

•�Probiotics modulate the integrity of the junctions between intestinal mucosal cells in healthy adults127.

Reduce inflammation and support immunity:

•�Vitamin� D plays a critical role in the integrity of tight junctions and the healing capacity of the epithelium128. It regulates immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells129.

• There is a significant reduction in inflammatory markers such as TNF-α and IL-6 following probiotic supplementation130. Lactobacillus salivarius has been shown to increase IgA131 and the regulatory IL-10, and reduce mucosal levels of inflammatory cytokines132. It has been shown to downregulate proinflammatory cytokines in gut tissue samples taken from Crohn’s sufferers133.

•�Bioflavonoids like quercetin block histamine and inhibit mast cell degranulation134.

•�Glutamine� and curcumin� both inhibit inflammation and oxidative stress linked to tight junction opening135.

•�Fish�oil reduces inflammation through the action of EPA in promoting anti-inflammatory prostaglandins136.

•�Whey�protein contains natural levels of immunoglobulins that help to promote sIgA function and promotes glutathione synthesis, which plays an antioxidant role and enhances gut healing.

If impaired digestive function is implicated, digestive enzymes help break down food proteins and reduce reactivity.


MicrofloraThe human gut is host to a highly complex ecosystem of microorganisms, the functions and interactions of which are largely still unknown. The gut flora alone comprises an astonishing 95% of the total number of cells in the human body – 100,000 billion organisms. There is developing evidence that an imbalance in these bacteria has significant implications for health.

DysbiosisWe need to consider not just how fungal overgrowth may challenge the digestive system, but in fact the whole range of digestive imbalance (‘dysbiosis’) and beyond (liver function, homeostasis). Dysbiosis refers to a microbial imbalance, on or inside the body. We’re now going to take a look at the main causes of dysbiosis and best courses of action when faced with an imbalanced microflora.

Causes of DysbiosisColonisation of pathogenic bacteria and compromised levels of beneficial and commensal bacteria can lead to state of dysbiosis in the gut137. Factors that may lead to dysbiosis are:

•�Antibiotics. Use of antibiotics can alter the composition of the human intestinal microflora138,139 and may also impact upon individual susceptibility to Salmonella infection140.

• Hypochlorhydria (low stomach acid). A commonly held belief is that the stomach acid serves as a barrier to pathogenic microorganisms. A study by Tennant et al (2008)141 found that hypochlorhydric mice had significantly greater numbers of Yersinia, Salmonella, and Citrobacter cells and Clostridium spores following infection than mice with normal gastric secretion.

•Exposure�to�pathogens in foods, water, animals, other people.

• Trauma�and�stress. High levels of cortisol relate to low levels of sIgA142, lowering the mucosal output in the protective layer of mucus on the gut wall. High cortisol and low DHEA slow the turnover of mucus143.

•Surgery.

•�Compromised� immune� system/gut� microflora. Microflora induced resistance to infection has been demonstrated against many bacterial & fungal pathogens144,145. The presence of Lactobacilli in the small intestine was the major factor that increased resistance to Giardia infection146.

•�Lack�of�fibre. Fibre physically cleans the gut and encourages the removal of static food which otherwise encourages growth of undesirable bacteria and pathogens. Fibre also provides carbohydrate for beneficial bacteria to ferment.

The Dysbiosis CascadeMaintaining homeostasis is vital for health and the individual is constantly challenged by its internal and external environment to balance capacity and demand. For a time the organism will achieve this, but at a cost. If demand outstrips capacity regularly there will be a trade-off in terms of system dysfunction. When the gut is compromised there is both increased demand and reduced capacity to deal with its consequences at the most fundamental level. There is a resulting cascade effect throughout the organism in the following specific areas:

• Healthy microbial�balance is essential for proper digestion and absorption of nutrients. The gut microbiota acts as a “metabolic organ”, breaking down food groups and generating fermentation end-products (e.g. short chain fatty acids) and also producing vitamins, assisting ion absorption and conversion of dietary polyphenolic compounds into their active form147,148.

• There is a consequential effect on liver�function and detoxification mechanisms. Presence of inappropriate bacteria in the upper gut causes fermentation to occur in the wrong place. The metabolic by-products then have to be detoxified by the liver cytochrome P450 detox system. Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability may also be involved in the pathogenesis of liver disease. Probiotics have been suggested as a useful integrative treatment of different types of chronic liver damage, for their ability to augment intestinal barrier function and prevent bacterial translocation149.

•�Insufficiently�digested�foods impair the homeostatic balance of the digestive tract and may pass through an excessively leaky gut mucosa, triggering food allergy reactions or mimicking enzymes and hormones. For example, a strip of amino acids Ser-Tyr-Set-Met could mimic adrenocorticotropic hormone (ACTH) - the hormone which stimulates the adrenal gland. An 8 amino acid fragment might act like glycogen and so deplete glycogen stores in the liver150.

• The upset�mucosal�barrier plus the wider immunological effect results in a heightened state of inflammatory response and reduced barrier function. Stimulation of the immune system on the gut wall by probiotic bacteria induces downregulation of inflammatory markers such as NF-κB151, TNF-α, IL-8, and IL-1β152. Compromised secretory IgA may inhibit its ability to regulate microbial intestinal colonisation and pathogen attachment153.

As you’d expect, dysbiosis has been directly linked with a number of gut disorders, such as Inflammatory Bowel Disease (IBD). In IBD decreased numbers of protective Lactobacilli and Bifidobacteria have been observed154, while intestinal parasites such as Blastocystis hominis, Endolimax and Entamoeba histolytica have been shown to be common in cases155. Similarly, low secretory IgA is important as a defence mechanism in the gut mucosa and correlates with the incidence of ulcerative colitis156.

However, naturopathic and environmental medicine practitioners would take this further and postulate that dysbiosis can be central to other types of disease via the mechanisms described above. For example, seemingly unrelated symptoms such as headache, arm pain, shoulder pain, myalgia, palpitations and sleep disturbance may be linked to enterococcus infection, and post-exertional fatigue, photophobia, mind going blank, palpitations, dizziness, faintness are linked to streptococcus157.




Candida albicansCandida albicans is a normal resident of the intestines and is generally kept in check by a vigorous probiotic microflora and an active immune system. A large presence in stools may not give a good indication of how much of a problem it is creating, and a better option may be a salivary test to screen for antibodies. Candida also needs to take root in the intestinal wall in its mycelial form to really cause any mischief. As the yeast proliferates the branching hyphae penetrate the gut wall causing leaky gut syndrome. The toxic candida by-products of ethanol and acetaldehyde from metabolism can then be found in the blood and, as the permeability of the intestinal lining increases, the candida can seep into the blood to cause infections and allergenic reactions in other parts of the body.

If Candida is viewed to be a major factor in a given client’s situation, then it must be treated with care and taking into consideration the true underlying causes. Using antifungals alone will only provide a temporary solution. Be very wary of restrictive diets. To completely starve Candida you would have to eliminate practically all carbohydrate from the diet, something that is neither possible nor desirable as many beneficial, nutritious foods contain natural starches. Sugar should be controlled in the diet, but we now believe that it is sugar in circulation that is of the most importance because it encourages Candida to migrate to the gut wall. Therefore prescribing a diet that helps to balance the levels of blood sugar is more important than slavishly cutting all carbohydrate and sugar. This will also address any issues with energy and homeostasis, enabling the body to restore health.

ParasitesParasitic infestation is another major cause of dysbiosis. Symptoms are very similar to those associated with Candida albicans. Risk factors for acquiring such unwelcome guests include foreign travel, exposure to small children or pets, spending time outdoors, poor immune status, use of untreated water, and consumption of some uncooked foods like salad greens.

Parasites most commonly identified via testing include Blastocystis hominis, Dientameoba fragilis and giardia.

Treating DysbiosisSuccessful treatment is based on looking past the specific issue and treating the client holistically. Addressing blood sugar regulation, supporting detoxification, and improving the digestive capability using enzymes and probiotics are all vitally important. Natural anti-inflammatories such as curcumin158, fish oils159 and flavonoids160 should also be utilised. Stool testing can be indicated if initial treatment doesn’t help.

The second stage of dysbiosis treatment involves the use of higher potency probiotics alongside active targeting of specific pathogens with the use of antimicrobial plant oils. It would appear that using multiple oils may be more effective than single antimicrobials, and that there is also less likely to be resistance developed by the pathogens because of their multifactorial effects161 162. A further clinical consideration is whether oils need to be effective systemically or targeted to the gut area. Food oils, especially if emulsified, will be progressively absorbed in the digestive tract. This is helpful for systemic infection, but may mean that the oil is not active over the whole course of the intestines. Alternatively, time-release products will retain their activity up to and including the large intestine, and are better suited where a targeted effect is needed.

At this point, if antimicrobial treatment has proved ineffective it could be that more hardy colonies of pathogens in the form of biofilms have taken root. Biofilms are an aggregate of microorganisms encased within a self-produced matrix of extracellular polymeric substances163. Biofilms act as a unique cloaking device effectively protecting the microorganism from immune surveillance and they also increase antibiotic resistance164. Antimicrobial agents such as proteolytic enzymes can be used to target biofilms165 and evidence suggests that N-acetyl cysteine (NAC) can also disrupt biofilm formation166.

The third stage of dysbiosis treatment involves the repair and maintenance of the intestines. The use of integrity support as discussed earlier will help to heal damage caused by dysbiosis. It may also be useful to continue use of lower potency probiotics and broad spectrum antimicrobials such as garlic. The next page provides a summary of some of the most useful natural antimicrobials and their specific uses.

Stage 1Preparation

diet Digestion General wellness

Digestive enzymes

Energy/VitalityProbiotics

Antifungal combinationProbiotics

Liver supportEnzymes

GarlicProbiotics

Permeability support

Stage 2Dysbiosis treatment

Stage 3Maintenance

Biofilms? Something else?



Nature’s Antibiotics

Antimicrobial Info/Mechanisms Organism

Oregano Oil

Thymol and carvacrol contents are responsible for its antimicrobial and antifungal effects167. The cause of the antimicrobial properties is believed to be disruption of the bacteria/fungal membrane168 169. Oregano oil is absorbed through the lining of the digestive tract making it systemically effective throughout the�body170.

Oregano presents antimicrobial activity against pathogenic microorganisms like Salmonella typhimurium, Staphylococcus aureus, Staphylococcus epidermidis and Candida Albicans171. In some pathogens, such as Pseudomonas aeruginosa it causes damage to the cell membrane of these bacteria. Carvacrol has been shown to inhibit the growth of several bacteria strains, e.g. Escherichia coli and Bacillus cereus172.�Case studies show emulsified oregano oil to be effective against�Entamoeba hartmanni , Endolimax nana, and Blastocystis hominis 173,174, and further evidence shows efficacy against resistant strains such as Stenotrophomonas maltophilia MU 64, S. maltophilia MU 99, and Chryseomonas luteola MU 65175.

Clove Oil

Contains high concentrations of eugenol, which shows a broad spectrum of activity against a variety of pathogenic yeasts and filamentous fungi176. Helps to inhibit germ tube formation, whereby Candida Albicans may spread systemically177. It successfully inhibits the growth of mycotoxigens, regulates production of fumonisins and prevents formation of aflatoxins178.

Clove oil is effective against yeast and fungi such as Candida Albicans,

C. tropicalis and C. parapsilosis, including strains with decreased susceptibility to fluconazole such as C. krusei and C. glabrata179. It has also shown inhibitory activity to Listeria monocytogenes, Campylobacter jejuni, Salmonella enteritidis, Bacillus cereus, E coli, Staphylococcus aureus180, Aspergillus parasiticus and Fusarium moniliforme181.

Cinnamon Oil (Cinnamomum zeylanicum)

Various terpenoids such as eugenol and cinnamaldehyde found in the volatile oil are believed to account for cinnamon’s effects. Both cinnamaldehyde and cinnamon oil vapours have been shown to be potent antifungal and antibacterial compounds182 183.

The fungitoxic properties of the oil or its active constituent have been established against Aspergillus niger, A. fumigatus, A. nidulans A. flavus, Candida albicans, C. tropicalis, C. pseudotropicalis, and Histoplasma capsulatum. In studies, potent antimicrobial activity has also been shown against Bacillus subtilis, Bacillus cereus, Campylobacter jejuni, Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Haemophilus influenzae, Salmonella choleraesuis, S. enterica, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and S. pyogenes, as well as Yersinia enterocolitica184 185.

Garlic

Garlic has broad-spectrum antimicrobial effects. It contains allicin and ajoene, which exhibit multiple inhibitory effects on various thiol-dependent enzymatic systems within bacteria. Dehydrogenases or thioredoxin reductases may also be affected at high concentrations186. Garlic is selective in its inhibition, so does not exert a negative effect on beneficial probiotic bacteria.

Garlic is effective against Gram-negative and Gram-positive bacteria including species of Escherichia, Salmonella, Staphylococcus, Streptococcus, Klebsiella, Proteus, Bacillus, and Clostridium187. Garlic extracts are effective against H. pylori188. Allicin also inhibits protozoan parasites such as Giardia lamblia, Leishmania major, Leptomonas colosoma, and Crithidia fasciculate. Garlic has a strong antifungal effect against species such as Candida Albicans, Cryptococcus, Trichophyton, Epidermophyton, and Microsporum189, and prevents the formation of mycotoxins like the aflatoxin of Aspergillus parasiticus190.

Caprylic Acid

Caprylic acid has antibacterial, antiviral and immune system-stimulating effects. Due to its relatively short chain length, caprylic acid has no difficulty in penetrating fatty cell wall membranes, hence its effectiveness in combating certain lipid-coated bacteria191 192. Caprylic acid also works by disrupting the replication of yeast cells. It has mild anti-inflammatory properties and may help to soothe some of the irritation on the gut wall caused by candida overgrowth.

Caprylic acid has a fungicidal effect on multiple species of Candida, of which Candida Albicans strains are particularly sensitive193. Caprylic acid suppresses mycelial growth in a range of fungi, including Fusarium oxysporum194. Caprylic acid also exhibits antimicrobial properties, inhibiting Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Staphylococcus aureus, and Escherichia coli195. It has been found to inhibit Listeria monocytogenes when combined with oregano oil196.

Probiotics

Probiotics ameliorate dysbiosis by occupying the intestinal space and actively secreting bacteriocins, which act like natural antibiotics within the gastrointestinal system197. Where antibacterial herbs are contraindicated they are a great alternative. Even if antibacterial compounds are used, the long term success of any programme depends on maintaining balanced microflora and probiotics have a key part to play.

Lactobacillus species (e.g. L. acidophilus, L. salivarius) help to modify the pH of the intestinal environment through production of lactic acid, rendering it less hospitable to opportunistic microorganisms198, such as bacteria, fungi and parasites, including Salmonella, Shigella and E. coli 199. Lactobacillus salivarius produces bacteriocins such as ABP-118 that kill Listeria monocytogenes and inhibit growth of H. pylori 200. Both Lactobacilli and Bifidobacterium also kill Klebsiella pneumonia, Yersinia pseudotuberculosis and Staphylococcus aureus201. At least two trials have shown that supplementation with probiotics following antibiotic use prevent multiplication of Candida Albicans202 203.


Prebiotics - Friend or Foe?Prebiotics selectively stimulate the growth and/or activity of a limited number of bacteria in the colon. However prebiotics like FOS (also known as inulin) seem to be getting a bad press. It’s incorrectly thought that FOS feeds bad bacteria as well as good, and side effects to probiotic supplementation are attributed to FOS. However scientific studies to date show two things: firstly that FOS preferentially encourages growth of beneficial bacteria and secondly that clinical data is proving FOS’s efficacy across the board. On the rare occasions that clients react to ‘synbiotic’ products - those containing both pre and probiotics - it is usually because the positive change to the microbiota is happening too quickly and the treatment programme needs to be modified. This is because supplementing FOS with probiotics multiplies its effectiveness. Whilst it is theoretically possible for FOS to feed some less favourable bacteria, in reality its effect is to substantially affect probiotic bacteria in a beneficial way. The table opposite summarises the evidence on how FOS positively affects the balance of flora in the gut. The Moro study in particular explodes the myth that FOS feeds Candida albicans, and in fact promotes colonies of probiotic bacteria quite significantly.

AmountFOS Fed

SignificantIncrease

Significant Decrease No Change

15g/day, 15 days

BifidobacteriaBacteroidesFusobacteriaClostridia

LactobacilliGram positive cocciColiforms204

8g/day, 35 days

Bifidobacteria Bacteroides205

10g/litre, 28 days

Bifidobacteria

BacteroidesClostridiaE. coliKlebsiellaCitrobacter Candida albicans206

18g/day, 12 days

Bifidobacteria/Lactobacillus207

5-20g, 8 days

Bifidobacteria208

Conclusions

Understanding and addressing GI health is critical to supporting the health of clients. It’s important that treatment is implemented in

the context of their overall needs to be effective. General digestion, blood sugar, detoxification, and intestinal integrity are all central.

To improve the health of the gut it is important to consider all aspects. Start by ensuring digestion, absorption and motility are optimal.

Digestive enzymes and calming herbal extracts such as slippery elm can help. Removing inflammatory foods and including healing

nutrients can support gut integrity and systemic immunity. Ensure that any underlying dysbiosis is tackled, potentially by using broad

spectrum antimicrobials in combination with probiotics. There is no exclusive order in which to tackle gut issues, but by taking a

systematic approach it is likely that you can bring long term positive effects to the health of the gut and therefore the patient.



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76490 Eradicidin Forte® £14.35 £25.70 Time-released garlic, oregano, cinnamon and cloveHigh strength bacterial balance support

52060 Oregano Complex £13.74 £24.60 Micellised oregano with freeze-dried garlic, borage, grapeseed, clove and ginger grass

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Key Gut Health ProductsCode Product Trade Price

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References


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