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Increased Intestinal Permeability (Leaky Gut)

Close-up Slice of a Small Intestinal Villus Showing How Enterocytes Appear Tightly Lining the Entire Outside Surface Of A Villus. Courtesy Cleo Libonati

What Is Increased Intestinal Permeability?

[dropcap]I[/dropcap]ncreased intestinal permeability is characterized by dysfunctional intestinal permeability (leakiness) allowing for the penetration of harmful entities from the gut into the bloodstream such as undigested proteins and microbes. The popular name is “leaky gut.”

Q: Why does intestinal permeability increase?

A: Intestinal permeability is an essential function of the small intestinal mucosal lining by which wanted substances such as properly digested foodstuffs are allowed to permeate through the lining to enter the body via the bloodstream and lymphatics. At the same time unwanted substances are kept out.

The mucosal lining is one cell thick and makes up the surface between the digested foodstuffs inside the hollow of the intestine and the underlying tissues.

The mucosal lining is covered by millions of microscopic finger-like structures called villi that project toward the inside of the intestine giving the appearance of a shag rug.

Each one, called a villus, contains a capillary bringing blood to absorb nutrients, a vein to take away nutrients, and a lacteal to absorb and take away digested fat. Its wall is made up of a single layer of tightly connecting cells, called enterocytes.

This single layer of cells separates the contents of our small intestine from the lamina propria (underlying tissues of the small intestine) and the rest of our body. Breaching of this single layer of cells by leakiness can expose lymphocytes (immune cells) located in the lamina propria to a myriad of microorganisms and food antigens, leading to immune reactions.1

To protect the body from unwanted substances, a gatekeeping barrier system operates to regulate the passage of nutrients, or permeation, through the surface mucosal lining. This system acts to seal the inside body from the gut.

The integrity of intestinal permeability is determined by interactions among several barrier components including the unstirred water layer, mucosal surface hydrophobicity, the surface mucous coat, and cell factors (especially tight junctions).

Tight junctions hold cells tightly together side-by-side to prevent unwanted substances from passing through the lining. Tight junctions are complex structures comprising over 50 proteins, such as the claudin proteins which are considered to be the structural backbone of tight junctions.

Tight junctions include a series of special proteins forming fibrils (springy like proteins) that cross the plasma membrane and interact with proteins in the adjoining cells. Tight junctions are regulated by the protein zonulin.2

If zonulin deregulates from the action of substances such as gliadin (gluten in wheat) and bacteria, the tight junction barrier fails which results in increased intestinal permeability. Dysfunction of the barrier system allows unwanted substances to enter the body where they are damaging to many tissues.

Tight junction dysfunction has been shown to be a part of certain autoimmune diseases such as celiac disease, type I diabetes mellitus, multiple sclerosis, and rheumatoid arthritis. Other diseases associated are cancer, allergies, and infections.3

Important gastrointestinal infections that cause leaky gut include rotavirus, parasites, pathogenic bacteria (escherichia coli, clostridium difficile), and mycotoxins produced by fungi found in stored grain and dried fruit.4

Fortunately, the presence of some commensal (friendly intestinal bacteria) and probiotic strains leads to an increase in tight junctions  proteins at the cell boundaries and in some cases prevents or reverses the adverse effects of pathogens, food and stress. Various dietary components are also known to regulate epithelial permeability by modifying expression and localization of  tight junctions proteins.2

What Is Increased Intestinal Permeability In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Fahardi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003; 18: 479-497. [↩]
  2. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr. 2011 May;141(5):769-76. doi: 10.3945/jn.110.135657. [↩] [↩]
  3. Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. January 2011Vol. 91no. 151-175DOI: 10.1152/physrev.00003.2008 [↩]
  4. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩]

Constipation, Chronic

Constipation in a young child as seen on X-ray. Lowest circle shows hard feces in the pelvis. Source, James Heilman, MD.

What Is Chronic Constipation?

[dropcap]C[/dropcap]hronic constipation is an intestinal motility disorder characterized by abnormal stool formation, consistency, and evacuation.

Motility disorder means the normal rhythmic movement of intestinal muscles, called peristalsis, that moves food matter through the gut is hampered or dysfunctional.

Studies show that methane gas present in the colon induces constipation by delaying transit time, which is the time it takes for stool to pass through the colon.

Researchers investigating the relationship between methane and constipation found that methane positivity was detected in 75% of patients with slow transit, 44% of patients with normal transit and and 28% of the patients who were controls. However, methane positivity was not related with stool consistency.1

Other researchers investigating the total amount of methane produced found that there was significantly more methane production in patients with constipation (21.1 ppm vs. 6.1 ppm, respectively) than in controls without constipation.2

Q. How does methane get into the colon?

A. Methane is produced in the colon by intestinal methanogens (microbes) that metabolize hydrogen, one of the end products of normal anaerobic (meaning without oxygen) bacterial fermentation.  Fermentation of the undigested starchy part of carbohydrates produces hydrogen in the intestine which is the substrate (food) for methane production by intestinal methanogens.

Hydrogen and methane are excreted in the flatus and in breath giving the opportunity to indirectly measure their production using breath testing. Methane is detected in 30%-50% of the healthy adult population worldwide.3

Other common causes of constipation include not getting enough exercise, not drinking enough fluids, not eating enough fiber in the diet, not eating foods that supply microbes needed by the colon (probiotics), not eating foods that nourish the good microbe population (prebiotics) and supply minerals needed for healthy movement of stool, and food sensitivities. Too much cows milk is a common cause of stool that forms into balls.

Who is Affected in the General Population? Chronic constipation is a remarkably common and costly condition that can negatively impact the quality of life and result in a major social and economic burden. Based on the definition, either self-reported or using Rome criteria, chronic constipation can affect up to 27% of the population. There is strong evidence that constipation occurs more frequently in women.4

What Is Chronic Constipation In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Triantafyllou K, Chang C, Pimentel M. Methanogens, Methane and Gastrointestinal Motility. J Neurogastroenterol Motil. 2014 Jan;20(1):31-40. Epub 2013 Dec 30. [↩]
  2. Triantafyllou K, Chang C, Pimentel M. Methanogens, Methane and Gastrointestinal Motility. J Neurogastroenterol Motil. 2014 Jan;20(1):31-40. Epub 2013 Dec 30. [↩]
  3. Triantafyllou K, Chang C, Pimentel M. Methanogens, Methane and Gastrointestinal Motility. J Neurogastroenterol Motil. 2014 Jan;20(1):31-40. Epub 2013 Dec 30. [↩]
  4. Sanchez MI, Bercik P. Epidemiology and burden of chronic constipation. Can J Gastroenterol. 2011 Oct;25 Suppl B:11B-15B. [↩]

Systemic Lupus Erythematosus 

Image showing butterfly rash of SLE. Courtesy JAMA.
Image showing butterfly rash typical of SLE. Courtesy JAMA.

What Is Systemic Lupus Erythematosus?

[dropcap]S[/dropcap]ystemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that is characterized by involvement of multiple organs due to the production of antibodies to components of the cell nucleus.1 SLE has an unpredictable course of acute flare-ups and remissions.

Severity depends on the extent of organs affected with skin and nail involvement, called discoid lupus, being the least serious and inflammmation of the kidney, called lupus nephritis, being the worst.

Nevetheless, a classic presentation is development of a rash over the cheeks and nose that resembles a butterfy with wings spread hence the name “butterfly rash.”

Symptoms are many and varied depending on the tissues affected and are often not specific, for example hair loss has a variety of causes. Symptoms can be confused by co-existence with other autoimmune disease such as Sjogren’s syndrome.

Systemic lupus erythematosus should be managed by a specialist. Symptoms can be controlled with steroid therapy, but this disease can be a cause of premature death  mainly from active disease, organ failure (e.g., kidneys), infection, or cardiovascular disease from accelerated atherosclerosis.

Certain common medicines known to cause drug-induced lupus are:

  • Isoniazid
  • Hydralazine
  • Procainamide

Other less common drugs may also cause the condition. These may include:

  • Anti-seizure medications
  • Capoten
  • Chlorpromazine
  • Etanercept
  • Infliximab
  • Methyldopa
  • Minocycline
  • Penicillamine
  • Quinidine
  • Sulfasalazine

Symptoms tend to occur after taking the drug for at least 3 to 6 months.2

Although there is a strong familial aggregation, the disease is relatively uncommon and most cases are sporadic.1 According to the Center for Diseases (CDC), lupus most commonly affects women of childbearing age but also occurs in infants, children, adolescents, and men with peak occurrence between ages 15 and 40. Blacks (and possibly Hispanics, Asians, and Native Americans) are affected more than Whites.

What Is Systemic Lupus Erythematosus In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. http://www.cdc.gov/arthritis/basics/lupus.htm [↩] [↩]
  2. www.nlm.nih.gov/medlineplus/ency/article/000446.htm [↩]

Sjögren’s Syndrome 

Testing the Eyes for Sjogren's Syndrome.
Testing the Eye for Tear Production (L) and Damage to Conjunctiva from Dryness (R).

What Is Sjögren’s Syndrome?

[dropcap]S[/dropcap]jögren’s syndrome is a systemic inflammatory autoimmune disease with a chronic, progressive course that primarily attacks the lacrimal glands of the eye and the salivary glands of the mouth, which are exocrine glands. Exocrine glands secrete the substances they produce through a duct.

Sjögren’s syndrome is ordinarily characterized by dysfunction of the lacrimal glands to produce tears causing dry eye and the salivary glands to produce saliva causing dry mouth, but is not limited by or to these features.

Besides involvement of these exocrine glands, there may be involvement of other parts of the body, termed extraglandular, which may be more severe than eye or mouth features.

There is not yet agreement on classifying Sjögren’s syndrome. Primary and secondary are the two forms generally accepted.1 Both forms can cause mild to severe disease, called the spectrum:

  • Primary Sjögren syndrome. Disease occurs without involvement of other linked autoimmune disorders. In addition to the eyes and mouth, the nose, throat and skin may also be affected and joints, lungs, kidneys, blood vessels, digestive organs and nerves as well.2 Systemic manifestations (other than eyes and mouth) concern a third of patients, including lymphoma in 5% of the patients.3
  • Secondary Sjögren’s syndrome. Disease complicates other autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, primary biliary cirrhosis, and celiac disease.

Diagnosis  of Sjögren’s syndrome is made by most doctors based on Schimer’s test for tears and unstimulated whole salivary flow to assess objective eye and oral involvement, since these are the tests most physicians use in clinical practice.4 Specific antibody tests would be  positive for anti-Ro (SSA)/anti-La (SSB) autoantibodies. Sjögren’s syndrome should also be considered when extraglandular manifestations such as vasculitis, polyneuropathy or arthritis occur, even when the patients do not complain of dry eyes and mouth.5

There is no cure for Sjögren’s syndrome. Treatment is aimed to diminish symptoms. For example, steroids and Ibupropen are used to decrease inflammation and pain in joints. Artificial tears and ointments are used for dry eye.

Most people who develop Sjogren’s syndrome are older than 40 years. Nine of ten people with Sjögren’s syndrome are women.2

What Is Sjögren’s Syndrome In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Huang YF, Cheng Q, Jiang CM, An S, Xiao L, Gou YC, Yu WJ, Lei L, Chen QM, Wang Y, Wang J. The immune factors involved in the pathogenesis, diagnosis, and treatment of Sjogren’s syndrome. Clin Dev Immunol. 2013;2013:160491. doi: 10.1155/2013/160491. Epub 2013 Jul 9. [↩]
  2. nlm.nih.gov [↩] [↩]
  3. Fazaa A, Bourcier T, Chatelus E, Sordet C, Theulin A, Sibilia J, Gottenberg JE. Classification criteria and treatment modalities in primary Sjögren’s syndrome. Expert Rev Clin Immunol. 2014 Apr;10(4):543-51. doi: 10.1586/1744666X.2014.897230. [↩]
  4. Cornec D, Saraux A, Cochener B, Pers JO, Jousse-Joulin S, Renaudineau Y, Marhadour T, Devauchelle-Pensec V. Level of agreement between 2002 American-European Consensus Group and 2012 American College of Rheumatology classification criteria for Sjogren’s syndrome and reasons for discrepancies. Arthritis Res Ther. 2014 Mar 19;16(2):R74. [↩]
  5. Witte T. Pathogenesis and diagnosis of Sjögren’s syndrome. Z  Rheumatol. 2010 Feb;69(1):50-6. doi: 10.1007/s00393-009-0519-2. [↩]

Intrauterine Growth Retardation (Failure to Grow Normally Before Birth)

intrauterine growth retardation gluten free
The twin on the right is much small than his brother on the left who has normal growth.

What Is Intrauterine Growth Retardation?

[dropcap]I[/dropcap]ntrauterine growth retardation (IUGR) is a fetal development abnormality characterized by failure to grow normally for gestational period. Specifically, it means the developing baby weighs less than 90% of other babies at the same age.

Intrauterine growth retardation puts the baby at increased risk for complications such as premature birth or that the baby will die inside the womb before birth.1

Intrauterine growth restriction  may be suspected if the size of the pregnant woman’s uterus is small. The condition is usually confirmed by ultrasound. Further tests may be needed to screen for infection or genetic problems if intrauterine growth retardation is suspected.

Q: Why would a baby not grow normally during pregnancy? A: An unborn baby cannot grow normally  if it does not obtain adequate oxygen and nutrition delivered through the placenta from the mother. Factors that impede adequate delivery of nutrition include:

  • Poor placenta placement. Conditions that limit or interfere with space for nutrient and oxygen absorption between the placenta and the uterine wall include 1) low attachment of the placenta near or over the cervix where maternal blood supply is poor, 2) pulling away or bleeding between the placenta and uterine wall, 3) multiple placentas (from multiple babies) sharing the uterine wall may limit blood supply to one or more of the fetuses, and 4) the presence of an hydatid mole,  (non-fertilized egg growing wildly), tumor or fibroids taking up space or growing under or into the placenta. 
  • Chromosomal abnormalities in the fetus. Conditions such as trisomy 22  have early onset  of  intrauterine growth retardation  in pregnancy. 
  • Poor health of the mother. These factors include 1) anemia which impairs the ability of the mother’s blood to deliver adequate oxygen, 2) preeclampsia which interferes with placenta function, 3) diabetes which impairs proper supply of energy, 4) kidney disease, 5) poor diet, 6) malabsorption, 7) high blood pressure or heart disease, 8) clotting disorders, and 9) toxins and infections during pregnancy that may harm the developing baby such as rubella, cytomegalovirus, toxoplasmosis, and syphilis. 
  • Risk factors in the mother. Any of the following may contribute to intrauterine growth retardation:1
  • Alcohol abuse.
  • Drug addiction.
  • Smoking.

What Is Intrauterine Growth Retardation In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. http://www.nlm.nih.gov/medlineplus/ency/article/001500.htm [↩] [↩]

Obstetrical Complications

Inefficient Labor May Necessitate Ceasarian Section to Save the Baby.
Inefficient Labor May Necessitate Ceasarian Section to Save the Baby. Courtesy Wikipedia.org

What Are Obstetrical Complications?

[dropcap]O[/dropcap]bstetrical complications are reproductive disorders during pregnancy, labor and delivery that endanger the mother and unborn infant.

Complications may result from prolonged constipation, malnutriton, hormonal imbalance, infection, systemic disease such as diabetes, obesity, tumors of the uterus, medication adverse effects, drug abuse, smoking, and alcohol abuse.

What Are Obstetrical Complications In Celiac Disease and/or Gluten Sensitivity?

Dementia

DementiaWhat Is Dementia?

[dropcap]D[/dropcap]ementia is the term used to describe a group of symptoms that show significant deterioration of an individual’s intellectual and social abilities.

The deterioration in intellectual function is progressive and is characterized by memory and cognitive impairment involving deficits in reasoning, judgment, abstract thought, comprehension, learning, use of language, and task execution.

Some types of dementia can be reversed,  while most types of dementia are degenerative or nonreversible.

Q: What causes dementia?

A: There are  many differing causes of dementia.  Here are some causes according to nonreversible and reversible:

  • Nonreversible dementia may not be turned back due to these conditions:
  • Alzheimer’s disease is the most common type of degenerative dementia caused by abnormal protein structures in certain areas of the brain. 
  • Lewy body disease is a leading cause of dementia in elderly adults.
  • Vascular dementia due to many small strokes.
  • Medical conditions: Huntington’s disease, multiple sclerosis, infections that can affect the brain, such as HIV/AIDS and Lyme disease, Parkinson’s disease, Pick’s disease, and progressive supranuclear palsy.
  • Reversible dementia may be stopped or reversed if these conditions are found soon enough:
  • Brain injury.
  • Brain tumors.
  • Chronic alcohol abuse.
  • Changes in blood sugar, sodium, and calcium levels.
  • Changes that can occur with celiac disease, diabetes, thyroid disease, and other metabolic disorders.
  • Nutritional deficiencies.
  • Use of certain medications, including cimetadine and some cholesterol-lowering medications.1

What Is Dementia In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001748/ [↩]

Muscle Spasm And Muscle Cramps 

Muscle spasm and cramping in celiac disease and gluten sensitivity symptomWhat Are Muscle Spasm, Muscle Cramps?

[dropcap]M[/dropcap]uscle spasm and muscle cramps are  disorders of muscle function caused by painful involuntary contractions of affected skeletal muscles characterized by limited movement.

Q: What is the difference between muscle spasm and cramps?

A: Cramps are stronger and more painful than spasms, occurring while the muscle is in its most shortened state.

Skeletal muscles are those that move the body skeleton to do work as we choose. Examples are muscles that move the mouth, arms,  hands, legs, and feet.

What Are Muscle Spasm, Muscle Cramps In Celiac Disease and/or Gluten Sensitivity?

Weight Gain, Unexplained

Obesity_001_[1]

What Is Unexplained Weight Gain?

[dropcap]U[/dropcap]nexplained weight gain is characterized by increased body mass due to excess fat accumulation that is not desired by the individual.

A body mass index (BMI) of 25 to 30 signifies being overweight.

What Is Unexplained Weight Gain In Celiac Disease and/or Gluten Sensitivity?

Headache (Emicrania)

headache gluten celiac disease symptomWhat Is Headache Or Emicrania?

[dropcap]E[/dropcap]micrania is a headache resulting from stimulation of, or traction of, or pressure on any of the pain sensitive structures of the head characterized by pain felt anywhere in the head.

In addition to gluten sensitivity and nutritional deficiencies, there are many causes of headache including cardiac, cerebral, vascular, psychiatric, metabolic, and neurologic diseases. Recent studies have highlighted that obesity is significantly associated with headache and disability in adults. This rule also applies to children.1

What Is Headache In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Laino D, Vitaliti G, Parisi P,   et. al. Headache, migraine and obesity: an overview on plausible links. J Biol Regul Homeost Agents. 2016 Apr-Jun;30(2):333-8. [↩]