EXCERPTED FROM POWER HEALING (RANDOM HOUSE, 1998)
BY LEO GALLAND, M.D.
In keeping with its immense surface area and intense exposure to foreign antigens,
the intestinal tract is the largest organ of immune surveillance and response
in the human body (Targan et al., 1987). It should not be surprising
that events occurring in its lumen or on the mucosal surface have systemic effects
on immune function and disease resistance. This chapter examines the contribution
made by luminal organisms commonly encountered in humans: bacteria, protozoa
and yeasts. Particular attention win be given to data concerning a role for
Giardia lamblia infestation and Candida albicans colonization
in the pathogenesis of chronic fatigue and immune dysfunction.
Over 500 species of bacteria live in the healthy human alimentary canal; in
the average adult they weigh about one kilogram. The normal colonic microflora
ferment soluble fibre to yield short-chain fatty acids which supply 5-10% of
human energy requirements (McNeil, 1984). Endogenous flora synthesize at least
seven essential nutrients, supplementing dietary intake: folic acid, biotin,
pantothenic acid, riboflavin, pyridoxine, cobalamin and vitamin K (Mackowiak,
1982). They participate in the metabolism of drugs, hormones and carcinogens,
including digoxin (Lindenbaum et al., 1981), sulphasalazine, and estrogens
(Gorbach, 1982). By demethylating methylmercury, gut flora protect mice from
mercury toxicity (Rowland et al., 1984). They prevent potential pathogens
from establishing infection by numerous mechanisms, which include: production
of short-chain fatty acids and bacteriocin, induction of a low oxidation-reduction
potential, competition for nutrients, deconjugation of the bile acids (which
renders them bacteriostatic), blockade of adherence receptors and degradation
of bacterial toxins (Savage, 1980).
Germ-free animals have mild to moderate defects in immune function when compared
to control animals. These include lower levels of natural antibodies, hyporesponsive
macrophages and neutrophiles, defective production of colony-stimulating factors,
leukopenia, lymphoid hypoplasia, subnormal interferon levels and weak delayed
hypersensitivity (DHS) responses. They are more susceptible to infection with
intracellular parasites such as Listeria, Mycobacterium and Nocardia,
but are not more susceptible to viral infection (Mackowiak, 1982). Adverse effects
of endogenous bacteria have also been described, indicating the complexity of
the host-saprophyte relationship. In diseases where host immune response is
the primary cause of pathology, such as lymphocytic choriomeningitis, germ-free
animals fare better than control animals (Mackowiak, 1982).
The immunologic effects of normal gut flora are in part due to antigenic stimulation
and in part to the bacterial origin of specific immune activators, such as endotoxin
lipopolysaccharicle (LPS) and muramyl dipeptides Worrison and Ryan, 1979; Mackowiak,
1982; Stokes, 1984). An important role for these substances in normal immune
regulation has not been established, however (Mayrhofer, 1984).
The gut flora of healthy individuals is very stable (Sears et al., 1950,19-%);
this stability may in part be due to interbacterial inhibition (Sprunt and Redman,
1968). Alteration in the level of normal flora by antibiotics has long been
known to allow secondary infection by pathogenic bacteria and yeasts (Keefer,
1951; Seelig, 1966).
Occasional publications describe abnormal fecal flora in patients with atopic
eczema. Kuvaeva et al. (1984) studied 60 infants in Moscow with IgE mediated
food allergy and eczema. They reported a decrease in anaerobic bacteria and
lactic acid-producing aerobes and an increase of Enterobacteriaceae. Severity
of eczema was directly proportional to severity of dysbiosis. No control data
are given. Ionescu et al. (1986) studied fecal flora in children and
adults with atopic eczema. Compared with healthy controls, there was a marked
reduction in Lactobacillus, Bifidobacterium and Enteroccoccus species
in the great majority of cases. This was associated with increased concentrations
of Candida species, Proteus, Klebsiella, and Staphylococcus
allreus, and appearance of atypical coliforms and Clostridium innocutan.
The high frequency of hypoalbumenernia, indicanuria and steatorrhea in the eczema
group suggested small bowel bacterial overgrowth with secondary malabsorption.
In neither of these studies is it possible to determine whether abnormal bowel
flora caused allergy or whether food-allergic disease destabilized gut flora.
Immunologic reactions to normal or abnormal components of the bacterial gut
flora are implicated in the etiology of some inflammatory disorders. Reactive
arthritis may occur after intestinal infection with Salmonella typhimurium,
Yersinia enterocolitica serotype 3, Shigella flexneri, Campylobacter
jejuni and Clostridium difficile (Inman, 1988). Because arthritogenic potential
is strain-specific and because 60-80% of patients with reactive arthritis carry
the HLA-B27 gene, it is likely that genetically determined antigenic crossreactivity
plays a role (Yu et al., 1989).
Ankylosing spondylitis (AS) occurs almost exclusively in HLA-B27positive individuals.
An increased rate of intestinal colonization with Klebsiella pneumoniae
has been described in this condition, according to some but not all studies
(Kinsella, 1988). Immunologic cross-reactivity has been shown for HLA-B27 antigen
expressed on the host cell membrane and antigens present in K. pneumoniae,
S. flexneri and Y. enterocolitica, suggesting molecular mimicry in
the pathogenesis of this disease (Yu, 1988). Workers in Australia have demonstrated
bacteria with cross-reactive antigenic determinants in bowel flora of B27-positive
AS patients; these bacteria are almost never found in B27-positive controls
without AS (McGuignan et al., 1986).
Endotoxemia has been described in patients with psoriasis (Rosenberg and Belew,
1982a) and cystic acne (Juhlin and Michaelson, 1984). Activation of the alternative
complement pathway (APC) by gut-derived endotoxin may play a role in the pathogenesis
of these disorders. Exposure of macrophages to endotoxin causes release of cytokines,
such as interleukin-1 (Il-1) and tumor necrosis factor (TNF). These peptides
have powerful effects on the immunologic and metabolic response to infection.
Whether gutderived endotoxins influence cytokine production in vivo is
Although it was first described by van Leuwenhoek in 1681, it is only in the
past 25 years that G. lamblia has been acknowledged as an important pathogen
(Gillon, 1984). Giardiasis is the commonest cause of parasitic disease in the
United States (Myer and Jarroll, 1980) with an overall prevalence estimated
at 7.4%, which is about the same as its average worldwide prevalence (Mahmoud
and Warren, 1975). Prevalence in Great Britain varies from 2% to 10% (Felman
and Nikitas, 1985). At least 27% of Giardia infections identified at
the University of Edinburgh Medical School had been acquired within the UK and
a diagnosis of giardiasis had not been suspected in two-thirds of cases (Gibb,
Reports based on stool screening may underestimate the prevalence of giardiasis.
Comparison of stool examination with duodenal aspiration has consistently shown
that stool examination fails to identify infected patients even at the height
of acute infection. Single stool specimens have a sensitivity of zero (Rosenthal
and Liebman, 1980) to 50% (Kamath and Murugasu, 1974). Collecting multiple specimens
over several days increases the sensitivity to 85-90% (Gillon, 1984).
To overcome the limitations of stool analysis we developed a diagnostic technique
by which rectal mucus obtained at anoscopy is stained with a monoclonal antibody
to Giardia cysts and examined by epifluorescence microscopy (Galland
and Bueno, 1989). We recently conducted a two-year retrospective study of 218
patients who presented to our medical clinic with a chief complaint of chronic
fatigue (Galland et al., 1990). G. lamblia infection was identified by
rectal swab in 61 patients. The symptoms of patients with and without giardiasis,
are shown in Table 1.
All patients with giardiasis and 86% of patients without giardiasis complained
of digestive symptoms, but these were generally mild. The most interesting difference
between the two groups lies in the positive association between giardiasis and
symptoms such as myalgia, muscle weakness, flu-like feelings, sweats and adenopathy.
In fact, 61% of fatigued patients with giardiasis had been diagnosed elsewhere
as suffering from chronic fatigue syndrome (CFS) or ME, compared to only 19%
of fatigued patients without giardiasis. Cure of giardiasis resulted in clearing
of fatigue and related 'viral' symptoms (myalgia, sweats, flu-like feelings)
in 70% of cases, some palliation of fatigue in 18%, and was of no benefit in
12%. This study shows that giardiasis can present with fatigue as the major
manifestation, accompanied by minor gastrointestinal complaints and sometimes
by myalgia and other symptoms suggestive of ME. It indicates that G. lamblia
infection may be a common cause of CFS, at least in the United States. It is
noteworthy that tricyclic antidepressants, a standard treatment for CFS, suppress
the growth of Giardia in vitro (Weinbach et al., 1985).
The mechanism by which G. lamblia causes disease is not known. Experiments
with human volunteers demonstrate that the ability of Giardia to produce
infection and to cause diarrhea depends upon the strain of G. lamblia
used (Nash et al., 1987), the inoculum dose (Rentdorff, 1954; Rentdorff
and Holt, 1954), and previous exposure to the organism (Nash et al., 1987).
Heterogeneity of Giardia isolates from humans in the same city occurs
and has been proposed as one mechanism for variability of clinical response
to infection (Korman et al., 1986).
Systemic symptoms of CFS patients
(%) (N = 63)
(%) (N = 157)
|Poor exercise tolerance