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) I n Fo c u s

Intestinal Permeability and


Its Role in Disease
By David Lescheid, PhD, ND

digested and absorbed to maintain


normal body functions (Figure). In
Maintaining integrity in the gastrointestinal (GI) tract
the healthy GI tract, with intact mu-
is of paramount importance in our overall health. The cous membranes, tolerance is the
commonly recognized functions of the GI tract (digestion, predominant immunological func-
tion. Therefore, we do not react to
secretion, absorption, and motility) can occur effectively the daily nutrients that we need to
only if there are intact epithelial membranes. These func- support our physiological func-
tions. If the GI tract barrier is com-
tions must occur properly to provide us with the nutrients
promised, there is a breakdown in
that we need to support our activities of daily living. tolerance, leading to increased reac-
tivity, chronic activation of immune
system cells, and production of cy-
tokines that can have localized and

T he mucous membranes of the


GI tract also provide com-
partmentalization, protecting the
gut-associated lymphatic system
(GALT) is part of an interdependent
mucosal immune system termed the
systemic effects.
Some of the more common diseases
associated with a breakdown in the
relatively fragile, homeodynamic mucosa-associated lymphatic system integrity of the GI tract include the
internal milieu from the relatively (MALT). Immunocompetent cells inflammatory bowel diseases3 and
harsh environment of the intestinal that develop in the GALT are trans- certain autoimmune diseases, such
lumen. Mucosal membranes include ported via the lymphatic system to as ankylosing spondylitis, IgA neph-
many different structures and cells the circulatory system to be carried ropathy and multiple sclerosis,4 type
with unique roles in maintaining to other mucous membranes, such as 1 diabetes mellitus,5 and autism.6
the physical, chemical, and immu- the respiratory and urogenital tracts, Other conditions associated with
nological barrier functions.1 to provide protection. This inter- a hyperpermeable GI tract include
Another major function of the GI dependence between all mucous congestive heart failure,7 chronic ve-
tract is immunity. The epithelial membranes in the body is important nous insufficiency and the develop-
cells of the GI tract provide the first because it means that by using bio- ment of leg ulcers,8 major depressive
line of defense, protecting us from regulatory medicines to restore in- disorder,9 chronic fatigue immune
the potentially dangerous or foreign tegrity in the GI tract, we can influ- deficiency syndrome,10 gallstones,11
substances brought into our body ence the overall immune system and and progression of human immuno-
via our food and drink. Furthermore, general health. deficiency virus (HIV) infection.12
most pathogenic microbes, including The immunological barrier func- The documented relationship be-
many medically important viruses,2 tion is a very dynamic and complex tween a “leaky gut” and so many
must cross a mucosal barrier to cause one, with roles not only in protec- important diseases, as described,
disease. It is estimated that up to tion from substances that are for- speaks to the importance of medical
80% of the immune system cells are eign and/or potentially dangerous interventions that can safely and ef-
)4 initiated in the GI tract or spend a but also in tolerance to commensal fectively promote healing in a time-
good portion of their life there. The microflora and the nutrients that are ly manner. This article will describe

Journal of Biomedical Therapy 2009 ) Vol. 3, No. 2


) I n Fo c u s

the scientific support for the use of integrity and that all 3 pillars of ho- toxins), Support (the organs of de-
antihomotoxic medicines in treat- motoxicology (i.e., organ regulation toxification and drainage), Stimulate
ing a hyperpermeable GI tract and and cellular activation, immuno- (elimination of toxins), and Sensitize
restoring optimal health. modulation, and detoxification) will (the patient for detoxification). Oth-
have to be used to provide complete er toxins that affect the permeability
Using homotoxicology to treat resolution. of the GI tract include pharmaceu-
a hyperpermeable GI tract In any disease, it is important to first tical drugs, such as proton pump
One of the inherent strengths in examine the broader picture and ask inhibitors16 and nonsteroidal anti-
homotoxicology is that it provides what external influences might be inflammatory drugs (e.g., cyclo­oxy­
a very well thought out, logical ap- contributing to the disease or act- genase [COX] 2 inhibitors).17,18 Zeel
proach to the progression of diseases ing as obstacles to cure the disease. has been shown to be as effective as
and of disease regression. The Dis- For example, we know that many COX-2 inhibitors in a clinical trial
ease Evolution Table (DET) outlines substances (e.g., gluten, certain food of patients with mild to moderate
a framework from which to position additives, heavy metals, and inhal- arthritis of the knee.19 There are
a disease in relation to its status of ants) affect the permeability of the numerous clinical trials demonstrat-
regulation and deregulation and to GI tract. Microbial infections and ing that topical Traumeel effective-
which germ layer of tissue has been aging also can increase permeability. ly manages pain in many different
affected. It also provides a relative Excessive, regular consumption of musculoskeletal disorders, including
guide as to the prognosis of the dis- alcohol13,14 and high fructose corn acute symptomatic treatment of ten-
ease and the phases that might oc- syrup15 are also associated with the dinopathy.20 These studies suggest
cur during healing. On the DET, a development of a leaky gut in sus- that antihomotoxic medicines can
leaky gut is classified on the vertical ceptible people. It is important to be used as anti-inflammatory agents
axis in the section on endodermal discontinue this external supply of that will not damage the GI tract.
tissue, just to the right of the regu- toxins as a first step towards reso- The permeability of the GI tract is
lation/compensation division in the lution. Discontinuing these toxins not only affected by physical toxins,
impregnation phase. It means that it supports the 4-S approach to detox- but also by lifestyle events or stres-
will take some time to restore gut ification: Stop (the external supply of sors on mental or emotional levels.

Blood
stream Blood flow to the liver

Lymph Figure. Intestinal mucosa. The mucosal


node barrier prevents harmful substances
(e.g., toxins, pathogenic bacteria, and in-
CRH and TRH receptor flammatory mediators) from entering
the body. At the same time, it serves as
a highly selective filter, ensuring the
absorption of useful substances (e.g.,
food particles) through tight junctions
and epithelial cells.
Abbreviations: CRH, corticotropin-re-
Tight
Probiotic bacteria junction Epithelial leasing hormone; NSAID, nonsteroidal
CRH
barrier anti-inflammatory drug; TRH, thyrotro-
NSAIDs Unstirred water Enterocyte
Food particles Alcohol pin-releasing hormone.
Bacteria Mucus layer

)5

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) I n Fo c u s

For example, it has been shown that output from the brain can play in
even a short period of sleep depriva- healing the leaky gut. Several ef-
tion in mice will cause a profound fective methods of modulating this
change in permeability of the GI pathway include acupuncture, bio-
tract and translocation of bacteria feedback, mindfulness meditation,
to normally sterile sites, such as the various forms of physical therapies,
mesenteric lymph nodes, spleen, and chiropractic techniques.28,29 Fur-
pancreas, and blood.21 Chronic in- thermore, there are a number of an-
somnia in humans is also associated tihomotoxic medications that have
with the production of proinflamma- been shown to be very effective in
tory cytokines and the reduction of modulating the psychosomatic in-
antioxidant systems and hormones fluences on disease states. These
that can lead to hyperpermeability include Nervoheel, for anxiousness
in the GI tract.22 Neurexan is an an- and irritability23,30; Neuro-Injeel/
tihomotoxic medicine that is useful Neuro-Heel, for deeper pathologies,
in treating insomnia and helping to particularly for someone who has
relax persons who are overstimu- never been well since a specific life
lated by the stressors of daily liv- event; and Tonico-Injeel/Tonico-
ing.23 Modulating stressors, such as Heel, for physical and mental ex-
insomnia, can be an important part haustion from overwork.23
of treating a leaky gut because it has Correcting any dysregulation in the
been shown in animal studies that brain is an important component
chronic psychological stress will of healing a leaky gut. This heal-
cause hyperpermeability in the GI ing can occur indirectly by modu-
tract and predispose the animals to lating shared signaling molecules,
hypersensitivity and illness.24,25 such as cytokines, between the or- Cross section of gut mucosa
We have known for years that there gans, as described previously. Al-
is a connection between the nervous, ternately, this restoration can occur
endocrine, and immune systems via directly because there is recent evi- 1. Organ regulation and
shared signaling molecules, recep- dence that physical structures previ- cellular activation
tors, and anatomical locations.26,27 ously thought to be found only in There are a number of different
This field of psychoneuroimmunol- the central nervous system are also antihomotoxic medicines that will
ogy has provided the scientific proof found in the GI tract.31 This is the support and regulate the organs of
that there is a gut-brain connection so-called brain-gut axis. It is sug- the GI tract. One of the key struc-
and that physiological or pathologi- gested that “cellular interactions tures contributing to the physical
cal changes in one of these organs previously thought to be unique to barrier function of the GI tract is
profoundly influence the func- the blood-brain barrier, also regulate the tight junction between the epi-
tion of the other organ. Recently, a gut epithelial permeability.”31 This thelial cells. These tight junctions
parasympathetic anti-inflammatory evidence provides further support ensure that most of the substances
pathway has been described; this to the potential of using medicines that are absorbed follow the intra-
pathway connects the cytokine sig- commonly considered to be nervous cellular pathway rather than the
nals in the GI tract with vagus nerve system specific as adjuncts to heal- paracellular pathway. By follow-
fibers, the brain, acetylcholine and ing the GI tract. ing the intracellular pathway, they
its receptors on macrophages, and Once the external factors contribut- are carefully processed by the in-
further changes in cytokine sig- ing to the development of a leaky tracellular enzymes and biochemi-
nals.28,29 This pathway, termed the gut, or interfering with self-reg- cal pathways of the epithelial cells
cholinergic anti-inflammatory path- ulation, have been identified and before they enter the lymphatic or
way, provides the evidence needed addressed, it is important to begin circulatory systems to be carried to
to support the role that modulat- treatments using the 3 pillars of ho- the rest of the body. Two important
)6 ing parasympathetic nervous system motoxicology. processes in GI epithelial cells are
the cytochrome P450 enzyme sys-

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) I n Fo c u s

tems,32,33 which are involved in the energy-dependent process can be and present them to naïve T cells.
phase I and phase II detoxification supported by the use of Coenzyme Depending on the nature of these
of substances; and the p-glycopro- compositum, an antihomotoxic substances, their dose, and the ex-
tein and cation/anion transporter medicine that is thought to generate tent of interaction, different types
systems,34,35 which act as phase III ATP via its influence on the intracel- of cytokines are synthesized and
transporters regulating the influx lular Krebs/tricarboxylic acid cycle. secreted. These cytokines influence
and efflux of certain drugs, metals, the direction of T-cell development
and toxins. The function of both of 2. Immunoregulation towards either T-helper cell type 1
these systems can be supported by If the tight-junctional complexes (Th1)-dominant (cell-mediated) im-
Mucosa compositum. Furthermore, become permeable, macromolecules, munity or Th2-dominant (humoral)
these intracellular processes are en- including substances in food and immunity. Other T cells, termed
ergy dependent and, therefore, the drink that have not been thoroughly Th3 and/or Treg cells, play a role
use of Coenzyme compositum is in- processed and microflora and their in ensuring that the immune system
dicated to help support the Krebs/ endotoxins, cross into the support- shift in either direction is moderated
tricarboxylic acid cycle generation ing aerolar connective tissue and in- and not too vigorous or persistent. A
of adenosine triphosphate (ATP). teract with the immune system cells detailed description of Th1/Th2/
The tight junctions are also com- located there. These interactions Th3/Treg immunity is beyond the
plex, dynamic structures that can be result in the synthesis and secretion scope of this article and is reviewed
influenced by many different types of inflammatory cytokines, such as in detail elsewhere.42-45
of stimuli,36 possibly including anti- interleukin (IL) 1b, tumor necrosis An enhanced understanding of the
homotoxic medicines. A breakdown factor (TNF) α, and interferon g. cytokines involved in the pathogen-
in the integrity of tight junctions These cytokines also directly affect esis of various diseases will assist in
has been associated with many dif- the tight-junctional architecture to the development and use of safe, ef-
ferent diseases.37 The tight-junc- further increase permeability.38,40 fective methods of modulating these
tional complex consists of a num- A positive feedback loop is set up, cytokines and recreating balance
ber of different proteins, including with increased intestinal perme- in the immune system to promote
zonulins, occludins, and claudins; a ability up-regulating the synthesis healing. Immunomodulation is an
number of different kinases; and a and secretion of proinflammatory important step in the healing of the
junctional adhesion protein, which cyto­kines that increase permeabil- leaky gut.
is a member of the immunoglobulin ity even further. Reversing a leaky Two of the most important cyto­
superfamily.38 The claudins and the gut requires repairing the physical kines directly contributing to in-
occludins form extracellular loops tight-junctional structure, as de- creased permeability in the GI tract
that span the gap between the cells. scribed previously, in addition to are IL-1b46 and TNF-α.38 There
The claudin proteins are water-filled modulating the inflammatory cy- are a number of specific targets for
pores that carefully select substances tokines that are further impairing these cytokines in mainstream medi-
that enter the paracellular pathway the healing process. According to a cine, including the monoclonal an-
based on charge and size. Zonulins number of animal and human obser- tibodies to TNF-α, infliximab and
act as tethering proteins linking the vational studies, it appears that the adalimumab; however, both of these
claudins to the intracellular matrix actual physical damage to the mu- medicines have a substantial num-
via their attachment to actin and my- cosal epithelial cell barrier occurs ber of potentially severe adverse ef-
osin. This structural arrangement of prior to the induction of excessive fects.47 A safer, effective way to mod-
the tight-junctional complex means proinflammatory cytokines.41 This ulate these cytokines is by using the
that changes in the intracellular ma- further strengthens the importance antihomotoxic medicine Trau­meel.
trix, via actin-myosin interactions, of structural and functional organ Using in vitro studies, the extent of
can affect the opening and closing support, as described previously, modulation of TNF-α and IL-1b
of the claudin pores and, therefore, as an initial strategy to treating the by Traumeel is significant, ranging
the integrity of the epithelial barrier. leaky gut. from 54% to 70%, respectively.48
The myosin heads have ATPase ac- Once substances have crossed the Echinacea compositum is an anti-
tivity and, therefore, hydrolyze ATP mucosal epithelial cell barriers, anti- homotoxic medicine that has been
to provide the energy to help them gen-presenting cells (e.g., dendritic shown to effectively prevent post-
)7
move along the actin strands.39 This cells) collect them, process them, operative infections.49 There is re-

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) I n Fo c u s

cent evidence that the alkylamides of the mucous layer are trefoil fac- based on their charge and size. For
from extracts of the root of Echi- tor peptides (TFFs) and mucin.54 this careful, selective process to oc-
nacea species modulate TNF-α, via Both of these components are syn- cur optimally, the mucins need to
the endogenous cannabinoid recep- thesized and secreted by the goblet be relatively free of toxins. Further-
tors.50,51 The N-alkylamides of Echi- cells interspersed throughout the more, regulating proinflammatory
nacea purpurea work synergistically mucous membrane. They migrate cytokines also helps mucins to as-
to not only decrease the expression onto the luminal side of the epithe- semble and function appropriately.61
of TNF-α but also to increase the lial cells to provide an extra viscous It can be postulated that using Lym-
expression of IL-10,52 a cytokine layer of protection and selective phomyosot and Traumeel might
known for its immunosuppressive filtration.55,56 The synthesis and re- help to keep the mucin structures
effects on Th1-dominant diseases lease of TFFs is diurnal, with a peak clear and able to perform their func-
such as Crohn’s disease. time during the nocturnal hours. tions optimally; this is an important
Because of the ability of Echinacea This protective rhythm is disrupted contributing factor to healing a hy-
extracts to shift the immune system by aging, a Helicobacter pylori infec- perpermeable GI tract.
towards Th2-dominant immunity, it tion, sleep deprivation,57 and celiac Many of the immune system cells of
is important to use them with cau- disease.58 Furthermore, there is evi- the GALT are present in the loose
tion and only in conditions in which dence that modulating proinflam- areolar connective tissue just below
they are unlikely to aggravate signs matory cytokines, such as TNF-α, the epithelial cells.1 For these im-
and symptoms. For example, ulcer- also helps maintain optimal levels of mune cells to work optimally, there
ative colitis is considered a Th2- TFFs,59 suggesting that this might must be a relatively clear pathway for
dominant disease53 and, therefore, be another mechanism by which antigens to be able to be received by
any medical intervention (e.g., with Traumeel can act to help in the res- them. Furthermore, these immune
Echinacea extracts) that promotes toration of gut integrity. system cells must have a relatively
further development of Th2 cells high degree of mobility to move
might cause an aggravation of symp- 3. Detoxification to where they are needed to mount
toms. Furthermore, persons who are Once the organs of the GI tract have an appropriate immune response. In
sensitive to plants in the Asteraceae been supported and the proinflam- my opinion, using drainage prepara-
family also might be sensitive to matory cytokines have been modu- tions, such as Lymphomyosot, may
Echinacea extracts. Finally, because lated to the point at which they can help keep this loose areolar connec-
Echinacea species extracts, in partic- self-regulate, it is important to en- tive tissue relatively free of exotoxins
ular the aerial parts, have immuno- sure that all remaining endotoxins and endotoxins; this is an important
stimulatory activity, it is suggested and exotoxins are detoxified and part of ensuring that an appropriate
that they are not administered in drained. Clearing toxins also helps immune response occurs.
full concentrations to persons with to activate physiological systems It is important to recognize that
autoimmune conditions. A ho- that protect the GI tract from further there is a closely regulated, inter-
meopathic concentration of D4 damage. In addition to the TFFs, an- dependent relationship between the
(1:10,000) is considered safe for other important component of the GI tract and the liver. The stomach,
oral use and, therefore, the use of mucous layer is mucin. Mucins are intestine, spleen, and pancreas drain
Echinacea compositum drinking large extracellular proteins that are to the liver via the hepatic portal
ampoules is safe in autoimmune and heavily glycosylated with a bottle system. Therefore, many of the tox-
proliferative conditions. brush-like structure. The mucins ins from a leaky gut will end up in
Even before substances in the GI play a number of roles, including the liver, where they need to be pro-
tract lumen reach the epithelial control of cell growth, signal trans- cessed. Furthermore, if the detoxifi-
cells or tight-junctional complexes, duction from the lumen to the intra- cation mechanisms in the liver are
they must diffuse through a mucous cellular structures, adhesion of com- not functioning adequately, excess
layer. The mucous layer is not sim- mensal and potentially pathogenic or insufficiently processed toxins are
ply a static physical structure. It is microbes, and protection.60 Their recycled back into the duodenum of
highly dynamic, with a meshwork protective function is due in part to the GI tract via the bile duct. Using
of many different interdependent the ability of the glycoproteins to Nux vomica-Homaccord or Hepar
)8 proteins and carbohydrates. Two of act as a molecular sieve, carefully compositum to support liver de-
the best-characterized components regulating diffusion of substances toxification systems and Coenzyme

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) I n Fo c u s

compositum to support the energy many diseases. Management begins could be interfering with restoration
demands of these systems is thus by discontinuing the intake of po- of mucosal integrity. Finally, it is im-
important. The addition of Berb- tentially damaging toxins or lifestyle portant to remove toxins and to ac-
eris-Homaccord reduces the toxin choices and replacing or repairing tivate the organs, so that they main-
burden even further by support- them with antihomotoxic medicines tain optimal detoxification pathways
ing the detoxification and drainage that will not cause any further dam- even after therapy has been discon-
functions of the kidneys and liver. age. It is important to support the tinued.
Animal studies14,62 have shown that ability of the various organs to per- The science and art of homotoxicol-
excess alcohol consumption causes form their physiological functions ogy provides us with a scientifically
direct damage to hepatocytes and (using Mucosa compositum, Nux supported, logical framework to
leads to the development of a leaky vomica-Homaccord, and Coenzyme heal a hyperpermeable GI tract and,
gut. The increased toxin load, subse- compositum) and to immunomodu- therefore, support maximal health
quent to this increased GI tract per- late cyto­kines, such as IL-1b and in our patients. One of the addi-
meability, further contributes to liv- TNF-α (using Traumeel and Echi- tional strengths of antihomotoxic
er damage, stressing the importance nacea compositum). This will halt medicine is that the medications can
of addressing the health of the liver the positive feedback loop of in- be used synergistically with other
and GI tract simultaneously. creased permeability, production of natural health products to support
excess proinflammatory cytokines, timely and effective healing. Other
Conclusions and further permeability. It is also natural health products shown to be
Because of the paramount impor- important to recognize that there useful in healing the leaky gut in-
tance of the mucosa in systemic is a definitive gut-brain connection clude probiotics,62-64 quercetin,65-68
immune responses and the connec- and, therefore, it is essential to ad- L-glutamine,69-71 zinc,72-74 zinc car-
tivity between all of the mucosal dress any mental and/or emotional nosine,75 vitamin A,76 vitamin D,77,78
barriers in the body, repairing a disturbances (using Neurexan, Neu- melatonin,79 curcumin,80-83 and lico-
leaky gut can be an important ac- ro-Heel/Neuro-Injeel, Nervoheel, rice extracts.84|
cess point in the management of or Tonico-Heel/Tonico-Injeel) that

Hans-Heinrich Reckeweg Award 2010


Join in – have your experience rewarded Both prizes are awarded for research carried out in a
Heel annually honors outstanding scientific research in laboratory or registered practice. All results must be
the field of a unique homeotherapeutic system (homo- new, convincing and previously unpublished, and re-
toxicology) with the Hans-Heinrich Reckeweg Award. search should not have involved animal testing.
The deadline for submissions is May 31, 2010.
The main award (€ 10,000)
is presented for scientific work of fundamental theo- For more information contact:
retical and/or practical significance in antihomotoxic Biologische Heilmittel Heel GmbH,
medicine in the fields of human and veterinary medi- Department of Research,
cine. 76532 Baden-Baden, Germany
Phone +49 7221 501-227,
The incentive award (€ 5,000) Fax +49 7221 501-660, info@heel.de,
is presented for promising results arising from clinical, www.heel.com
case-based or fundamental research in antihomotoxic
medicine in the fields of human and veterinary medi-
cine. The prize money is intended to fund further re-
)9
search.

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) I n Fo c u s

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