Increased Intestinal Permeability
Syndrome
By Casey
Adams, Ph.D.
For
years naturopaths and herbalists described a digestive disorder termed “leaky
gut syndrome.” This was largely dismissed by the medical establishment as
anecdotal and non-existent. In recent years, however, research on intestinal
drug absorption by the pharmaceutical industry has confirmed that the lining of
the small intestine is subject to alteration, dramatically affecting absorption
and permeability. As this research has progressed it has become apparent that
not only can drug absorption be affected, but nutrient absorption can be
significantly reduced due to permeability alteration. Even worse, increased
intestinal permeability syndrome (IIPS) may well be implicated in many allergic
and arthritic conditions.
Increased
permeability of the small intestinal tract has been the focus of drug research
looking to give pharmaceuticals greater access to the blood stream. However, as
naturopaths have warned over the years, increased permeability can also allow
larger macromolecules—larger peptides, toxins and even invading micro-organisms—into
the bloodstream. Once these foreign macromolecules arrive in the bloodstream,
the immune system may activate cytokines and lymphocytes along with the rest of
the inflammatory immune response cascade as a defense measure. Worse, the
invasion of micro-organisms through the intestinal wall can result in bacterial
translocation throughout the body.(1,2) Illustrating this mechanism, Blastocystis hominis, a
distinctly intestinal pathogen, has been found in synovial membranes of
infectious arthritic patients.(3)
Holistic
doctors have attributed this influx of macromolecules into the bloodstream as a
major cause for the increasing occurrence of food allergies in western society.
Typically, intestinal barriers let only smaller molecules access to the liver and
bloodstream—usually beneficial nutrients. Should larger, undigested food
molecules enter the bloodstream—even if from a food consumed for decades—the
body’s immune system will not recognize them. This can lead to IgA and/or IgE
responses, with associated histamine conversion causing skin and/or sinus
inflammatory responses. IIPS can thus result in the double-edged eventuality
that a food, formerly a source of nutrition, can suddenly be identified by the
immune system as toxic, resulting not only in allergic response, but also in
nutritional deficiencies. Research is finally confirming these
previously-suspected mechanisms.(4,5)
Inflammatory
responses resulting from IIPS have increasingly been attributed to cases of
sinusitis, allergies, psoriasis, asthma, arthritis and more by holistic doctors
aware of these mechanisms. Overgrowth of Candida
albicans, a typical fungal inhabitant of the digestive system at minimal
numbers, has also been attributed to IIPS. It has been proposed that systemic Candida infections have a route of
translocation via IIPS. Research further confirms a correlation between
increased permeability and liver damage.(6)
The IIPS Mechanism
The
mechanism of increased intestinal permeability is complicated. There are now
seven identified means of intestinal absorption in a healthy system: passive transcellular; active transport; facilitated diffusion;
passive paracellular; efflux transport; first-pass
absorption and receptor-mediated transport.(8)
The
intestinal brush barrier, a complex
mucosal layer of enzymes, probiotics and ionic fluid, forms a protective
surface medium over the intestinal epithelium. It also provides an active
nutrient transport mechanism. This mucosal layer is stabilized by the grooves
of the intestinal microvilli. It contains
glycoproteins and other ionic transporters which attach to nutrient molecules,
carrying them across intestinal membranes. Meanwhile the transport medium
requires a delicately pH-balanced mix of ionic chemistry able to facilitate
this transport of amino acids, minerals, vitamins, glucose and fatty acids. The
mucosal layer is policed by billions of probiotic colonies which help process
incoming food molecules, excrete various nutrients, and control pathogens. (In
the proper mucosal environment, probiotics will produce several B vitamins and
potent antibiotics.)(9)
The
epithelium of the intestinal tract functions as a triple-filter barrier that
screens for molecule size, ionic nature and nutrition quality. Much of this is
performed via three mechanisms existing between the intestinal microvilli: tight junctions, adherens
junctions and desmosomes. The tight functions form a bilayer interface between cells, controlling permeability. Desmosomes are points of interface between the tight
junctions, and adherens junctions keep the cell
membranes adhesive enough to stabilize the junctions. These junction mechanisms
together regulate permeability at the intestinal wall.
The
mucosal brush barrier and the microvilli junctions
together form the boundary between intestinal contents and our bloodstream.
Should the mucosal layer chemistry become altered, its protective and ionic
transport mechanisms will become weakened, allowing toxic or larger molecules
to be presented to the microvilli junctions. This contact
can irritate the microvilli, causing a subsequent
inflammatory response. Such a response will weaken the microvilli
junctions, allowing the larger molecules immediate access to the bloodstream.
Alteration
of the intestinal mucosal layer and the subsequent weakening of the microvilli junctions can be caused by a number of factors.
The conclusion of researchers and many holistic doctors is that alcohol/ethanol
is one of the most irritating substances to the mucosal lining and
junctions.(6,10) In addition, many pharmaceutical drugs, notably NSAIDs, have been identified as damaging to the mucosal
chemistry and junction strength. Foods with high arachadonic fatty acid
capability (such as trans-fats, animal meats, etc.); low-fiber, high-glucose
foods; and high nitrite-forming foods have been suspected for their ability to
compromise the intestinal lining. Toxic substances such as plasticides,
pesticides, herbicides and food dyes are also suspected. In general, substances
which increase PGE-2 response are suspected to negatively impact permeability.(11) In addition, the overuse of antibiotics can cause a
die-off of the all-important resident probiotic colonies. With intestinal
probiotic counts decreased, pathogenic bacteria and yeasts can outgrow
probiotic colonies. This pathogenic bacteria growth invades the brush barrier,
introducing an influx of endo-toxins (the waste
matter of these micro-organisms) to the bloodstream together with some of the
micro-organisms themselves.(4) Lack of hydration and
stress are also suspected as contributing factors to IIPS.
Fortunately,
most of the epithelial cells of the small intestine are replaced within about a
week, and proper mucosal chemistry can gradually be re-established with
appropriate dietary and lifestyle changes. A balanced natural and fiber-rich
diet; a decrease in toxins and unnecessary pharmaceuticals; together with
probiotics and detoxification measures can help maintain a healthy,
appropriately-permeable small intestine.
Casey Adams, D.Sc., A.M.P., N.P. holds a doctor of integrative health
sciences and is board certified as an alternative medical practitioner. With
many years of service in the organic, natural food, nutraceutical and herbal
industries, he currently consults and gives workshops at the
References (1) Baik HW. Nutritional therapy in gastrointestinal disease. Korean J Gastroenterol. 2004 Jun;43(6):331-40. (2) Yasuda T, Takeyama Y, Ueda T, Shinzeki M, Sawa H, Nakajima T, Kuroda Y. Breakdown of Intestinal Mucosa Via Accelerated Apoptosis Increases Intestinal Permeability in Experimental Severe Acute Pancreatitis. J Surg Res. 2006 Apr 4. (3) Kruger K, Kamilli I, Schattenkirchner M. Blastocystis hominis as a rare arthritogenic pathogen. Z Rheumatol. 1994 Mar-Apr;53(2):83-5. (4) Laitinen K, Isolauri E. Management of food allergy: vitamins, fatty acids or probiotics? Eur J Gastroenterol Hepatol. 2005 Dec;17(12):1305-11.
(5) Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005 Sep;2(9):416-22. (6) Bode C, Bode JC. Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):575-92. (8) Balimane P, Yong-Haen H, Chong S. Current Industrial Practices of Assessing Permeability and P-Glycoprotein Interaction. J AAPS 2006; 8(1). (9) DeWitt RC, Kudsk KA. The gut's role in metabolism, mucosal barrier function, and gut immunology. Infect Dis Clin North Am. 1999 Jun;13(2):465-81. (10) Ferrier L, Berard F, Debrauwer L, Chabo C, Langella P, Bueno L, Fioramonti J. Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents. Am J Pathol. 2006 Apr;168(4):1148-54. 11. Martin-Venegas R, Roig-Perez S, Ferrer R, Moreno ©
copyright Realnatural Health