functional medicine and nutritional genomics - American Association ...

AAPI’S NUTRITION GUIDE TO OPTIMAL HEALTH: USING PRINCIPLES OF FUNCTIONAL MEDICINE AND NUTRITIONAL GENOMICS
enriched foods, such as, fermented vegetables
(sauerkraute) and milks (kefirs) are used to
improve the status of human microbiota. However,
research has shown human microbiota are resilient
and may be resistant to change with probiotic
supplements having the smallest effect on global
microbiota change (1%) followed by specific diet
strategies (5%). The largest effect on microbiota
composition in the human intestine is through
microbial transplantation (up to 100%)[33]. Thus
far, gut microbiota seem to be quite stable and
are easily restored, so even the small effect of
probiotic supplementation has not been shown to
last long [34, 35]. Microbial transplantation has
shown the greatest effect on restoring gut
microbiota. With further research, microbial
transplantation may become the therapy of choice
to restore a healthy gut [36].
Celiac disease is a partially inherited, life-long
intolerance to gluten. The disease was traditionally
defined as a gastrointestinal malabsorption disorder
but we know recognize that manifestations of the
disease are highly variable [37]. It is most
certainly an inflammatory-related disorder in which
gliadins, toxic peptides in gluten, pass through the
epithelial barrier of the intestine generating an
immune response that cascades into an
inflammatory reaction guided by CD4+T cells
bound to HLA DQ2 and HLA DQ8 molecules on
antigen presenting cells[38]. The major
environmental factor in celiac disease, gluten,
found in wheat, barley and rye; was identified 60
years ago when Dr. W.K. Dicke published a paper
that described the improvement of symptoms in
celiac children when wheat, rye and oat flour had
limited availability in the diet, during World War II.
Approximately 1% of the global population has
received a celiac disease diagnosis (current
estimates), for which positive serum antibodies
and an intestinal biopsy indicative of villous
atrophy are required. However, many celiacs
remain undiagnosed; some of whom are likely to
have silent disease in which gastrointestinal
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symptoms are absent, or other less obvious
manifestations; such as neurologic symptoms or
dermatitis herpetiformis[38].
Alleles that comprise the HLA DQ2 and 8
phenotypes associated with celiac disease
susceptibility were identified over 30 years ago;
and celiac disease does not develop unless an
individual possesses one of various combinations
of these alleles. However, 40% of the population
has these genetic markers, and the contribution of
the HLA genes to the genetics of celiac disease
is less than 50% [39]. The additional contribution
to disease manifestation could be additional,
unidentified gene x gene interactions or
environmental interactions, such as excessive
gluten intake over a prolonged period of time.
Genome Wide Association Studies (GWAS) have
been conducted to examine additional genetic
contributors to disease susceptibility and
manifestations. Data have been collected on
thousands of celiac patients and controls to
compare non-HLA SNP frequencies. Approximately
39 non-HLA celiac disease risk loci have been
identified, including multiple genes of obvious
immunological functioning [40]. Since individuals
with celiac disease are at risk of developing other
autoimmune diseases, there is a particular interest
in genes shared by autoimmune diseases and
celiac disease. Thirty one unique genetic loci have
been identified of which 14 are shared between
celiac disease and rheumatoid arthritis. These
shared genes are also implicated in T cell antigen
presentation[41].
It is a common misconception that we wake up
one day and have a chronic disease. The body
needs to go through a period of progressive
dysfunction first, that will ultimately result in
disease diagnosis if it is not rectified. For
individuals with celiac disease, a life-long, gluten
free diet can prevent the development of other
auto-immunities, however, quality of life is lower,
2012