This section of your report list genetic markers and your SNPs associated with Gut level inflammation. 

Start with addressing this aspect of your wellbeing if your long term goal is to descrease inflammation, improve immune system function, detoxification, mitochondrial function, methylation and neurotransmitter balance.

One caveat to consider here may be raised levels of Homocysteine: homocysteine is pro-inflammatory and may impact your gut permeability.

High homocysteine may indicate the need for some level of methylation pathway support already at this stage. Talk to your Practitioner about strategies geared towards lowering your Homocysteine levels, if they are indeed high, during addressing of your Gastro-Intestinal health bearing in mind that aggressive and direct targetting of the folate pathway is not advisible in conditions characterised by high oxidative stress and inflammation. We wrote about this in our Report Introduction article. 

Please note that many substances commonly used to address inflammation and gut health may also impact the levels of your neurotransmitters.

Your specific genotypes, listed under the NEUROTRANSMITTERS section, may influence how you react to these substances, as far as mood and cognitive processing are concern

SYSTEMIC EFFECT OF GUT INFLAMMATION

Modern science has validated what ancient healing traditions have known for centuries: the GI tract has a central role in chronic, systemic disease.

Intestinal microbiota produce vitamins, neurotransmitters and other molecules that can impact every cell and organ in our body.  If your gut isn’t in an optimal condition, then the healing process is slowed and you may struggle longer than necessary.

There is a very good reason why we have included the GI Health section in our Genetic Variant Report, and also why you see it at the the top of our original Functional Healing Planner.

From intestinal pathogens and allergens, to intestinal permeability and imbalances in colonic microbiota, the subcategories listed in your report were created to highlight genetic susceptibilities towards gut dysfunctions which are able to seriously compromise overall health:

• Immune modulation and Inflammation: including conditions like IBS, IBD, Crohn’s diesease (ATG16L and HTR2A genes) and Celiac and gluten sensitivity (HLA-DQA1 gene). We have also focused on highlighting predispositions to overproduction of pro-inflammatory cytokines like TNF and IL-6 or under-production of anti- inflammatory cytokines like IL-10.
• Gut microbiota diversity and dysbiosis: especially Bifidobacterium  population (via H Antigen secretion – FUT2 gene) and Clostridum Difficile overgrowth (ACAT1 gene).
• Microbial defence through pathogen recognition and immune signalling: (genes MPO and PON1).
• Gut permeability: with a focus on the PEMT gene, connected to cell membrane permeability, and the genes connected to histamine intolerance (DAO/AOC1). Gluten sensitivity will also play a very important role here.

The intimate relationship between your gut and mechanisms whose dysfucntion can result in systemic diseases, makes it the fundamental area of focus in efforts to re establish proper functioning of your body’s core systems:

• The Detoxification system: your gut has higher metabolic activity than your liver. Inflammation in your intestinal tract can slow down carrier proteins whose job is to remove toxic conjugates produced in the liver and tranposrted through the bile ducts and the gut.
• Methylation and downstream epigenetic modifications: this organ houses a genome which is 100 times larger than just the human genome. Several strains of gut commensal bacteria have now been identified as producers of B vitamins – including folate.
• Mitochondrial function: various mechanisms resulting from inflammatory processes, originating in the gut, can suppress energy production in the mitochondria through oxidative stress build up and detox pathways inhibition.
• Cognitive and mental health: through its relationship with the Central Nervous System: your gut produces 75% of your neurotransmitters or their precursors. The levels of your Neurotransmitters can also be impacted directly by high oxidative stress and inflammatory cytokine levels – your gut can be a significant source of both.
• Immune system balance: your gut contains two thirds of your immune tissue.
• Molecular mimicry: Antigens may possess similar antigenic determinants as human tissue. Translocation of microbial components may result in antibody production and cross reactivity. This may lead to your immune system getting confused and starting to target parts of your own tissues. 
• Hormonal balance: there is a very close relationship between your immune, central nervous and endocrine system sygnalling. If one is thrown out of balance, the other two could follow suit.
• Nutrients absorption and delivery: your intestines contain 10 times more cells than the rest of your body.

In this overview we will be focusing on listing the types of problems, as well as signs and symptoms, indicative of gastrointestinal dysfunction. In the subsequent articles we will be connecting the dots between these undesirable processes and their systemic effect.

Most common gastrointestinal problems and how to identify them: 

1. Hypochlorhydia

Gastric inflammation (Gastrisis) is strongly associated with hypochlorhydria because many of the causes of hypochlorhydria actually cause atrophy of the gastric lining. An untreated gastric inflammation can lead to frank gastritis, which is strongly associated with burning of the stomach and potentially even vomiting blood.

Adequate HCl in your stomach is needed for:

• Secretion of the intrinsic factor and thus vitamin b12 absorption.
• Absorption of vitamins and minerals.
• Protein absorption and metabolism.
• Bile Production.
• Antimicrobial activity.

Causes:

• Helicobacter pylori infection is strongly associated with hypochlorhydria. If a patient has persistent hypochlorhydria, presents with ulcer symptoms, or complains of chronic stomach burning, H.pylori infection should be ruled out.

Signs and symptoms of Hypochlorydia:

• Bloating, belching, burning, and flatulence immediately after meals.
• A sense of fullness after eating.
• Indigestion, diarrhoea, or constipation.
• Multiple food allergies.
• Nausea after taking supplements.
• Itching around the rectum.
• Weak, peeling, and cracked fingernails.
• Dilated blood vessels in the cheeks and nose (in non-alcoholics).
• Acne.
• Iron deficiency.
• Chronic intestinal parasites or abnormal flora.
• Undigested food in stool.
• Chronic candida infections.
• Upper digestive tract gassiness.

The following diseases are associated with low gastric acidity:

• Addison’s disease.
• Asthma.
• Celiac disease.
• Chronic autoimmune disorders.
• Chronic hives.
• Dermatitis herpetiformis (herpes).
• Diabetes.
• Eczema.
• Gallbladder disease.
• Graves disease.
• Hepatitis.
• Hyper and Hypothyroidism.
• Lupus erythematosus.
• Myasthenia gravis.
• Osteoporosis.
• Pernicious anemia.
• Psoriasis.
• Rheumatoid arthritis.
• Rosacea.
• Sjogren’s syndrome.
• Thyrotoxicosis.
• Vitiligo.

GERD/ Acid Indigestion and Hypochlorydia. 

Acid indigestion may also occur from too much stomach acid. However, this is rare it is most likely a regulatory issue in the physiology of digestion. Under normal conditions, the parietal cells of the stomach make HCl at a pH of 0.8. this
extreme acidity is normal physiology. A hyperacidic condition usually indicates that the gastric mucosa has lost the ability to handle normal amounts of gastric acid and therefore, is compromising the protective function.

CT genotypes (HTR2A gene) are more prevalent in gastroesophageal reflux disease (GERD) patients, relative to healthy controls.

Clinical considerations:

• Gastric or duodenal ulcers and gastritis may result, over time, from too little stomach acid.

2. Gastritis

Causes:

• Nonsteriodal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Advil, Motrin, others) and naproxen (Aleve) can cause damage to the protective lining of the stomach.
•  Alcohol use: Alcohol can irritate and erode the stomach lining.
• Stress.
• Bile reflux disease.

Signs and symptoms of chronic gastritis:

• Frequent stools or normal stool frequency.
• Weak appetite.
• Epigastric pain that becomes worse or better with eating.
• Unexplained nausea.
• Unexplained vomiting.
• Fever.
• Blood in the stool (end stage).
• Vomiting blood (end stage).
• Bloating.
• Belching.
• Hiccups.
• Low tolerance to spicy foods.
• Weight loss.
• A feeling of fullness after a meal.

3. Helicobacter pylori Infection

H.pylori is the bacterium that causes peptic ulcer disease. It can be detected in approximately 90% of individuals with peptic ulcers. There is a strong association between H.pylori infection and gastric cancer. It is estimated that 50% of the world’s population is infected with H.pylori.

Mode of transmission:

• Oral to oral.
• Fecal to oral.
• Family inter-infection (Note: Asymptomatic family members may need to be treated to stop transmission).

Laboratory testing.

• H.pylori serology.
• 90% specificity and sensitivity (IgG).
• Urea breath test (carbon 13).
• Based on products created when urea is split by the H.pylori.
• Drinks with urea labelled with a carbon 13 isotope, is ingested by the patient.
• The breath is measured for the carbon 13. If the concentration is high, possible H.pylori infection is suspected.
• H.pylori fecal antigen test.
• Based on monoclonal antibody immunochromatography. Specificity 98% Sensitivity 94%.
• Biopsy.
• Histology.
• Culture.
• Rapid urease test.

Note, that although the A allele in the rs492602 or the FUT 2 gene makes it easier for your gut to colonise Bifidobacterium, at the same time it increases the risk for H. Pylori infections.

4. Pancreatic Insufficiency

The signs of pancreatic insufficiency include gas, indigestion, bloating, discomfort, undigested food in our stools, undigested fat in our stools, and food sensitivities.

It is common in people with candidiasis or parasite infections and is an
underlying cause of hypoglycemia. Pancreatic insufficiency also increases with age. People with pancreatitis and cystic fibrosis have pancreatic insufficiency.

Stool testing with the comprehensive digestive stool analysis, provides an indirect measure of pancreatic function by measuring chymotrypsin, or pancreatic Elastase, and by measuring how well meats and vegetables are digested.

Causes of pancreatic insufficiency are stress, (mental and physical), nutritional deficiencies, poor diet, eating only cooked foods, exposure to radiation or toxins, hereditary weaknesses, drugs, and infections.

3. Dysbiosis

The mammalian immune system which is designed to control microorganisms is also controlled by microorganisms. 

Symbiotic Microflora Functions in the Gut

Metabolic Activities:

Microflora ferments non-digestible dietary residue releasing SCFAs and vitamin K.

Trophic Activities:

SCFAs produced by microflora control epithelial cell proliferation and differentiation in the colon (to protect against the development of neoplasia).

Protective Activities:

The barrier effect: resident bacteria provide resistance to colonisation by potentially pathogenic microbes.

Dysbiosis (also called dysbacteriosis) is the condition of having microbial imbalances on or within the body.

Dysbiosis is most prominent in the digestive tract but can also occur on any
exposed surface or mucous membrane such as the skin, vagina, lungs, nose, sinuses, ears, nails, or eyes.

Dysbiosis in one patient may present with dermatitis; the same microbial imbalance in another patient can present as peripheral neuropathy or inflammatory arthritis.

Yeast Infections (Candida sp.)

Candida are normal inhabitants of the gastrointestinal tract and are present in 40 -65 % of the human population with no harmful effects. However, in conditions of overgrowth, various Candida sp. are most commonly found as the causal
agents of opportunistic fungal infections.

Causes:

• Antibiotic use (main cause).
• High intake of sugar, milk, other dairy products and foods containing a high concentration of yeast or mold.
• Hypochlorhydria.
• Food allergies.
• Depressed immune system.
• Altered bowel flora.

Symptoms/conditions

• Gastric pain.
• Nausea and vomiting.
• Gas and bloating.
• Altered fecal transit time.
• Intestinal permeability.
• Imbalance in gut microflora.
• Opportunistic bacterial infection.
• Esophagus is the most common site of infection, followed by the stomach, then small and large bowel.
• 15% develop systemic candidiasis.
• May be associated with autistic spectrum disorders.

Extra-intestinal symptoms/conditions

• Chronic fatigue.
• Vaginal yeast infections.
• Depression.
• Irritability.
• Chemical sensitivity.
• Eczema, psoriasis.

Pathogenic bacteria:

Clostridum difficile

Causes:

• Suspect recent antibiotic use, especially the cephalosporin’s, ampicillin/amoxicillin, and clindamycin.
• Nosocomial.
• Advanced age.
• Fecal-oral colonization.

Symptoms/conditions

• Asymptomatic carrier.
• Cramping, lower abdominal pain, fever and diarrhoea, usually decreased once antibiotics are stopped, though can continue for up to 4 weeks.
• Pseydomembranous colitis.
• Cognitive and mental decline.

According to Dr. Yasko the A allele on this position of the ACAT1 gene, will predispose one to a greater chance of contracting Clostridium difficile infection.

Campylobacter sp

Causes: 

•  Contaminated animal food sources.
• Hydrochloric acid insufficiency.
• Secretary IgA deficiency.

Symptoms/conditions

• Abrupt influenza-like symptoms are common, including headache and malaise.
• GI symptoms include abdominal pain, nausea and vomiting, diarrhoea.
• Associated with reactive arthritis.

Entero hemorrhagic Escherichia coli (EHEC)

Causes

• Contaminated food (under cooked meat, raw milk, unpasteurised apple juice, water, and lettuce).

Symptoms

• Severe abdominal cramping, watery or bloody diarrhoea and vomiting.
• Hemorrhagic colitis (up to 10 of cases).

Opportunistic Bacterial Infections

Causes

• Low predominant bacteria.
• Pathogen or parasite infection.
• Poor diet.
• Antibiotic use.
• Lowered gut immunity.
• Symptoms/conditions.
• Asymptomatic.
• Diarrhoea.
• Constipation.
• Bloating/gas.
• Myalgia.
• Fatigue.
• Headaches.
• Autoimmunity:
  – Reactive arthritis: Salmonella sp.; Yersinia sp; Klebsiella sp.
  – General molecular mimicry mechanism: Morganella, Proteus and possibly Pseudomonas
  – Hashimoto Thyroiditis and Grave disease: Yersinia enterocolitica

Low Commensal (Good) Bacteria

Usually discovered on stool analysis.

Causes:

• Antibiotic.
• Diarrhoea.
• Imbalanced diet.

Symptoms/conditions

• Irritable bowel syndrome.
• Food intolerance.
• Increased likelihood of acquiring opportunistic and pathogenic organisms.

Variations in the FUT2 gene are particularly connected to a lesser population of the Bifidobacterium species.

PON1 gene protects against bacterial infection by destroying the bacterial signaling molecules that cause gram-negative bacteria to invade human tissue and form colonies. The T (minor) allele is associated with decreased levels of PON1 protein in the blood. TT genotype of this variant is usually associated with decreased blood levels of PON1.

Secretory IgA (sIgA): Predominant immunoglobulin released onto the surface of the GI mucosa.

It binds to and neutralises microbes and other antigens before they can
cross the mucosal barrier. Your genetic Variant Report has an entire section dedicated to genetic variants connected to IgA secretion. 

 

Small intestinal bacterial overgrowth
(SIBO) – tbc

4. Cholelithiasis

The combination of a ‘Western Diet’ high in saturated fats and a sedentary lifestyle in a population that is generally overweight creates an environment prone to gallstone formation. Formation of gallstones is the result of three factors:

one: supersaturation of bile with cholesterol,

two: a decrease in bile salts that act to dissolve the cholesterol vesicles, and

three: stasis of bile flow.

Conditions that may increase the risk: 

• Estrogen.
• Obesity.
• Cholesterol rich diet (The Diet and Nutrition section of your Variant Report also has a section related to cholesterol metabolism).

5. Parasitic Infections

Common Parasitic Infections

• Cryptosporidium species.
• Entamoeba histolytica.
• Giardia lamblia.
• Entamoeba coli and Endolimax
  nana.
• Entamoeba hartmani.
• Dientamoeba fragilis.
• Amebiasis (Entamoeba histolytica).
• Ascariasis (Round worm).
• Babesiosis.
• Cryptosporidiosis.
• Giardiasis.
• Hookworm.
• Schistosomiasis.
• Tapeworm.
• Toxoplasmosis.

Signs and Symptoms 

• IBS.
• Abdominal pain and cramping.
• Excessive flatulence.
• Foul smelling stools.
• Greasy stools.
• Malabsorption.
• Weight loss.
• Poor appetite.
• Indigestion.
• Headaches.
• Fatigue.
• Fever.
• Increased intestinal
  permeability.
• Food allergies.
• Hives.
• Gastritis.

Looking for Parasites

• O&P

– traditional method, well established,
– Individual samples,
– Pooled samples,

• EIA’s (most common)

– G. lamblia,
– Cryptosporidium,
– E. histolytica,

• DNA testing– New method

– Detects living and dead organisms,
– Detects anaerobes,

 

6. Gut Permeability

The small intestine has the paradoxical dual function of being a digestive/absorptive organ as well as a barrier to permeation of toxic compounds and macromolecules. Either one of these functions may be disrupted by various
mechanisms, resulting in local as well as systemic problems.

Increased permeability of the intestinal mucosal barrier appears to correlate with a number of frequently seen clinical disorders, while decreased permeability appears as a fundamental cause of malnutrition, Malabsorption and failure to thrive.

Increases in permeability have consistently been reported with small bowel inflammation. Permeability studies show Crohn’s disease to be more extensive than sometimes apparent using macroscopic approaches. When patients with
Crohn’s disease were placed on an elemental diet, their permeability improved significantly, coinciding with marked clinical improvement.

The concept that the underlying aetiology of inflammatory arthritis (including rheumatoid arthritis) is related to pathology in the gut has become more accepted by researchers. All material that traverses the mucosa is inspected by the immune system, and it is here that the immune system may have its greatest antigenic exposure. Increased gut permeability can permit exogenous antigens to enter the systemic circulation. If the antibodies generated towards gut antigens cross-react with the body’s own immunologically similar tissues, the resulting process may manifest itself as an autoimmune disease.

Factors, Symptoms and Diseases Associated with Dysbiosis and Intestinal Hyperpermeability:

Contributing Factors Diseases

• Alcohol abuse.
• Corticosteroid use.
• NSAIDs use.
• Excessive stress.
• Nutrient insufficiencies.
• Gastrointestinal infections.
• Food reactions.
• Improper fasting.

Symptoms

• Abdominal distention.
• Diarrhoea.
• Constipation.
• Abdominal pain.
• Food intolerances.
• Skin rashes.
• Poor exercise tolerance.
• Shortness of breath.
• Cognitive deficits.
• Fatigue and malaise.
• Arthralgia.
• Myalgia.
• Fevers of unknown origin.

Diseases

• Inflammatory bowel disease.
• Irritable bowel syndrome.
• Celiac disease.
• Infectious enterocolitis.
• Cystic fibrosis.
• Chronic fatigue immune deficiency syndrome.
• Acne.
• Eczema.
• Psoriasis.
• Urticaria.
• Dermatitis herpetiformis.
• Autism.
• Childhood hyperactivity.
• Spondyloarthropathies.
• Pancreatic insufficiency.
• HIV infection.
• Neoplasia treated with cytotoxic drugs.
• Hepatic dysfunction.
• Alcoholism.
• Environmental illness.

In our Variant Reports, the Gut permeability sections feature two variants of the PEMT gene. PEMT (also known as MUC1) encodes a protein called mucin 1. This protein helps make up mucus, which lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs and tissues. The T allele of the rs7946  means lower levels of the PEMT protein.

 

7. IBS

IBS is the one most common gastrointestinal disease seen in clinical practice. It has been characterised as a functional bowel disorder.

Rome II Criteria for Diagnosis of IBS:

Presence of abdominal pain or discomfort for at least 12 weeks, which need not be consecutive, in the preceding 12 months, with at least two of three features:
1. Relief of symptoms with defecation and/or
2. Onset associated with a change in frequency of stool and/or
3. Onset associated with a change in form (appearance) of stool

Recommended advanced functional laboratory testing

• Stool analysis.
• Allergy testing – food/environmental.
• Organic acid test.
• Intestinal Hyperpermeability test.
• Heidelberg capsule.
• Gastro test.
• Nutritional blood test.
• Methylmalonic acid.
• Nutritional homocysteine.
• Serum B12.
• Vitamin D 25-OH.

This genetic variation of the TNFSF1 gene increases risk of Inflammatory Bowel Disease.

The T allele on this position of the HTR2A gene has been associated with increased risk for irritable bowel syndrome.

 

8. IBD

The term inflammatory bowel disease (IBD) is used to describe two chronic relapsing and remitting diseases, ulcerative colitis (UC) and Crohn’s disease (CD).
A precipitating infectious source has been sought without success. Animal models, supported by a growing body of clinical research, suggest that comensal gastrointestinal flora may, in part, be responsible.

Explore the genetic connection between the FUT2 gene variant and IBD here. 

 

SUMMARY:

These are necessary for healthy gut maintenance:

• Proper nutritional substrates, micronutrients, and phytonutrients for:
– maintenance of commensal flora,
– immune modulation, and
– repair and regeneration
• Proper mastication,
• Adequate digestive juices, enzymes, and pH,
• Intact intestinal epithelial barrier function,
• Balanced host-bacteria ecology,
• Autonomic balance,

Below are factors which contribute to poor GI system health:

• Dehydration,
• Poor diet,
• Interaction of medications,
•  Infections,
• Toxins (metals, molds, foods),
• Inadequate digestive enzymes & stomach acid,
• Imbalanced ecology,
• Impaired intestinal permeability,
• Altered neuroendocrine balance and autonomic function,

Patients are best served if we observe the inter-relationships between:

• Digestion & Absorption,
• Intestinal Permeability,
• Gastrointestinal Microbiota (all types),
• Immune Modulation & Inflammation,
• Nervous System,

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References
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CCN, Ernest B. Hawkins, RPh, MS, Ross Pelton, RPh, PdD, DDN, Nancy Ashbrook-Willis, BA, JD
2. Metametrix Handbook, Clinical Reference Manual, 2009 Metametrix Institute
3. Klaire Laboratories, Inc. 10439 Double R Blvd., Reno, NV 89521
4. Digestive Wellness, 3rd ed, Elizabeth Lipski, PhD, CCN
5. Natural Medicine Instructions for Patients, 2002, Lara Pizzorno, Joseph E. Pizzorno, Jr., Michael T. Murray
6. Laboratory Evaluations for Integrative and Functional Medicine, 2nd ed, Richard S. Lord and J. Alexander Bralley
7. Applied Clinical Nutrition with Biotics Research Products, Nutritional Protocols, 2005, Michael Owen, D.C.
8. Integrative Medicine, 2003, David Rakel, M.D.
9. http://emedicine.medscape.com/article/176938
10. American Journal of Gastroenterology, American College of Gastroenterology Guideline, 2007 article on The
Management of Helicobacter Pylori Infection