immune system

Also called hyperpermeable bowel, leaky gut syndrome is a condition that has a strong relationship to the immune system and the development of chronic disease.

Bella was losing weight uncontrollably after treatment for gastritis and small intestinal bacterial overgrowth. She had been treated with prednisone, vitamin E and folate for vomiting and diarrhea, but her weight continued to drop. Among other things, she was suspected to have leaky gut syndrome or hyperpermeable bowel, a disorder that affects digestive function, nutrient absorption and has a strong relationship with the immune system.

When we or our dogs eat, we want the digestive system to absorb all the good stuff while keeping out the potentially toxic, antigenic and pathogenic materials. How does the digestive system do this? The answer lies in the four levels of protection provided by the barrier system of the GI mucosal wall:

1. Mucus layer covering the microvilli
2. Tight junctions between epithelial cells
3. GALT-sIgA in the mucus of the glycocalyx
4. Probiotic species

The gastrointestinal tract has the greatest amount of surface area exposed to the environment of all three barrier systems in the body. In humans, the skin has less than ten square meters of surface area, whereas the lungs have about 140 square meters. The human gastrointestinal tract, however, has 320 square meters of surface area exposed to the environment. These surface area relationships are comparable in dogs.

Breaching the barrier

The GI mucosal barrier can be disturbed through gastrointestinal tract injury, exposure to toxins, or infection. Bacterial infections and endotoxins can injure the tight junctions holding intestinal mucosal cells together.

  • Bacterial overgrowth secondary to the inappropriate use of H2 blockers and antacids can lead to proximal gut colonization by pathogenic bacteria that are “attracted” to the more alkaline pH. Immuno-suppressed or protein-deficient patients can have decreased sIgA production, which impairs the immuno-protective value of this secretory immunoglobulin. sIgA is embedded in the mucus layer that overlies the mucosal epithelia.
  • The liver provides defensive activity both in terms of its phagocytic Kupffer cells, and its enzyme detoxification systems. It has a dual-phase system of detoxification. Hepatic enzymes decontaminate toxins and metabolic toxic by-products, and help degrade antigens and antigen/ antibody complexes. Kupffer cells play an important role in the GI immune system by removing bacteria, particulate matter and toxins. Compromised barrier function increases the total toxic load on the body by allowing ingested toxins and xenobiotics entry into the systemic circulation, bypassing the portal circulation, thus allowing these foreign substances to enter the body without modification by hepatic detoxification enzymes.
  • Prolonged fasting may do more harm than good in patients with challenged immune systems. “Bowel rest” for more than three days has been shown to cause deterioration of the enterocyte population, which can lead to atrophy of the mucosal surface, alterations in bowel permeability and an overall diminution of gastrointestinal immune function.
  • With disrupted barrier function, antigens and pathogens gain entrance into the systemic immune system. They first make contact with dendritic cells that then carry the information from those antigens or pathogens to naïve B and T cells, and “activate” them to be specific for those antigens or pathogens. Following their activation, naïve T and B lymphocytes clone themselves then migrate to the regional mesenteric lymph node. They enter the lymphatics, and from there the venous circulation and systemic blood supply, ultimately migrating back to a specific anatomical region of the GI tract.

The next step — chronic disease

When allergens and pathogens are prevented from being absorbed into the systemic circulation by healthy mucosal barrier mechanisms, there can be no systemic immunological response. Disrupted bowel barrier function, however, will lead to inappropriate increases in antigen and toxin loads and will disrupt detoxification mechanisms, thereby creating increased immune system and liver enzyme mobilization. Over time, this can lead to chronic pathology.

Impaired barrier function can also lead to diseases of the immune system. For instance, when bowel permeability increases, classic hypersensitivity to foods and components of normal gut flora can result. Bacterial endotoxins, cell wall polymers and dietary gluten may cause non-specific activation of pro-inflammatory pathways. Chronic low grade endotoxemia has been shown to contribute to the development of autoimmune disorders. Increased intestinal permeability may be either involved in the course of each disease, or a secondary effect of the hyperpermeability leading to immune activation and hepatic dysfunction, and creating a vicious cycle of disease promotion.

Measuring intestinal permeability

The measurement of increased intestinal permeability in animals requires urinary collection with a urinary catheter in place. This makes it more difficult to diagnose without hospitalization. Typically, in the measurement process, different-sized, non-digestible long chain sugars are orally administered and collected in the urine. The ratio of shorter to longer chain sugars defines whether the barrier has been breached. Thus, unless it is being specifically measured, the role of increased intestinal permeability often goes unrecognized.

An emerging methodology of food sensitivity and intolerance testing measures food ingredient-specific IgA and IgM in the patient’s saliva, and serves as a practical, non-invasive screening for increased intestinal permeability. Secretory (mucosal) IgA is lower with a disturbed intestinal barrier mechanism, and this test can help quantitatively measure food-related antibodies directed against IgA and IgM. Preliminary studies suggest this testing methodology yields highly accurate results.

The 4 R’s

Leaky gut syndrome can be treated and managed successfully with a four-part treatment program (“The 4Rs”) that uses diet, herbs and nutraceuticals. Many naturally-occurring substances can help repair the intestinal mucosal surface, or improve hepatic function when it is overwhelmed by an excessive total toxin load.

REMOVE pathogens, allergens and toxins. By lowering the “total load” (the body’s burden) of these troublesome substances, the immune system and liver do not need to work as hard in processing them. This makes more energy available for re-establishing healthy patterns. Removal can be done by elimination from the diet or environment, or with agents such as antimicrobial agents.

REPLACE digestive factors that are inadequate or absent. Inadequate pancreatic or intestinal enzyme production leaves digesta only partially broken down, thus altering the environment in the bowel and providing opportunity for pathology to develop. The beneficial bacteria that produce short chain fatty acids (SCFA) from soluble fiber in the bowel need a narrow range of temperatures and pH, as well as adequate substrate for their activity. When food is only partially digested, the intermediate breakdown products of digesta do not promote healthy microfloral ecology.

REPAIR the damaged intestinal mucosal barrier. The amino acid l-glutamine reduces bacterial translocation, and increases the protein synthesis of enterocytes, enabling them to increase their rate of self-repair. Lecithin, and the Omega-3 fatty acids commonly found in fish oil – EPA and DHA – are also integral to repairing intestinal mucosa damaged from disease, stress, toxins or diet.

Antioxidants reduce damage to intestinal mucosa. Zinc and vitamin B5 are involved in the mucosal repair process. Soluble fiber promotes SCFA production which provides nourishment for damaged colonocytes. Rice protein solids have been found to reduce intestinal secretions and improve re-absorption of water from colonic digesta.

REINOCULATE with probiotic cultures and accessory nutrients to create healthy bowel ecology. Endogenous and transient probiotic GI microbial flora are extremely important. Anaerobes are the most numerous bacteria in the bowel. These beneficial microorganisms compete with potential pathogens for nutrients and attachment sites to the mucosa, thereby inhibiting “bad” bacterial overgrowth.

In Bella’s case, a home-prepared diet made from hypoallergenic ingredients and implementation of the 4R program helped her regain a healthy weight within three months.