There was a recent article in the
New York Times about gluten and celiac disease. Since then I have received a
lot of questions about this disease. In fact, it is the most commonly asked
question I hear when a patient comes in with bloating, gas and irritable
bowels. Though physicians have thought it was a rare diagnosis in the past, it
turns out that 1 in a hundred to 1 in three hundred of the U.S. population is
afflicted with this illness. The minority of celiac disease is diagnosed due to
mild disease without symptoms.
I came across a very interesting
article in Medscape Gastroenterology, March, 2013, by Dr. David Johnson, Professor of Medicine and
Chief of Gastroenterology at Eastern Virginia Medical School in Norfolk, VA. It is good, and would
like to share it with you.
From
Dr. David Johnson, Medscape Gastroenterology, March, 2013
Gluten-sensitive
enteropathy is something that we probably need to think more about. Patients
are all abuzz with this concept of gluten withdrawal, and they are saying,
"I feel better. What can you tell me about this?"
I
thought it would be helpful to review this topic. A recent article in the New
York Times [1] caught my
eye, and lo and behold, it was about an excellent article in the February issue
of Gastroenterology and Hepatology by William Chey's group[2] at the
University of Michigan. I thought it was time to take a look at the data and
put some science behind what is currently a field that is running without much
guidance.
What Is Gluten and What Is Celiac Disease?
First,
let's talk about gluten. Gluten is a component of wheat and wheat-related grain
products. When you start to talk about gluten withdrawal, is it really gluten
withdrawal or is it wheat-product withdrawal or grain-product withdrawal?
Grains are complex carbohydrates that have a number of fermentable sugars,
which we would frequently remove from patients' diets because most of them are
polyglycols -- fructans and galactans. We know from experience that when you
withdraw fermentable sugar from patients, they frequently have improvement in
symptoms such as bloating, gassy discomfort, and diarrhea.
Now
let's focus on celiac disease. The prevalence of celiac disease has increased
over the past several decades. Some inferential data suggest that some of it
may be related to the hybridization of wheat and related grain products over the
past several decades. We may actually be sensitizing more people, causing
gluten-sensitive enteropathy or non-celiac gluten sensitivity, which we will
discuss later.
We
found that gluten-sensitive enteropathy is responsive to gluten withdrawal, but
now we are seeing other patients who tell us that they feel better if they
withdraw gluten. And they have found this out by going on the Internet or
talking to friends and family who have had causal experience with this. Now we
have patients out there doing a variety of things on their own accord and
without a lot of medical judgment. That is not so good, particularly when you
start talking about withdrawal and restrictive diets.
Bottom
of Form
Who Is Affected by Gluten?
Is celiac disease more common in patients
with irritable bowel syndrome (IBS)? We
see a lot of overlap in the symptoms of gassy
discomfort, bloating, and diarrhea. Cash and colleagues[3] published an article in Gastroenterology in 2011 that looked at the prevalence of celiac disease
in patients with IBS symptoms and in those without symptoms but who underwent
routine colon screening or surveillance. No difference was found in prevalence
between the 2 populations. Interestingly, they did find increased markers for
an immunologic response to gluten with antibodies against tissue
transglutaminase (tTG), gliadin, and endomysium. They were increased with an
odds ratio of about 1.5 in people with IBS. Although they did not meet the criteria
for celiac disease, these patients were immunologically manifesting some
reaction to wheat-related products.
Does this mean that people who have
immunologic or some type of phenotypic predisposition to celiac disease have
more sensitivity to gluten? A very interesting article that was published about
a decade ago looked at patients who had some evidence of diarrhea-dominant
irritable bowel syndrome (d-IBS).[4] They looked at the response to gluten withdrawal and
found that there was a sizable percentage of people who had phenotypic markers
for celiac disease but did not manifest celiac when they did duodenal biopsies.
They were positive for the HLA-DQ2 or DQ8 phenotypic markers for celiac disease,
but for histologic manifestations they did not meet the criteria for celiac
disease. The investigators found that patients with other immunologic responses
(eg, antigliadin antibody positive or tTG positive) responded better to
withdrawal of gluten. In fact, a subset of patient populations with d-IBS will
respond to gluten withdrawal if they have immunologic predisposition by their
phenotype in addition to another immunologic manifestation, particularly the
IgG antibodies that you see against gluten.
What Is Non-celiac Gluten Sensitivity?
When we talk about non-celiac gluten
sensitivity, what are we talking about? We are talking about a patient
population that has some form of symptoms or morphologic response after
exposure to gluten, and they get withdrawal-related benefit. That would be
gluten-sensitive non-celiac disease. Associated symptoms have been described as
both classic intestinal (ie, gassy and crampy discomfort, bloating, and
diarrhea) and extraintestinal (ie, malaise, fatigue, or attention-deficit
disorder). An ataxic gait has also been described with gluten sensitivity.
Now let's take it a step further and ask: In
patients who have gluten sensitivity and who feel better after gluten
withdrawal, is it real or not real? In a very nice study[5] that was published about 2 years ago, investigators
looked at patients with d-IBS in whom all the serologic markers for gluten were
negative, but they felt better when they had gluten withdrawal. It was a
randomized, double-blind, placebo-controlled trial. They only had 34 patients,
but they were randomly assigned to receive bread and a muffin with gluten or
bread and a muffin without gluten.
At the end of 6 weeks, there was a
significant reduction of symptoms in the group that was receiving gluten-free
food compared with the group receiving gluten. Gluten withdrawal resulted in a
much more satisfactory response, with resolution of diarrhea, stool composure,
gassy discomfort, and pain from bloating. Fatigue was also improved, which is
interesting. I wonder if many of these patients were having sleep disruption at
night.
How Does Gluten Cause Problems?
How does gluten cause problems? In celiac
disease, it causes disruption of intestinal permeability, which is driven by an
upregulation of zonulin. Zonulin regulates intestinal permeability. However, no
such response is seen in gluten-sensitive non-celiac patients. Then why are
these people having problems? I am not ready to say that it's all gluten, but
gluten may be part of the problem.
Think about where we see gluten. It's in
wheat products and a variety of grain products. For IBS, fermentable sugars can
be reduced with the low-FODMAP (fermentable oligo-di-monosaccharides and
polyols) diet, which is a reduction in gluten. When you take fructans and
galactans -- the gluten or the related grain product itself with the
fermentable sugars -- and dump them into an environment that is rich with
intestinal flora that can ferment these sugars, you change osmotic load and you
change intestinal fluids. You may change upregulation with sensitivity and
motility changes, and there may also be microflora changes as you start to have
a more acidic environment and you begin to manifest complex short-term fatty
acids. These may change the intestinal flora, so it is difficult to say that
everything is related to wheat and specific to gluten until we have better
trials.
Testing and Treatment
What should we do with these people? If you
have a patient who has diarrhea, gas, and bloating, it's very reasonable to do
serologic testing. I think celiac disease is still missed in many patients. If
you have a celiac patient who is negative for the standard profile and still
has symptoms, it's reasonable to do HLA typing and the DQ2 or DQ8 profile. It
would certainly give you an idea of whether this patient may do better after
withdrawal of gluten, particularly if you could combine it with another marker.
If the patient is antigliadin positive and tTG positive, start to look at
phenotypic markers as well.
In trying to make patients totally
gluten-free, it is very challenging to tell them to be totally restrictive. In
my practice, I refer them to a nutritionist. There is very strong evidence that
when patients are left on their own, a variety of macro- and micronutrient
deficiencies can develop. If you are a patient, talk to your doctor. As a
physician, I refer these patients to a nutritionist. It has been estimated that the industry is shifting
to meet this market with approximately $6 billion in gluten-free products. We know that gluten is not only in food
products but in things like beer, cosmetics, and postage stamps. The industry
is shifting to meet the need, and fanning the fire is the patient's
recollection that he feels better without gluten.
The science is there. It is beginning to
emerge. It does make sense, but not in everybody, so be aware of it. Talk to
your patients and look hard at potentially finding markers for whether they are
more likely to have a response.
These patients are no longer lacking the
ability to go out and find gluten-free foods or products. If they are truly
celiac, then they have to be a line reader. But for people with non-celiac
gluten sensitivity, it remains to be seen how much of an antigenic response
will be necessary to truly make the patient feel better. I think it's real. We
need to pay attention, we need to be a little bit more pragmatic, and our patients
will benefit from this as we learn.
