October 25, 2000
A Look at 'Leaky Gut' Theories of Autism
* The Concept of Increased Intestinal Permeability
* Gastrointestinal Abnormalities Among Children with Autism
* Binstock's Anterior Insular Cortex Hypothesis for Linkage
Between Gut and Brain
[These summaries of "Leaking Gut Theories" of autism are written and
maintained by Lewis Mehl-Madrona, M.D., Ph.D., Medical Director of The
Center for Complementary Medicine. Email coyotemd@earthlink.net Other
theory of autism summaries are also available at the website below.
References have been deleted but are available at the website. This
material contains technical language.]
http://www.healing-arts.org/children/
The Concept of Increased Intestinal Permeability
The concept of increased intestinal permeability is key to many
theories of autism. Just how important is the integrity of the intestine's
mucosal lining to good health? In children in remote tropical regions
without access to adequate medical care, progressive damage to the gut's
barrier function can eventually lead to life-threatening conditions,
requiring them to be airlifted for emergency medical treatment.
Aboriginal children in Australia, for example, have high rates of
severe intestinal diseases, or enteropathies, that cause chronic diarrhea.
These conditions can lead to dehydration, acidosis, and hypokalaemia -
serious complications associated with central nervous system damage and even
death.
To shed more light on how these conditions develop, researchers from
Australia evaluated intestinal permeability (IP) in Aboriginal children,
measuring the rate that two nondigestible sugars are excreted in urine after
ingesting a challenge drink. This noninvasive test indicates the gut's
ability to absorb nutrients and to block toxins, bacteria, allergens, and
other potentially harmful molecules from penetrating into the systemic
circulation.
The IP ratio for Aboriginal children with diarrhea was, on average,
more than twice as high as that found in their healthy Aboriginal peers.
When compared with healthy non-Aboriginal children, these Aboriginal
children with diarrhea showed an IP ratio over three times higher than
normal. An elevated ratio of larger molecules such as lactuolose to smaller
sugar molecules such as mannitol or rhamnose, recovered in the urine sample,
indicates increased permeability and mucosal damage. This value is known as
the IP ratio.
Surprisingly, a higher IP ratio was found even in healthy Aboriginal
children without diarrhea. Researchers speculated that this increased
permeability - double that normally found in healthy non-Aboriginal
children - was "consistent with an underlying partial villous atrophy," a
wearing down of the finger-like projections on the intestine's mucosal
layer, caused by environmental factors. For this reason, the Aboriginal
children were more susceptible to gastrointestinal diseases and their
complications.
How does this all happen? One possible mechanism involves the body's
digestion of milk products. Increased IP may reflect damage to the
microvilli, which can reduce levels of lactase, the enzyme needed to digest
milk sugar, eventually triggering osmotic diarrhea. Once this disease
process starts, small bowel mucosal damage, indicated by higher IP ratios,
remains "an important factor" associated with increased acidosis,
hypokalaemia, iron deficiency, dehydration, and parasitic infection.
Great Smokies Diagnostic Laboratory offers an Intestinal Permeability
Assessment. This test is a noninvasive and convenient way to evaluate gut
mucosal barrier function in patients with chronic gastrointestinal disorders
or in those individuals with a higher likelihood of developing such
problems, including patients with chronic inflammatory conditions,
especially those using NSAIDS. I use it with my autistic children and
monitor the effectiveness of my treatment to reduce intestinal permeability.
Two physicians have written articles that are posted on the Great
Smokies' web site: Inflammatory Conditions and the Gastrointestinal Tract,
by Myron Lezak. M.D., and Leaky Gut Syndrome: A Modern Epidemic, by Jake
Paul Fratkin, O.M.D. Both discuss aspects of intestinal permeability and the
conditions related to impaired mucosal function.
I suspect intestinal permeability is very important for autistic
children, and that the assay should be routinely used as a means of
following the success of therapies for autism.
* *
Gastrointestinal Abnormalities Among Children with Autism
Horvath, et al. (1999)29 evaluated the structure and function of the
upper gastrointestinal tract in a group of patients with autism who had
gastrointestinal symptoms. Thirty-six children (age: 5.7 ± 2 years, mean ±
SD) with autistic disorder underwent upper gastrointestinal endoscopy with
biopsies, intestinal and pancreatic enzyme analyses, and bacterial and
fungal cultures.
The most frequent gastrointestinal complaints were chronic diarrhea,
gaseousness, and abdominal discomfort and distension. Histologic examination
in these 36 children revealed grade I or II reflux esophagitis in 25
(69.4%), chronic gastritis in 15, and chronic duodenitis in 24. The number
of Paneth's cells in the duodenal crypts was significantly elevated in
autistic children compared with non-autistic control subjects. Low
intestinal carbohydrate digestive enzyme activity was reported in 21
children (58.3%), although there was no abnormality found in pancreatic
function. Seventy-five percent of the autistic children (27/36) had an
increased pancreatico-biliary fluid output after intravenous secretin
administration. Nineteen of the 21 patients with diarrhea had significantly
higher fluid output than those without diarrhea.
The authors concluded that unrecognized gastrointestinal disorders,
especially reflux esophagitis and disaccharide malabsorption, may contribute
to the behavioral problems of non-verbal autistic patients. The observed
increase in pancreatico-biliary secretion after secretin infusion suggested
an upregulation of secretin receptors in the pancreas and liver.
* *
Binstock's Anterior Insular Cortex Hypothesis for Linkage Between Gut
and Brain.
Binstock (http://www.jorsm.com/~binstock/insular.htm) has developed a
hypothesis to explain the gut-brain relationships for autistic children.
The anterior insular cortex (aIC) links visceral sensation from the
gastrointestinal tract with the amygdala and the hypothalamus. The anterior
insular cortex also participates in oral phenomena, object recognition, and
naming along with "apraxia of speech".
Twenty-five stroke patients with articulatory deficits all had a
lesion within "a discrete region of the left precentral gyrus of the
insula", whereas this area was "completely spared" in 19 stroke patients
without these deficits.
Autism-spectrum children with atypical oral habits and/or disorders of
naming and of language also tend to have a typical gastrointestinal
symptoms. There is also a growing volume of anecdotal data that a small
subgroup of autism-spectrum children experiences improved sound production
and language use in response to treatments whose focus and effects are
gastrointestinal. These treatments include gluten-free and casein-free
diets, anti-Candida therapies, anti-viral therapies, and antibiotic
therapies suggesting that the underlying neuronal circuitry is intact.
Binstock suggests that the aIC and associated nuclei could become
disrupted by at least two mechanisms: (I) intraneuronal migration of a
neurotropic virus and/or (II) chronic hyperstimulation of the
gastrointestinal tract.
Gesser and colleagues have documented (I) the translocation of HSV
from the gastrointestinal tract into the mesenteric nervous system (rats and
humans), and (II) the migration of mesenteric HSV as far as theamygdaloid
nuclei in rats. In this theory, viruses could migrate from the
gastrointestinal tract through neural pathways into the central nervous
system.
Given a high rate of stimulation of neuron pathways reporting
gastrointestinal conditions to limbic regions and cortex, neurotransmitter or
intracellular-messenger use in excess of their production or recirculation
could occur, thereby inducing a change of function of neurons within the
aIC.
This hypothesis provides a basis for helping autistic children through
treating their gastrointestinal disturbances.
Source: FEAT Daily News
