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Herbal Antimicrobials for Intestinal Infections
by Myron Lezak, M.D.
Increases in international travel, immigration,
animal transport, improper food handling, and drug-resistant
bugs have led to an explosion in infectious disease of all types,
as well as a need for new, safe antimicrobials. The gastrointesti-
nal tract is called upon to function as an effective physical and
immune barrier; and, because the intestinal tract can become a
breeding ground for microbes, intestinal health is of critical
importance. Imbalanced intestinal flora (dysbiosis) and intesti-
nal infections not only cause localized problems, but can have
systemic manifestations previously thought unrelated to intesti-
nal health. With the involvement of gut origin (enteric) microbes
in increasing numbers of disease processes, it becomes impera-
tive to recognize, treat, and restore health to the intestinal tract.
Herbs such as thyme, oregano, barberry, wormwood, garlic, and
others appear efficacious as antimicrobial agents against the
plethora of microbes threatening intestinal health; in addition,
they benefit multiple organs and organ systems—a basic tenet of
herbal therapy.
People need safe and effective substances to combat the rise in
infectious diseases now evident in all parts of the world. Increases
in mass population movements, international travel, and trans-
portation of animals and animal products have helped carry dis-
eases into areas where they’ve never been before. Furthermore,
diseases can now be transported from one continent to another in
a matter of hours, and infections commonly associated with
“developing countries” are on the rise in America and Europe.1For
instance, the incidence of intestinal parasitic infections has risen
since the 1970s, and researchers conclude that intestinal para-
sitism should not be overlooked as a cause of gastrointestinal (GI)
illness in the United States.2,3Even the incidence of disease due to
yeast (i.e., fungi) pathogens has increased.4 Furthermore, food-
borne pathogens such as Salmonellaand Eschericia colicontinue
to be a threat due to changes in food production, handling, and
processing, as well as the international food trade.1,5
With the arsenal of drugs available to treat infectious disease
being progressively depleted as a result of microbial resistance,
the need for alternative treatments is greater than ever.3,6
Fortunately, nature offers effective therapies that have been used for
centuries in traditional medical practices to treat illness related to
enteric, pathogenic organisms.7-9 Advances in the isolation, extrac-
tion, and verification of active compounds from various herbs
allows for the production of safe, potent formulas that enhance the
body’s own defenses and have direct antimicrobial action.
Intestinal Ecology and the Link to Systemic Disease
To appreciate the need for safe antimicrobial agents with action in
the GI tract, it is critical to understand the relationship between GI
health and systemic disease. The gastrointestinal tract performs
critical digestive, immunologic, and barrier functions.10 Both non-
immunologic processes (i.e., gastric secretions, proteolysis, peri-
stalsis, mucous production, membrane composition) and the local
mucosal immune system (gut associated lymphoid tissue or
GALT) work in concert to form an effective barrier to the attach-
ment and penetration of microorganisms, antigens, and toxins that
are present in the gut environment at any given time.10-13
In recent years, the deleterious consequences of imbalanced intesti-
nal flora (dysbiosis), intestinal infection, and mucosal barrier dys-
function have become clear. Indeed, remote infection with an enteric
organism can occur in other organs and systems (e.g., typhoid,
paratyphoid, listeriosis, and hepatitis A and E), but reactionary
mechanisms associated with their very presence in the intestines can
have a systemic impact as well, leading to autoimmune pathology
and other chronic diseases.11,14-17 For instance, reactive and septic
arthritis have long been associated with enteric bacterial infections
including Salmonella.17 More recently, they have been associated
with a variety of GI parasites and Candidainfection.16,17
Published research has implicated intestinal dysbiosis and infec-
tion as the initiating step in a wide range of GI and systemic con-
ditions including: pancreatic disease, irritable bowel syndrome,
autoimmune arthropathies such as ankylosing spondylitis, psoria-
sis, eczema, cystic acne, chronic fatigue, uveitis, breast cancer, and
chronic heart disease.11,18-23 According to Dr. Leo Galland, et al.,
“Intestinal dysbiosis should be considered as a mechanism pro-
moting disease in all patients with chronic gastrointestinal, inflam-
matory or autoimmune disorders, food allergy and intolerance,
breast and colon cancer, and unexplained fatigue, malnutrition, or
neuropsychiatric symptoms.”23
Researchers postulate that interrelated mechanisms involved in the
systemic manifestations of a dysbiotic or infected gut include
inflammation, superantigens, molecular mimicry, and transloca-
tion, as discussed below.
Inflammation
The inflammatory response initiated by enteric microorganisms is
recognized as a contributing factor to intestinal tissue destruction
and mucosal barrier dysfunction.24,25 Stimulatory molecules that
initiate mucosal immunologic and inflammatory events include
microbial cell wall fragments (e.g., peptidoglycans, lipopolysac-
charides) and toxic microbial byproducts (e.g., exotoxins, endo-
toxins) produced by the array of microbes present in the GI tract
at any given time.10,24These molecules stimulate the inflammatory
process and can alter the balance of cellular mediators like
prostanoids, cytokines, nitric oxide, leukotrienes, TNF-alpha, and
interleukin 1 and 6, resulting in both local and systemic reactions.
Overstimulation by microbial molecules results in increased cir-
culating levels of these mediators, which are capable of tissue
destruction.10,24,26 For instance, evidence increasingly suggests that
tissue damage associated with irritable bowel disease might be
caused by a non-specific hyper-responsive inflammation, and
increased levels of these inflammatory molecules in circulation
may even contribute to the progression of atherosclerosis.27-29
Often, attenuation of destructive inflammatory events occurs with
resolution of infection.24,30
Microbial Superantigens
Superantigens are thought to be one of the most powerful micro-
bial stimulants that induce inflammatory and autoimmune reac-
tions.31-35 These protein structures (e.g., enterotoxins) have the
unique ability to nonspecifically activate large numbers of host T
cells, inducing the copious production of cytokines—the factor
largely responsible for all or part of their toxicity.31 They play a
role in toxic shock syndrome and mucocutaneous lymph node
syndrome, and are proposed to play a role in other systemic dis-
eases.32 Superantigens have also been implicated in autoimmune
disorders including rheumatoid arthritis, connective tissue dis-
ease, multiple sclerosis, and psoriasis.32,33The effects of superanti-
gens can be both acute and chronic; their role in pathogenesis is
based on their unproductive, destructive stimulation of the
immune system, including the activation of autoreactive T cells.34,35
Molecular Mimicry
The term molecular mimicry describes an occurrence between
pathogen and host in which the appropriate immune response
against an organism (often of enteric origin) results in an inappro-
priate autoimmune reaction. This reaction is caused by the simi-
larity between microbial antigens (proteins) and host cellular pro-
teins.36As a result, the immune system’s tolerance to self proteins
breaks down, and the pathogen-specific immune response cross-
reacts with host structures to cause tissue damage or disease.17
Therefore, molecular mimicry is thought to be a mechanism in
infectious disease-induced self-reactivity.37 For instance, Yersinia
enterocoliticahas been implicated as a contributing factor in the
development of thyroid autoimmunity (Graves’disease) due to its
crossreactivity with the thyroid stimulating hormone (thyrotropin)
receptor.38
Translocation
When mucosal barrier function is compromised, the opportunity
for microbes, toxins, and antigens to exit the intestines and enter
the blood, lymph, or visceral organs (translocation) increases.
Although translocation occurs randomly in healthy individuals,
factors that promote increased rates of translocation include
intestinal dysbiosis or infection, hyperimmune function, absence
of bile in the intestines, injury to the gut mucosa, inflammation,
and possibly portal hypertension.12,39-42 In an animal study of post-
antibiotic shifts in the intestinal environment, disturbance of
intestinal microflora appeared to be a greater promoting factor in
translocation than inflammatory activity.41,43 Research indicates
that bacteria, fungi, parasites, and viruses can translocate by sim-
ilar mechanisms from the intestinal tract.44 Once in circulation,
these materials have the ability to produce disease on various lev-
els (e.g., widespread infection, immune system activation).44
These data indicate the following scenario: when the intestinal
flora is imbalanced or pathogenic organisms are present, a cascade
of reactionary events occur that can affect the body on a local and
systemic level through alterations in cell signaling or remote
infection. These reactionary and interrelated events include
inflammation and immune hyperresponsivity, antigen reactivity,
and translocation. Moreover, they are all capable of inducing or
exacerbating intestinal tissue damage, further aggravating these
processes by increasing the systemic load of pathogenic, anti-
genic, immunologic, or inflammatory molecules.
Allopathic Treatment for Infection
There exists a vast array of prescription antimicrobial medications
to treat all forms of infection. Although generally effective for
managing acute infections, they not only can produce negative
side effects (e.g., superinfections, GI irritation, renal and hepatic
toxcity, anemia, etc.), but there is also an increasing resistance to
them.6,45 With the rise in new and old infectious diseases, and the
mobility of microbes across the planet, mainstream medicine is
becoming more receptive to the use of plant antimicrobials, which
appear to be effective, even against drug-resistant microbes.46
Combining Herbs for Effectiveness
For millennia, folk and ancient systems of medicine have used
particular combinations and ratios of herbs to achieve the safest,
most beneficial effect possible. Strategies for mixing plants were,
and still are, tightly linked to the perceived cause of illness as orig-
inating in an unhealthy relationship between an individual, their
predetermined nature (i.e., genetic make-up), and their immediate
environment that results in physical and/or mental imbalance.
Herbal formulas associated with traditional therapies generally
seek to restore balance within and between organ systems respon-
sible for the symptoms.7,47-51
According to traditional Chinese medicine (TCM), successful herbal
therapy means maximum benefits with minimal side effects.51 To
accomplish this, it is imperative to always distinguish the manifesta-
tion of the disorder from the root cause of a person’s complaints.
Both cause and effect are addressed by the herbal combination.
Because antimicrobial herbs need to be supplied at levels that can
sometimes cause digestive upset, TCM guidelines of combining
herbs are particularly useful in this model. To increase formula
tolerance and efficacy, the chief or central herb(s) target the infec-
tion, while additional herbs modify the action of the chief herb
and support other pathways known to be involved in the physical
process of restoring and maintaining balance in the GI tract. This traditional concept opposes Western herbology—supplying a sin-
gle potent herb—which may cause side effects when used at high
dosages. The TCM model of potency, balance, and efficacy com-
bines antimicrobial herbs, allowing for better concentration of
activity, while delivering additional benefits to the GI tract (i.e.,
digestive, purgative, secretory).7,51,52
Antimicrobial Compounds from Plants
Substances synthesized by plants (phytochemicals) produce odors,
pigments, and flavors, serving as plant defense mechanisms
against microorgansims, insects, and herbivores. Various plant
families including the mint, buttercup, ginger, lily, and rose yield
potent compounds or metabolites, and have been used both empir-
ically and clinically in humans for their antimicrobial activity, as
well as for their beneficial effects on digestive secretions, peristal-
sis, and inflammation.9,47-50Recent studies have validated empirical
observations, isolated active metabolites, and demonstrated their
toxicity to microbes both in vitro and in vivo.8,9,47-63
Phenols
Plants have the ability to synthesize a vast array of aromatic
substances, most of which are phenols—a group of bioactive
phytochemicals classified according to their chemical struc-
ture. Plants in this group include those belonging to the
Lamiaceaor mint family, such as red thyme (Thymus vulgaris),
oregano (Origanum vulgare), sage (Salvia officinale), and
lemon balm (Melissa officinalis). The aromatic Lamiacea
family is one of the most popular worldwide for use as carmi-
natives (to expel gas) and digestive aids, as well as for elimi-
nating unwanted microbes.8,49 In addition to cleansing the GI
tract, they also have an affinity for the respiratory tract and, as
such, their oils have been traditionally inhaled to ward off
pathogens.47,53 New technology has allowed for the combining
of essential oils with dry plant extracts, heretofore not available
in supplement form.
Red Thyme Oil(Thymus vulgaris)
The primary active in red thyme is thymol, whose action is
focused on the upper respiratory and gastrointestinal tracts.
Thyme extracts cause beneficial increases in mucous secretion of
the bronchii, and have a tradition of use in bronchitis, sore throat,
and whooping cough.9When compared with several antibacterials,
thyme extract also had a significant inhibitory effect on
Helicobacter pylori.54 Not only did it reduce the growth of H.
pylori, it made it more susceptible to stomach acid.54 In addition,
volatile components of thyme showed a great range of inhibition
against a variety of bacteria and fungi including E. coli and
Candida lypolytica, as well as important food-borne
pathogens.53,55,56Formulas containing red thyme oil should be stan-
dardized to thymol for maximum efficacy.
Oregano(Origanum vulgare)
Like red thyme, the primary active in oregano is thymol. In sever-
al studies, oregano has exhibited high levels of antimicrobial
activity against a wide range of Gram-positive and Gram-negative
bacteria, parasites, and fungi.55,57-59 Oregano has been traditionally
consumed in teas to treat stomach and gallbladder disorders, diar-
rhea, coughs, and asthma.9,47
Sage(Salvia officinalis)
Phenolic glycosides found in sage are potent antioxidants that sup-
port the health of mucosal surfaces; not surprisingly, sage was
often used in native cultures to prevent drying of the mucosa.60,61
According to the German Commission E, sage is antibacterial,
fungistatic, virostatic, astringent, and secretion-promoting.62 Sage
is indicated for use in digestive complaints, flatulence, inflamma-
tion of the intestines, and diarrhea.50,63
Lemon Balm (Melissa officinalis)
Lemon balm supplies flavonoids—metabolized in the body to
phenols—which support the action of the immune system.
Phenolic tannins found in lemon balm display potent antiviral
activity; for example, among other mechanisms, they neutralize
viruses on contact by attaching to them and preventing their union
with cell receptors.47,63
According to TCM, a combination of these aromatic, phenolic
compounds has the potential to assist digestion while harmonizing
healthy gut and respiratory environments.7,8,41 Because the aromat-
ic mint family has an affinity for the respiratory tract, the individ-
ual with gut problems who is susceptible to lung infections, or
those with chronic lung conditions that may be secondary to gut
infection, would find a combination of these herbs especially use-
ful. The relationship between the GI tract and lung conditions is
well recognized in traditional medical systems as well as Western
medicine (e.g., bacterial translocation to the lungs).7,45,51
Alkaloids
Alkaloids—heterocyclic nitrogen compounds—deliver a bitter
flavor, and for this reason, plants high in alkaloids are often
referred to as bitter herbs. Diterpenoid alkaloids are commonly
isolated from the Ranunculaceae, or buttercup, family and are
strongly microbiocidal.8 Berberine is a key representative of the
alkaloid group, and is present in medicinal plants such as coptis
(Coptis chinesis) and barberry (Berberis aristata).8,49 For nearly
3,000 years, extracts and decoctions of these plants have been
used in Ayurvedic and Chinese medicine.
Berberine
Berberine has been shown to have significant activity against bac-
teria, fungi, parasites, worms, and viruses.64 It not only exhibits a
broad spectrum of antibiotic activity, but it also inhibits toxin for-
mation as well as antagonizes formed toxins at the site of target
tissues.8,65,66 In one study, coptis showed an inhibitory effect on a
variety of toxigenic fungi, not only inhibiting its growth but
inhibiting its toxin production as well.67
Berberine sulfate was studied in 165 patients with infectious diar-
rhea due to enterotoxigenic E. coli and Vibrio cholerae.68 At a
dosage of 400 mg, the E. coli grouphad a significant reduction in
stool volume during three consecutive 8-hour periods after admin-
istration as compared to controls; 42% stopped having diarrhea
within 24 hours. Stool volume in the V. choleraegroup signifi-
cantly decreased in the second 8-hour period after administration.
These results indicate that berberine sulfate is a safe and effective
agent against E.coli diarrhea, and to a lesser degree, in patients
with severe cholera. In vitro experiments on the effects of berber-
ine on the growth and structure of parasites indicate that growth inhibition is dose dependent, inducing morphological changes
(e.g., clumping of chromatids, formation of autophagic vacuoles,
etc.) in common human parasites.69Furthermore, berberine proved
more effective than prescription antimicrobials in clearing patients
of Plasmodium falciparum(malaria), and when combined with
pyrimethamine (an antiparasitic drug) delivered the best results in
drug-resistant strains.46
Coptis Decoction
TCM practitioners familiar with the application of bitter plants
such as coptis, skullcap, phellodendron, and rhubarb, and their bit-
ter principles such as berberine, suggest that these plants be tem-
pered with additional herbs like ginger and licorice, which are
added to complement the bitter herbs and stabilize stomach and
intestinal function. A decoction of these plants not only provides
additional antibiotic activity and antioxidants, it improves the uti-
lization of, and tolerance to, berberine through its protective
effects on the lining of the stomach and intestines, thus comple-
menting any formula containing high levels of berberine.7,51
Other Antimicrobial Herbs
In addition to phenols and alkaloids, foods and herbs commonly
consumed in Asia and the Mediterranean including garlic, ginger,
sour plum, and wormwood have strong digestive, microbicidal,
and cleansing activity.
Garlic(Allium sativum)
The use of garlic to fight pathogens has a long and varied history.
Its use against amoebic dysentery, cholera, and other infectious
intestinal diseases is repeatedly discussed in the scientific litera-
ture.47,50,60 In fact, enterotoxic E. coli strains and other pathogenic
intestinal bacteria, which are responsible for diarrhea in humans,
are more easily inhibited by garlic than microbes that are part of
the normal gut flora.70 Garlic also has significant activity against
pathogenic fungi and parasites, and has proven to be a potent
inhibitor of two common, opportunistic human gastrointestinal
pathogens (Klebsiella and C. albicans).70,71 Allicin, a primary
active isolated from garlic, along with its metabolites (e.g.,
ajoene) are responsible for its antimicrobial activity.72
Ginger(Zingiber officinale)
Recently, the number of Anisakis (parasite) infections in the
United States has markedly increased due to the popularity of eat-
ing Japanese foods like raw-fish dishes.73 Anisakis is found in
many kinds of fish including mackerel, pollack, cuttlefish, hal-
ibut, tuna, flatfish, and codfish. Ginger has a potent lethal effect
on Anisakis larvae—eliminating its viability and infectivity—sub-
stantiating the rationale for its traditional consumption with raw-
fish dishes.73 Furthermore, ginger’s inhibitory effect on both
Gram-positive and Gram-negative bacteria has been validated
through in vitro experimentation.74,75 In the digestive arena, ginger
has anti-ulcer effects, enhances the secretion of bile, and promotes
gastrointestinal motility.76Anti-inflammatory properties of ginger
may also be beneficial in reducing the load of inflammatory mol-
ecules associated with intestinal infection.47,50 Components of gin-
ger, such as gingerol and shogaol, have been identified as active
principles, demonstrating the importance of standardization.73,76
Sour Plum(Prunus mume)
In a search for less toxic anthelmintics (deworming agents), the
effects of sour plum have been studied extensively on Clonorchis
sinensis—larvae found in raw or undercooked fish. Its suppression
of egg laying capacity, as well as the killing of worms, was shown
to be extensive.77 In TCM, sour plum is used to treat diarrhea and
dysentary, as well as expel hookworms and roundworms.7,47 The
herb also stimulates purging of parasites from the gallbladder, bile
duct, and intestines.48 In addition, decoctions of sour plum have
displayed in vitro inhibitory effects against various strains of food-
borne pathogens and other common bacteria and fungi.7
Wormwood(Artemisia annua)
Wormwood has been used for the treatment of fevers in China for
over 1,500 years; traditionally it was recognized as a treatment for
worms—consequently the name “wormwood.”60 The majority of
current research on wormwood revolves around its use as an
antiparasitic therapy. Artemisinin, an isolated compound of worm-
wood, has repeatedly proven to be effective in clearing two forms
of virulent malaria; in fact, it has been shown to be effective
against drug-resistant strains.78,79According to hospital controlled
clinical trials, artemisinin and its derivatives are the most rapidly
effective of all the antimalarial treatments.79
Herb Safety
In choosing herbal products for antimicrobial use, there are cer-
tain factors that should be considered. Foremost, because high
doses of active principles are required for an antimicrobial effect,
formulas should be combined properly to promote safety and effi-
cacy. In multi-herb formulas, the rationale for each plant should be
clearly stated. The correct species and safety of each plant should
be verified by routine independent testing for pesticides and/or
contamination. Whenever possible, a manufacturer’s Certificate of
Analysis should confirm extract specifications, herbs should be
standardized to provide levels of active principles congruent with
research and traditional use, and herb potency should be verified
by third party analysis.
Microbes including fungi, bacteria, viruses, parasites, and worms
will gladly infest and impede the function of the gastrointestinal
tract given the opportunity, leading to systemic manifestations of
all kinds. Plants, which must themselves combat infection and
predation, offer humans compounds with both specific and gener-
al actions that eliminate these microbes, while promoting the
health of the digestive system. By concentrating and utilizing phe-
nolic and alkaloid substances, effective and safe therapies can be
realized. While the aromatic phenols harmonize and cleanse the
gut and respiratory tract, alkaloid substances are best utilized to
harmonize and cleanse the gut and excretory organs including the
liver, gallbladder, and bladder. Substances such as garlic, worm-
wood, ginger, and sour plum can then be added to achieve greater
cleansing activity or to reduce the risk of acute infection, such as,
in the traveler. Furthermore, the concurrent use of prebiotics and
probiotics can help establish healthy gut ecology and support local
immunity. (Refer to CNI 505: Intestinal Health). From the
omnipresent threat and increasing incidence of intestinal infec-
tions, to the building scientific evidence of systemic diseases of
gut origin, intestinal health cannot be minimized as a priority in
modern health care.
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REFERENCES
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