April 11, 2017

The role of actin autoimmunity in intestinal permeability

By Aaron Mello, CNTP, MNT

Actin is a protein that is best known for its role in muscle contraction, where it works as a team with myosin. In addition, actin also plays a key role in the structure and function of the small intestine. Because of actin’s contribution to the integrity of the intestinal wall, autoimmunity against this protein may also play a role in intestinal permeability, aka leaky gut.

actin and myosin

Actin and myosin heads make smooth muscle contraction possible

What is actin?

Actin is a protein that is utilized in many functions in the body. Actin plays two primary roles in intestinal anatomy.

Actin’s first role in the small intestine is in the microvilli, hairlike protrusions that increase surface area in the small intestine. They increase the ability of the small intestine to absorb nutrients across the intestinal lining and into the bloodstream. More surface area means more contact with the chyme and an increased ability to absorb nutrients. In the microvilli, actin is used to make the microfilaments which provide structure to these microscopic microvilli. The extremely fine actin microfilaments provide structure to the hairlike filaments protruding into the lumen of the small intestine, reaching out to absorb nutrients from chyme.

microvilli in small intestine

Microvilli in the small intestine

Actin is also involved in many other functions microvilli physiology, in addition to the structure itself. Some of these roles include cell division and locomotion, transporting embryonic cells, allowing white blood cells to leak into tissue to fight infection, and assisting skin cells in wound healing. In many ways, the health of microvilli cells are dependent upon actin.

Actin also helps adhere individual microvilli to each other in order to create an impermeable intestinal membrane. When this membrane becomes permeable, also known as leaky gut, the junctions between microvilli become separated and this compromises the integrity of the gut wall. This allows partially digested food particles to enter the blood stream, which is implicated in multiple types of autoimmune conditions, as well as food sensitivities.

Because actin is so important for the structure and function of the intestinal lining it is not surprising that problems with actin can contribute to intestinal permeability. Actin autoimmunity is thought to be a contributory factor in leaky gut because a breakdown of actin leads to degradation of the intestinal wall, allowing it to become permeable.

Other factors contributing to leaky gut

Leaky gut appears to have multiple causes. One common model for intestinal permeability involves tight junctions between the villi in the intestine, which in a healthy intestine create an impermeable membrane that lines the intestinal wall. A primary function of this imbermeable membrane is to contain partially digested foods in the lumen of the small intestine until they are broken down into small enough molecules to be transported across the intestinal wall by the microvilli.

Larger partially digested proteins in the blood appear to be a causative factor in many food sensitivities and autoimmune conditions, because these foreign proteins may trigger an immune response. Continued presence of these foreign proteins can result in a hyperimmune state that can lead to autoimmunity over time.

Tight junctions are not the only way epithelial cells are joined together to create an impermeable membrane. Adherens junctions are another type of junction that rely on actin microfilaments to form the adhesion belts that tie epithelial cells together. This may be another way actin autoimmunity may contribute to leaky gut. Actin that is subject to attack from the immune system may be unable to form strong adherens junctions.

Some substances and disorders that may contribute to leaky gut include include:

  • Gluten, gliadin and zonulin
  • Small intestine bacterial overgrowth (SIBO)
  • Dysbiosis
  • Yeast and bacterial overgrowths

Gluten, gliadin and zonulin

One of the best researched causes of intestinal permeability is the presence of zonulin, a hormone that regulates the tight junctions between cells in the intestinal lining. Zonulin is released in response to some bacteria, as well as gluten-containing foods. Like gluten, gliadin is another protein found in wheat that has been shown to cause zonulin to be released, leading to intestinal permeability. Gliadin also triggers celiac symptoms in people with celiac disease.

Small intestine bacterial overgrowth (SIBO)

SIBO is defined as an abnormally high number of bacteria in the small intestine, defined as “a bacterial population in the small intestine exceeding 105–106 organisms/mL.” Healthy populations are normally less than 103 organisms/mL.

Although SIBO is a common comorbidity with IBS and inflammation of the intestines, research does not appear to show a correlation between SIBO and intestinal permeability.

Dysbiosis

Dysbiosis can be a contributing factor to intestinal permeability. In dysbiosis, “unfriendly” bacteria take over the normal beneficial bacteria that inhabit the intestines. These probiotic bacteria help to digest food and synthesize nutrients. In contrast, the metabolic byproducts of pathogenic bacteria metabolism are toxins that irritate the intestinal lining. These toxic byproducts may contribute to intestinal permeability.

Yeast and Bacterial Overgrowths

In addition to bacterial overgrowths in the intestine which can lead to dysbiosis, yeast and fungi can proliferate out of control and cause dysbiotic inflammation as well. One of the most common overgrowths is candida, a yeast which normally inhabits the intestine in small quantities but is kept in check by probiotic bacteria. In candida overgrowth, the yeast takes over the intestine and commonly results in a telltale white coating on the tongue.

Another common overgrowth is clostridia difficile, or C. diff for short. This bacterial infection commonly occurs after the use of antibiotic medications, which can decimate the probiotic bacteria that help to keep C. diff in check. C. diff infections also commonly occur after prolonged hospital stays.

These overgrowths produce toxic metabolic byproducts that irritate and inflame the intestines, which can contribute to intestinal permeability as well as other disorders like Inflammatory Bowel Disease (IBD).

Testing for leaky gut

We commonly use the Wheat Zoomer test by Vibrant Wellness to evaluate intestinal permeability. Some of the many markers included in this comprehensive test include anti-actin IgG & IgA, as well as anti-zonulin antibodies. This can be used to evaluate whether autoimmunity against actin is present. Another good testing option is the Cyrex Array 3, which looks at many of the same markers.

These tests can help functional practitioners identify actin autoimmunity, as well as many other markers. Wheat Zoomer in particular provides a comprehensive snapshot of many different antibodies, including gliadin, transglutaminase, and many other markers. Other useful markers include LPS and Occludin, which will be covered in detail in a future post.

Recommendations to address leaky gut

  • Get a Wheat Zoomer test done (from Vibrant America) or a Cyrex Array 3 panel
  • Find a functional medicine practitioner and test for SIBO, parasites, yeast overgrowth, H. pylori and other gut markers
  • Remove GMO foods, highly processed foods, and foods with high pesticide residue levels
  • Get adequate amounts of the right kind of movement for your body
  • Manage stress with mindfulness practice and time in nature
  • Have fun! Take time to laugh with friends and replenish yourself

Other diseases and actin autoimmunity

Actin autoimmunity is well-established as a correlated factor in several disease. The most well-known link is in autoimmune hepatitis. Two antibodies are often present in autoimmune hepatitis, anti-actin antibody (AAA) and smooth muscle antibody (SMA). In fact, SMA is used as a diagnostic criterion for diagnosing autoimmune hepatitis.

SMA antibodies in particular are present in many disease, a number of which are autoimmune. IgG antibodies to SMA are found in 40-70% of chronic active hepatitis and autoimmune hepatitis and in 50% of primary biliary cirrhosis cases.

These two antibodies are also relevant to celiac disease. Both AAA and SMA are markers of intestinal damage in celiac. A 2005 study investigated in more detail the possible connections between AAA, SMA and celiac disease.

They found that “the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients… [and that] the presence of SMA seems to define a distinct subset of CD patients with a more severe clinical outcome.”

In conclusion

Actin autoimmunity plays a central role in several diseases and is even used as a marker in several cases, for example to determine the severity of intestinal damage in celiac disease. Based on its roles in the structure of the microvilli and the integrity of the intestinal wall it is clear how actin autoimmunity plays a strong role in intestinal permeability, and as a downstream consequence, other autoimmune diseases.

Future posts will explore these topics in more detail. Be sure to check back for those upcoming posts, which will go into more detail about:

  • Wheat Zoomer test and markers like LPS and Occludin
  • Cyrex Array 3
  • What markers on these tests indicate

References

Ventura, M.t., L. Polimeno, A.c. Amoruso, F. Gatti, E. Annoscia, M. Marinaro, E. Di Leo, M.g. Matino, R. Buquicchio, S. Bonini, A. Tursi, and A. Francavilla. “Intestinal Permeability in Patients with Adverse Reactions to Food.” Digestive and Liver Disease38.10 (2006): 732-36. Web.

Tortora, Gerard J., and Sandra Reynolds. Grabowski. Principles of Anatomy and Physiology. New York: HarperCollins College Pub., 1996. Print.

Dukowicz, Andrew C., Brian E. Lacy, and Gary M. Levine. “Small Intestinal Bacterial Overgrowth: A Comprehensive Review.” Gastroenterology & Hepatology 3.2 (2007): 112–122. Print.

Park, Jung Ho et al. “The Relationship between Small-Intestinal Bacterial Overgrowth and Intestinal Permeability in Patients with Irritable Bowel Syndrome.” Gut and Liver 3.3 (2009): 174–179. PMC. Web. 10 Apr. 2017.

Teixeira, Tatiana F.s., Maria Carmen Collado, Célia L.l.f. Ferreira, Josefina Bressan, and Maria Do Carmo G. Peluzio. “Potential Mechanisms for the Emerging Link between Obesity and Increased Intestinal Permeability.” Nutrition Research 32.9 (2012): 637-47. Web.

Aubert, Vincent, Isabelle Graf Pisler, and François Spertini. “Improved Diagnoses of Autoimmune Hepatitis Using an Anti-actin ELISA.” Journal of Clinical Laboratory Analysis 22.5 (2008): 340-45. Web.

Pedreira, Silvia C., Horacio Vazquez, Emilia Sugai, Sonia I. Niveloni, Edgardo G. Smecuol, Roberto Mazure, Daniel Flores, Eduardo Maurino, and Julio C. Bai. “Clinical Significance of Anti-smooth Muscle Antibody (SMA) Fluorescence in Patients with Celiac Disease.” Gastroenterology 118.4 (2000): n. pag. Web.

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