Yeast (Candida, Saccharomyces)
Yeast cells such as
Candida spp.
and
Saccharomyces spp.
may exist in more than one form [Shaw2008].
The hypha form is a more invasive colony-forming form that invades
the lining of the gastrointestinal tract and secretes digestive
enzymes that damages the wall of the gastrointestinal tract and
possibly protective immunoglobulin-A (IgA)
[Banno1985],
[Pugh1975].
This damage may lead to Leaky Gut Syndrome
and decreased secretion of the hormone secretin [Shaw2008].
Another form that yeast can take is the cell-wall deficient form [Shaw2008].
Clostridium
The bacteria
Clostridium tetani
is known to produce a potent neurotoxin that causes rigid paralysis.
Individuals with tetanus have extreme sensory sensitivity to light and noise, and have trouble
chewing and swallowing, similar to some cases of autism [Shaw2008]
[Crone1992]
[Ogunyemi1986].
Subacute infections of Clostridium tetani in the gut have been reported
[Wells1983].
The bacteria
Clostridium botulinum
is known to produce a potent neurotoxin that causes flaccid paralysis.
The mechanism of action of
Clostridium spp.
neurotoxins has been discussed [Montecucco1994] and it has been pointed out that
the structural gene for the Clostridium spp. neurotoxin is located on a plasmid,
which allows for transfer of this toxin-producing gene from one species of Clostridium
to another [Finn1984].
Furthermore, the toxins produced by
Clostridium tetani,
Clostridium botulinum,
Clostridium baratii
and
Clostridium butyricum
are all very similar [Finn1984].
Many other species of Clostridium are known to contribute to dysbiosis,
so it is reasonable to consider the possibility that some of these bacteria
might produce neurotoxins capable of producing the symptoms of autism or ADD.
Because Clostridium spp. are strict anaerobes, they are very difficult
to isolate and culture. Hence they are poorly characterized [Shaw2008].
Antibiotic treatments that tend to promote overgrowth of Clostridium spp.
are often observed to worsen the symptoms of autism and ADD,
while antibiotic treatments that tend to kill Clostridium spp.
are often observed to improve these same symptoms
[Sandler2000], [Shaw2008].
According to research by Walter Gattaz and William Shaw, HPHPA,
a metabolite derived from Clostridium spp. metabolism is found in
unusually high levels in the urine of patients suffering from
schizophrenia, autism, and also intestinal overgrowth of
Clostridium difficile
[Shaw2008]. HPHPA and other metabolites
of the metabolism of Clostridium spp. are detectible by the
Organic Acid Test.
One possible explanation for the neurotoxicity of Clostridium spp.
is their ability to metabolize the essential amino acid phenylalanine via
microbial meta-hydroxylation of phenylalanine to form
3-hydroxyphenylalanine (an analog of tyrosine, which is 4-hydroxyphenylalanine),
which is then further processed
by the human biosynthetic pathways to form 3,5-dihydroxyphenylalanine
(an analog of 3,4-dihydroxyphenylalanine, which is also known as
the neurotransmitter precursor called L-dopa).
This L-dopa analog is then further metabolized by human biosynthetic
pathways to analogs of the neurotransmitters dopamine, norepinephrine,
and epinephrine [Shaw2008, pg 14].
Administration of 3-hydroxyphenylalanine (tyrosine analog) to rats has been
observed to result in a characteristic behavioral syndrome in rats consisting
of forepaw padding, head weaving, backwards walking, splayed hind limbs,
wet dog shakes, hyperactivity and hyperreactivity, as well as depletion of
the catecholamine neurotransmitters in the brain and elevation of the
dopamine analog (homovanillic acid, HVA) in the urine
[Dyck1982], [Shaw2008].
Another possible explanation for the neurotoxicity of Clostridium spp.
is their ability to deaminate the essential amino acid phenylalanine
to form phenylpropionic acid, which is an inhibitor of the enzymes in the
brain that metabolize endogenous opioids such as enkephalins and endorphins
[Giusti1985],
[Blum1987].
It has also been hypothesized [Shaw2008] that some metabolite of
Clostridium spp. may interfere with the normal conversion of
dopamine to norepinephrine and epinephrine, based on the observation that
the ratio of the dopamine analog metabolite homovanillic acid (HVA)
to the norepinephrine/epinephrine metabolite vanillylmandelic acid (VMA)
is elevated in the organic acid test
when HPHPA is elevated. Blocking the normal conversion of dopamine into
norepinephrine would result in a build-up of excess dopamine, which is
associated with the hyperactivity and stereotypical behaviors as are found
in autism. Note that drugs such as phenothiazines and haloperidol, which are
used to treat autism, block the dopamine receptor [Shaw2008].
Caution may be indicated in the use of phenylalanine supplementation in the
presence of Clostridium spp. dysbiosis, as this may result in an
exacerbation of the build-up of dopamine [Shaw2008].
Clostridium spp. are spore-forming bacteria, which means that under
adverse conditions, e.g. antibiotic therapy, they can encase themselves
in a hard shell and go to sleep until more suitable conditions return.
Thus it is not unusual to experience a relapse after removal of antibiotic
therapy.
The addition of probiotics (beneficial bacteria that competitively suppress
Clostridium spp.) is a useful adjunct to antibiotic therapy
[Gorbach1987]. While the probiotic
Lactobacillus acidophilus GG is reported to give good results, other
probiotics are reported to be less useful [Shaw2008].
SIBO
is a special case of intestinal dysbiosis that is characterized by an overgrowth
of bacteria in the small intestines.