Roger M Batt BVSc, MSc, PhD, MRCVS, DipECVIM-CA
Head of Veterinary Research
Waltham Centre for Pet Nutrition
INTRODUCTION
Pancreatic and intestinal disorders occur commonly
in dogs. Signs usually include diarrhoea with or without vomiting, but
changes in appetite, increased bowel sounds, excessive intestinal gas and
abdominal discomfort may also be seen. Chronic pancreatic and intestinal
disease may result in the so-called malabsorption syndrome, which is mainly
characterised by weight loss and diarrhoea. Weight loss is occasionally
the main or only sign noticed by the owner.
German shepherds dog appear to have an increased
risk of chronic pancreatic and intestinal disease compared with other dog
breeds. The exact cause of this is unknown but there is growing evidence
that some dogs may have an immune deficiency, which predisposes them to
developing intestinal disorders as well as chronic infections. In this
article an overview is given of the pancreatic and intestinal diseases
that are commonly seen in German shepherd dogs, and their possible causes
and treatment.
COMMON INTESTINAL DISEASES
Acute versus chronic diarrhoea
Acute diarrhoea is quite common in the dog, but
the actual cause is often not defined. In most cases it is probably due
to dietary causes such as overeating or a sudden change of diet. The possibility
of parasites should not be overlooked, especially in young dogs. Intestinal
viral infections usually cause transient vomiting and diarrhoea; parvovirus
used to cause more severe signs but is no longer a common problem. Bacterial
infections such as Salmonella or Campylobacter occasionally cause severe,
acute diarrhoea, which is more likely to occur in young and/or stressed
animals. Most dogs with mild, acute diarrhoea respond well to dietary restriction
alone and need no further measures taken, although young dogs should have
their stool examined for parasites and be treated if necessary.
Chronic diarrhoea can be much more of a problem.
It is unlikely to resolve on its own and usually requires further testing
in order to determine the underlying cause (Tables 1 and 2). However, during
recent years major advances have been made in the understanding of canine
gastrointestinal diseases, and new and more sensitive tests have become
available. These advances have particular importance for the German shepherd
dog, in which several of these diseases are prevalent.
Exocrine pancreatic insufficiency (EPI)
What causes EPI?
EPI in dogs is most frequently due to pancreatic
acinar atrophy, which is a condition uniquely common in the dog. It is
characterised by a progressive loss of the pancreatic cells that normally
produce powerful enzymes required for the initial degradation of food in
the small intestine. In EPI, fewer and fewer of these digestive enzymes
are produced, which ultimately leads to maldigestion and malabsorption
of nutrients. The situation is compounded by the fact that there may be
secondary gut damage, whereas EPI also predisposes the animal to the development
of small intestinal bacterial overgrowth (SIBO), which has an additional
negative effect on intestinal function.
The underlying cause of pancreatic acinar atrophy
is unknown. There is a high prevalence of EPI in German shepherd dogs,
in which breed the disease is reported to be heritable in an autosomal
recessive manner. A recent study has indicated that the pancreatic atrophy
is preceded by lymphocytic-plasmacytic inflammation, which suggests that
the disease may have an immune component. However, these are very preliminary
findings, and at present we have to assume that there is no definite cause,
and treatment remains symptomatic.
Signs
EPI may occur in a wide variety of dog breeds
and at any age, but two-third of EPI-cases in the UK are German shepherd
dogs. It typically presents in young adult dogs between 1 and 5 years of
age. Signs are ravenous appetite, weight loss despite the increased appetite,
and diarrhoea. Stools are voluminous, poorly formed and greasy-looking.
The hair coat is often in poor condition.
How to diagnose EPI
Since treatment of EPI requires lifelong replacement
therapy and judicious dietary management, an exact diagnosis is important.
Fortunately, this has been greatly facilitated by the availability of the
TLI-test. This is a simple, reliable and sensitive blood test, which measures
the amount of a pancreatic digestive enzyme (trypsinogen) in the blood
stream, providing an excellent indirect assessment of pancreatic function.
Dogs with EPI can be identified by a low blood TLI concentration. Marked
reductions in serum TLI concentration may precede the onset of clinical
signs of EPI, and assay of serum TLI has thus been useful for the early
identification of affected dogs. The TLI-test has replaced stool digestion
tests, which are insensitive and unreliable.
Treatment of EPI
Most dogs with EPI can be managed successfully
by supplementing each meal with pancreatic enzymes. Pancreatic powdered
extract seems to work best in the dog. In addition, a highly digestible,
moderately fat-restricted diet should be fed, which helps to overcome residual
digestive deficits. Vitamin B12 supplementation should be given to dogs
with low blood concentrations of this vitamin. Additional treatment,
for instance antibiotic treatment for bacterial overgrowth, may be required
in dogs that do not respond to standard management.
With adequate treatment, the outlook for dogs
with EPI is usually good, although the cost of enzyme replacement can be
substantial since dogs will require life-long treatment.
Small intestinal bacterial overgrowth (SIBO)
What causes SIBO?
The small intestine normally contains relatively
few bacteria. Under certain circumstances there can be an increase in intestinal
bacteria, which then may interfere with normal intestinal function. Bacteria
can damage the intestinal mucosa (i.e. the lining of the gut), resulting
in diarrhoea and weight loss, and they can also metabolise food components
within the intestine, thus aggravating the weight loss.
SIBO may develop if the gut’s normal defence
mechanisms are impaired. In people, it usually happens because there is
decreased flow of intestinal contents due to partial obstruction, but this
seems rarely to be the case in the dog. In dogs, SIBO was first described
in 1983 as the cause of an enteropathy in German shepherd dogs. Since then,
it has emerged as a common and important cause of chronic diarrhoea and/or
weight loss in many dog breeds, although it is still decidedly more common
in German shepherd dogs.
Dogs may develop SIBO secondary to EPI or gastrointestinal
motility problems such as partial obstruction. It may also be a secondary
complication of existing intestinal disease such as inflammatory bowel
disease, where it is due to altered local immunity. Potentially, it may
also occur when gastric acid production is reduced (for instance following
prolonged treatment with acid-blockers), which makes the conditions in
the upper small intestine less acid and more favourable for bacterial growth
(Fig. 1). However, in many cases no underlying cause can be identified.
A primary or idiopathic form of SIBO is prevalent in young dogs; there
is a predominance of German shepherd dogs, in which there is now good evidence
that it is related to a mucosal immune deficiency. Many German shepherd
dogs with bacterial overgrowth have low blood levels of IgA, which is an
important immunoglobulin for mucosal defence. Intestinal IgA has been likened
to an anti-absorptive paint; its primary function is to prevent antigens
from bacteria, viruses and food from crossing the gut barrier. IgA-deficiency
may thus predispose German shepherd dogs to SIBO and also to other, systemic
infections. However, studies have been hampered by the fact that IgA in
blood does not always correlate with intestinal levels. A test for faecal
IgA has now been developed, which more accurately reflects intestinal IgA
content. This test is still only available for research purposes, but may
become more readily available in the future to identify IgA-deficient dogs
that may be at increased risk for developing SIBO. Using this technique,
it has already been shown that IgA-deficient German shepherd dogs have
an increased incidence of persistent intestinal infections with enteropathogenic
E. coli (EPEC), which may play a role in the development of SIBO.
Signs
Primary SIBO occurs typically in young adult
dogs. The main clinical signs are chronic intermittent diarrhoea and weight
loss or failure to gain weight. Often, signs have been present since puppy
hood. Occasionally, weight loss is the only sign. Appetite may be variable
but is often decreased. Affected dogs frequently have a rough, dull hair
coat.
How to diagnose SIBO
A firm diagnosis of SIBO can be very difficult
to make, due to the lack of sensitive and specific tests. Initial tests
should eliminate other causes of diarrhoea and/or weight loss, such as
intestinal parasites and pathogens, systemic disease, intestinal obstruction
and EPI. Few indirect tests are then available to detect SIBO; measurement
of blood folate and cobalamin concentrations may help to diagnose clear-cut
cases and is easy to do in practice, but the test is not very sensitive
and normal results do not rule out SIBO. Definitive diagnosis of SIBO is
based on results of microbiologic culture of duodenal juice obtained during
endoscopy or surgery, demonstrating increased bacterial numbers. Obviously,
this is invasive, time-consuming and expensive, whereas duodenal juice
culture is a specialised technique that is only available in referral institutions.
However, establishing a firm diagnosis of SIBO is important especially
in dogs with severe and/or recurrent signs, since they may require long-term
treatment. In addition, intestinal biopsies can be taken at the time of
duodenal juice collection, so that other intestinal diseases can be ruled
out.
Because of the difficulties in diagnosing SIBO,
much research is being done to evaluate other tests. The hydrogen breath
test is relatively simple and may be helpful, but it has its limitations
and is at present available in only a few places. Further tests, such as
a blood test for unconjugated bile acids, are still in the early stages
of development.
Treatment of SIBO
Treatment of SIBO is much more likely to be successful
if an underlying cause can be identified and corrected. However, if a cause
cannot be identified, treatment with antibiotics such as oxytetracycline
is required, often for considerable periods of time. Many dogs respond
to short-term (4 weeks) antibiotic treatment but relapse when treatment
is stopped; they may then need to be treated for several months. During
long-term treatment, it may be possible to reduce antibiotic dosages without
causing a recurrence of clinical signs. The goal of antibiotic therapy
is therefore not to sterilise the gut but to modify the intestinal flora
and to encourage the establishment of less harmful bacteria. Some dogs
with chronic SIBO can be difficult to manage because of recurrent diarrhoea
despite appropriate antibiotic treatment. This seems to be particularly
the case in German shepherd dogs, possibly because of an underlying Immune-deficiency.
Failure to respond to antibiotics may furthermore be attributable to irreversible
damage to the intestinal mucosa caused by the bacteria, antibiotic resistance
and/or concurrent disease (for instance, inflammatory bowel disease).
Dietary management with a highly digestible,
low-fat diet is important in all dogs with SIBO in order to facilitate
adequate absorption of nutrients and minimize the consequences of bacterial
interaction with malabsorbed fat. Additional treatment with vitamin B12
is often also necessary since SIBO can result in a very low blood B12-level,
which has a negative effect on intestinal function. The diet may also be
manipulated to try to change the intestinal flora towards a more normal
composition. Some commercial diets now contain fructo-oligosaccharides
(FOS), which are naturally occurring plant sugars. They are not digestible
by the host and remain intact in the small intestine until they reach the
colon, where specific bacteria break them down. FOS-supplementation may
reduce the growth of potential pathogenic bacteria in the colon because
they are unable to ferment it, whereas it may induce the proliferation
of non-pathogenic, ‘good’ bacteria. There are only a few studies looking
at the effects of dietary FOS supplementation in the dog and cat, and they
do not indicate any great clinical efficacy. FOS supplementation has been
used in German shepherd dogs with SIBO in an attempt to reduce bacterial
numbers in the small intestine, but results have been rather dubious..
Probiotics are another potential therapeutic
tool. They are a mixture of one or more harmless bacteria, usually including
Lactobacilli, which are given by mouth hoping that they will colonize the
small bowel, thus displacing ‘unfavourable’ microorganisms. The use of
yogurt for this purpose is not recommended in dogs since this may diarrhoea
worse, whereas it is unlikely that the bacteria in yogurt are able to colonize
the dog gut. Studies in people suggest that probiotics can be helpful in
controlling enteric pathogens, but it is unknown whether they can do the
same for bacterial overgrowth.
Inflammatory bowel disease
What causes inflammatory bowel disease?
Inflammatory bowel disease is not a single disease
but a group of diseases characterised by infiltration of the intestinal
mucosa with inflammatory cells. The whole bowel may be affected, or only
parts of it. It can be divided into different subtypes based on the main
type of inflammatory cell present. The inflammation is in many cases just
a non-specific immunologic response to a variety of antigens in the bowel
lumen, such as parasites and bacterial pathogens, intestinal bacteria and
food antigens. In some cases, this response is excessive due to an abnormally
active immune system. Animals with a very permeable (leaky) gut may be
more prone to developing inflammatory bowel disease, because it makes it
easier for antigens to gain access to the intestinal wall.
German shepherd dogs appear to be predisposed
to developing inflammatory bowel disease as well as SIBO, and it seems
likely that at least in some cases there is an association between the
two. It may be that the inflammatory bowel disease reflects a dysregulated
intestinal immune response to the increased numbers of bacteria within
the intestine. Although the breed is predisposed to developing these two
diseases, there is at present no evidence that either is inherited.
Signs and diagnosis
Affected dogs usually have signs of vomiting
as well as diarrhoea and weight loss. There are no specific findings on
examination of faeces and blood, and diagnosis has to be made by pathologic
examination of intestinal biopsies, obtained either during endoscopy or
at surgery. When possible, known causes of intestinal inflammation should
be identified and eliminated, particularly parasites, bacterial pathogens
and food allergy. In order to exclude the latter, it is prudent to undertake
a dietary trial with a selected protein diet, containing a protein the
dog has not eaten recently, for a minimum of 3 weeks prior to considering
further investigation using biopsy. Dogs with food allergy generally improve
on such a diet but relapse when challenged with the original, offending
food.
Treatment
Dietary therapy in inflammatory bowel disease
is aimed at facilitating absorption of food and at reducing antigenic challenge
to the gut. The diet should be highly digestible and contain one or few
selected protein sources that the dog has not been exposed to recently.
Other potential causes of intestinal inflammation, such as parasites and
infections, should also be identified and treated if possible, and in some
cases this may be enough to prevent the need for further therapy. Dogs
with severe inflammatory bowel disease, however, will require additional
treatment with immune-suppressive drugs, such as corticosteroids. Treatment
may last weeks to months.
The role of diet in managing canine inflammatory
bowel disease is likely to become more important in the future. There is
increasing evidence that dietary factors, for example anti-oxidants, can
be important to reduce the heightened intestinal immune response and decrease
inflammation.
FUTURE CONSIDERATIONS
Where do we go from here? There is much to be
learned about intestinal disease in the dog and particularly why German
shepherd dogs are so predisposed to developing the above diseases. Probably
the ‘hottest’ area is that of small intestinal bacterial overgrowth, with
emphasis being placed on improving methods of detection and treatment.
Will blood tests and/or breath tests be able to replace duodenal juice
culture in the diagnosis of SIBO, and will we find a treatment alternative
to prolonged antibiotic therapy? Will we be able to identify and correct
IgA-deficiency before it results in clinical signs? Will we be able to
diagnose and treat EPI before it is irreversible and needs indefinite enzyme
supplementation? And finally, can further dietary modification give diet
a greater role in the treatment of intestinal disease? There are still
many questions, but the current rate of progress in biomedical science
should considerably speed our progress to the answers.
Causes of chronic diarrhoea in the dog
? Dietary sensitivity
? Parasites (worms, Giardia)
? Intestinal infections (mostly bacterial)
? Exocrine pancreatic insufficiency (EPI)*
? Small intestinal bacterial overgrowth*
? Inflammatory bowel disease*
? Other intestinal diseases (e.g. lymphangiectasia,
tumours, obstructions)
? Systemic disease (e.g. liver, kidney, hormonal)
* Intestinal disorders to which German shepherd
dogs are predisposed
Tests for chronic diarrhoea in the dog
Baseline investigation
1. Stool examination (parasites, culture)
2. Routine blood tests (haematology, biochemistries)
3. (Optional: X-rays, ultrasound)
Investigation of EPI
4. Blood test for TLI determination
Assessment of small intestinal disease
5. Blood tests for serum folate and cobalamin
6. Response to dietary trial with selected protein
diet
7. Intestinal biopsy (via endoscopy or surgical)