may sleep poorly and feel fatigued. Doctors have therefore
surmised that the mood problems must be a direct cause of the
stomach symptoms they experience after eating.
But what if it’s the other way around? What if, in some cases,
there is an underlying problem that leads to symptoms we call
functional dyspepsia, and this stomach problem causes alter-
ations in the brain that manifest as anxiety, depression or fatigue?
There is now such evidence emerging, leading to the exciting
possibility we may be able to ix not only indigestion but also
mood disorders in some people.
When you look down into the stomach and upper intestine
with an endoscope in a patient with functional dyspepsia it
looks normal. But is it? We asked ourselves if we could be
missing subtle microscopic changes overlooked by pathologists
in the small tissue biopsies taken through the endoscope.
Think about even a really small skin boil, and remember
how red, painful and unpleasant this can be because of the
inlammation from the cells and chemicals marshalled into the
small area. Could similar inlammation have been missed in
the intestine?
This has happened before. Pathologists routinely failed to see
the bacteria that cause stomach ulcers and stomach cancer and
the inlammation all around the bacteria was ignored, even
though the indings were all plain to see in the biopsy tissue –
you tend to see what you expect and are trained to see, and no
more! Only after Robin Warren and Barry Marshall in Perth
published their discovery of the bacteriumHelicobacter pylori
did other pathologists start noticing them. Marshall and Warren
won the Nobel prize for their discovery.
So we undertook a unique study in northern Sweden, inviting
people from a local community during the winter when there
was not much to do to visit a local clinic and have a free look
down into the stomach, including taking tissue biopsies (which
is painless). All we offered was a free T-shirt, yet 80% of thoseapproached agreed to take part in the study. We enrolled 1000
volunteers, whether they had bad stomach symptoms or none
at all. And we looked very carefully at the biopsies, in particular
the samples from the upper intestine because we suspected we
would ind increased cells that would signal the presence of a
speciic type of allergic inlammation.
We were right: we found that pathologists had been missing
subtle changes in the upper intestine. When we counted the
number of cells in the duodenum there were increased numbers
of eosinophils. These special white blood cells are normally
recruited to help ight parasites and inlammation but are also
seen in allergic conditions.
In studies from around the world, including in Australia, we
have conirmed these indings. We had discovered a new disease
in adults that appeared to account for a large number of cases
of the mysterious disorder functional dyspepsia, which we have
renamed duodenal eosinophilia. The pathology we can observe
is a bit like the microscopic changes seen in the lung in cases of
allergic asthma.
We now have evidence that the eosinophils in people with
functional dyspepsia can break down and release toxic prod-
ucts near nerves in the gut. This must alter the functioning of
the nerve and muscle, leading to symptoms.
Circulating chemicals called cytokines are released into the
bloodstream too. Cytokines make you feel sick and tired, and
the circulating cytokines we observed are strongly linked to
anxiety in people with abdominal troubles.
In other words, we now have direct evidence that changes in
the upper intestine near the stomach are likely to cause brain
symptoms such as anxiety and possibly fatigue and sleep distur-
bances.
In long-term follow up studies of people with and without
symptoms, we have observed that some people will develop
new stomach symptoms and then, for the irst time ever, develop
anxiety, providing further evidence that a stomach disturbance
can be the cause of brain symptoms.
It goes the other way too. Anxiety can develop initially and
then the stomach symptoms can begin after stomach function
becomes newly disturbed. Knowing what happens irst may
help doctors decide whether to treat the stomach or the brain
initially.
Having discovered that cells linked to allergy are present in
functional dyspepsia, we have found that people with these
same indigestion symptoms are also more likely to suffer with
asthma or allergic skin rashes. Certain foods people eat, like
wheat, may be important in setting off the intestinal inlam-
mation in some cases, although proving that wheat intolerance
is a cause has not yet been completed.
We have also observed that people exposed to horses or
similar pets are more at risk of developing bad indigestion,28 | APRIL 2016
Eosinophils (stained orange) can break down in the upper
intestine and release toxins that affect gut functioning.