The role of Probiotics in Management of Acute Non ... - equistro.dk
The role of Probiotics in Management of Acute Non ... - equistro.dk
The role of Probiotics in Management of Acute Non ... - equistro.dk
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<strong>The</strong> <strong>role</strong> <strong>of</strong> <strong>Probiotics</strong> <strong>in</strong> <strong>Management</strong> <strong>of</strong> <strong>Acute</strong> <strong>Non</strong>-specific Diarrhoea<br />
GI disorders are one <strong>of</strong> the most common reasons a dog is brought to the vet.<br />
With cl<strong>in</strong>ical signs rang<strong>in</strong>g from diarrhoea, vomit<strong>in</strong>g, abdom<strong>in</strong>al cramps, <strong>in</strong>appetance and weight loss, it<br />
can be as distress<strong>in</strong>g for the owner as it is for the dog.<br />
Healthy Gut - Function and Nutrition<br />
Not only is the gut the organ <strong>of</strong> digestion and absorption, it is also the largest immune organ <strong>in</strong> the body<br />
– be<strong>in</strong>g the po<strong>in</strong>t <strong>of</strong> entry for <strong>in</strong>fectious diseases and allergy sensitis<strong>in</strong>g prote<strong>in</strong>s. <strong>The</strong> health <strong>of</strong> the gut is<br />
therefore critical to the health <strong>of</strong> the dog <strong>in</strong> ma<strong>in</strong>ta<strong>in</strong><strong>in</strong>g a strong immune system.<br />
<strong>The</strong> gut is the only body tissue that uses both systemic and lum<strong>in</strong>al nutrition source <strong>of</strong> energy. 1<br />
<strong>The</strong> large <strong>in</strong>test<strong>in</strong>e mucosal cells rely primarily on short cha<strong>in</strong> fatty acids as their lum<strong>in</strong>al energy<br />
source. Butyrate is the major SCFA energy source for colonocytes enabl<strong>in</strong>g them to function effectively. 3<br />
Fibre is fermented <strong>in</strong>to SCFA by micr<strong>of</strong>lora resident <strong>in</strong> the gastro<strong>in</strong>test<strong>in</strong>al tract. 4<br />
<strong>The</strong> small <strong>in</strong>test<strong>in</strong>e utilises nutrients such as glutam<strong>in</strong>e and other am<strong>in</strong>o acids as energy sources for<br />
the enterocytes. As the enterocytes are replaced every 3-5 days, starv<strong>in</strong>g the gut for periods <strong>of</strong> time may<br />
have negative consequences on the <strong>in</strong>tegrity <strong>of</strong> the mucosal barrier and make the gut vulnerable. 2
<strong>The</strong> Micr<strong>of</strong>lora<br />
<strong>The</strong> normal gut conta<strong>in</strong>s micr<strong>of</strong>lora – trillions <strong>of</strong> beneficial bacteria (10 14 ) <strong>of</strong> 400 different species 5 –<br />
required to help activate the digestive process. <strong>The</strong>se micr<strong>of</strong>lora also play an active <strong>role</strong> <strong>in</strong> host defence<br />
whereby colonisation resistance affords protection aga<strong>in</strong>st pathogens. 6 <strong>The</strong>y form a symbiotic relationship<br />
with the host which also enhances the immune system.<br />
At birth the puppies gut is relatively sterile but becomes <strong>in</strong>oculated by different bacteria from its<br />
environment. <strong>The</strong>se bacteria are collectively known as the micr<strong>of</strong>lora. <strong>The</strong> micr<strong>of</strong>lora is made up <strong>of</strong><br />
beneficial and pathogenic bacteria, the pathogens be<strong>in</strong>g suppressed to low levels when the <strong>in</strong>test<strong>in</strong>e is<br />
healthy.<br />
<strong>The</strong> Disturbed Gut - Unpleasant Symptoms<br />
<strong>The</strong> symptoms <strong>of</strong> a disturbed gut – particularly an acute case – can be hard for dog owners to ignore,<br />
and frequently results <strong>in</strong> a visit to the vet. Diarrhoea and/or vomit<strong>in</strong>g are common signs, but the dog may<br />
also show other signs suggestive <strong>of</strong> GI tract disease. Behavioural changes may <strong>in</strong>dicate abdom<strong>in</strong>al<br />
cramps and tenderness, or there may be excessive gas production (flatulence and borborygmi), weight or<br />
failure to ga<strong>in</strong> weight, and frequently <strong>in</strong>appetance.<br />
Causes<br />
Disturbance to gut function can be <strong>in</strong>fluenced by a range <strong>of</strong> factors, all <strong>of</strong> which may affect the microbial<br />
balance <strong>in</strong> the GI tract, caus<strong>in</strong>g some degree <strong>of</strong> dysbiosis:<br />
Changes <strong>in</strong> diet<br />
Scaveng<strong>in</strong>g and/or dietary <strong>in</strong>discretion<br />
Gastro<strong>in</strong>test<strong>in</strong>al disease such as parasites<br />
Antibiotic or other drug therapy<br />
Stress – i.e. through travel, kennell<strong>in</strong>g, post-surgery or wean<strong>in</strong>g.<br />
In most acute cases <strong>in</strong> dogs, multiple mechanisms may contribute to the diarrhoea 7 :<br />
Passive secretion through osmosis. This is a common cause <strong>in</strong> diet changes, dietary <strong>in</strong>discretion<br />
or ‘garbage <strong>in</strong>toxication’<br />
Active secretion<br />
Increased permeability <strong>of</strong> mucosa<br />
Abnormal <strong>in</strong>test<strong>in</strong>al motility<br />
<strong>Management</strong> <strong>of</strong> acute diarrhoea<br />
<strong>The</strong> management <strong>of</strong> acute diarrhoea cases will vary between vets and cases, but it is generally accepted<br />
that we should consider the fundamentals <strong>of</strong> diarrhoea management when treat<strong>in</strong>g our cases. That is:<br />
ma<strong>in</strong>ta<strong>in</strong><strong>in</strong>g hydration; protect<strong>in</strong>g the mucosal <strong>in</strong>tegrity; stabilis<strong>in</strong>g gut micr<strong>of</strong>lora; and modify<strong>in</strong>g toxic<br />
effects.<br />
Five ma<strong>in</strong> areas <strong>of</strong> management are:<br />
1. Fluid therapy: <strong>The</strong> most beneficial & <strong>in</strong>deed life sav<strong>in</strong>g component <strong>of</strong> management for acute<br />
diarrhoea is fluid therapy. Intravenous fluid therapy and hospitalisation are <strong>in</strong>dicated if the animal<br />
is dehydrated or vomit<strong>in</strong>g significantly. Oral rehydration therapy can be implemented with fluids<br />
and/or electrolytes if the animal is able to dr<strong>in</strong>k.<br />
2. Dietary modification: Provide a diet that is highly digestible prote<strong>in</strong> and carbohydrate is<br />
appropriate for most acute <strong>in</strong>test<strong>in</strong>al diarrhoeas. A high biologically active prote<strong>in</strong> source is ideal<br />
to assist repair <strong>of</strong> damaged tissue and replace the natural turnover <strong>of</strong> the enterocytes. Diets low<br />
<strong>in</strong> fibre and moderate <strong>in</strong> fat to ensure it is highly digestible –maximis<strong>in</strong>g nutritional absorption<br />
and reduc<strong>in</strong>g stra<strong>in</strong> on the digestive system, while provid<strong>in</strong>g adequate energy. Short term dietary<br />
modification is recommended to be <strong>in</strong>troduced to the dog <strong>in</strong> small, frequent meals. 8
3. Antibiotics and other Prescription only medication (POM): Historically antibiotics have used <strong>in</strong> the<br />
treatment <strong>of</strong> diarrhoea. Evidence now shows that <strong>in</strong> the majority <strong>of</strong> cases they are not <strong>in</strong>dicated<br />
or beneficial <strong>in</strong> both human and veter<strong>in</strong>ary fields. <strong>The</strong> World Health Organisation (WHO)<br />
recommends antibiotics should not be used rout<strong>in</strong>ely, only be<strong>in</strong>g used for specific bacterial<br />
<strong>in</strong>fections, after appropriate identification. 9 Other POMs may be <strong>in</strong>dicated depend<strong>in</strong>g on the<br />
presentation <strong>of</strong> acute diarrhoea patient.<br />
4. Anti-diarrhoeals: Anti-diarrhoeals such as Kaol<strong>in</strong> and Pect<strong>in</strong> can be important <strong>in</strong> the management<br />
<strong>of</strong> acute diarrhoeas. Kaol<strong>in</strong> is a naturally occurr<strong>in</strong>g clay. It is recognised for its adsorbent abilities<br />
and acts as a natural b<strong>in</strong>d<strong>in</strong>g agent. It has recently been shown to decrease the bioavailability <strong>of</strong><br />
<strong>in</strong>test<strong>in</strong>al <strong>in</strong>sults 10 . Pect<strong>in</strong>, from the sk<strong>in</strong> <strong>of</strong> fruits, has a sooth<strong>in</strong>g affect on the gut and is<br />
considered to have anti <strong>in</strong>flammatory properties. 11 Together they have been used for many years<br />
as part <strong>of</strong> diarrhoea management.<br />
5. <strong>Probiotics</strong> & Prebiotics: <strong>Probiotics</strong> and Prebiotics together can be utilized to manipulate the<br />
micr<strong>of</strong>lora <strong>in</strong>to more favourable balance after gut disturbances and <strong>in</strong> the management <strong>of</strong> acute<br />
diarrhoea. <strong>The</strong> beneficial bacteria can become depleted dur<strong>in</strong>g GI disruption, compromis<strong>in</strong>g the<br />
ability <strong>of</strong> the gut to function effectively. <strong>Probiotics</strong> provide an <strong>in</strong>flux <strong>of</strong> beneficial bacteria to the<br />
unbalanced gut. We will consider these <strong>in</strong> more detail.<br />
<strong>Probiotics</strong> and Prebiotics<br />
<strong>Probiotics</strong> are described as: “A live microbial” “which beneficially affects the host animal by improv<strong>in</strong>g its<br />
<strong>in</strong>test<strong>in</strong>al microbial balance”. 12<br />
<strong>Probiotics</strong> exert their beneficial effects by 3 ma<strong>in</strong> mechanisms:<br />
<strong>The</strong> first mechanism is that <strong>of</strong> competitive exclusion. Competitive exclusion works by a process <strong>of</strong><br />
competition between the Probiotic and pathogenic bacteria for adhesion or colonisation sites on the<br />
gastro<strong>in</strong>test<strong>in</strong>al wall, and also by competition for nutrients with<strong>in</strong> the gut. 13<br />
<strong>The</strong> second mechanism is through the production <strong>of</strong> lactic acid by the Probiotic microorganisms. Lactic<br />
acid is produced as a means <strong>of</strong> optimis<strong>in</strong>g the immediate environment <strong>of</strong> the Probiotic bacteria. Lactic<br />
acid production encourages growth <strong>of</strong> lactic acid bacteria whilst <strong>in</strong>hibit<strong>in</strong>g the growth <strong>of</strong> pathogenic<br />
bacteria such as E. coli and Salmonella. Under stress conditions the animals gut becomes more alkal<strong>in</strong>e<br />
and more prone to illness as the gut conditions become more suitable for the growth <strong>of</strong> pathogenic<br />
bacteria. 14<br />
A third mechanism is to enhance and regulate the immune system. <strong>The</strong> immune system is stimulated by<br />
<strong>Probiotics</strong> <strong>in</strong> several ways. <strong>Probiotics</strong> have been shown to <strong>in</strong>crease cytok<strong>in</strong>e production; phagocytic<br />
activity <strong>of</strong> the <strong>in</strong>nate immune system; and antibody production via the adaptive immune system. 15,16<br />
Prebiotics are non-digestible food <strong>in</strong>gredients that provide a source <strong>of</strong> nutrition for the bacteria – can help<br />
<strong>in</strong>crease the growth and viability <strong>of</strong> the beneficial bacteria <strong>in</strong> the gut. 17 Prebiotics are the food source<br />
preferentially chosen by Lactobacillus and Bifidobacterium spp which reside <strong>in</strong> the distal small <strong>in</strong>test<strong>in</strong>e<br />
and the large <strong>in</strong>test<strong>in</strong>e. <strong>The</strong>y are fermented <strong>in</strong> the colon by the micr<strong>of</strong>lora <strong>in</strong>to SCFA which is known as<br />
the bifidogenic process. 18 Prebiotics need to have a low hygroscopicity, as water will affect the viability <strong>of</strong><br />
the <strong>Probiotics</strong>. 19 Provid<strong>in</strong>g dual source prebiotics will benefit good bacterial stra<strong>in</strong>s cover<strong>in</strong>g a larger area<br />
<strong>of</strong> gut.<br />
A synergistic effect has long been identified between Prebiotics and Probiotic microorganisms, more<br />
recently <strong>in</strong> dogs, suggest<strong>in</strong>g it is more beneficial to the gut health than <strong>Probiotics</strong> alone. 20 This is what is<br />
commonly referred to as a Synbiotic formulation.
Ideal <strong>Probiotics</strong> Features<br />
When consider<strong>in</strong>g the use <strong>of</strong> probiotics <strong>in</strong> companion animals with acute non-specific diarrhoea, one<br />
needs to identify the ideal features <strong>of</strong> probiotics and how to avoid use <strong>of</strong> <strong>in</strong>appropriate products.<br />
Unfortunately, there is currently poor regulation <strong>of</strong> probiotics <strong>in</strong> the veter<strong>in</strong>ary <strong>in</strong>dustry. This was<br />
identified <strong>in</strong> a recent study from Canada 21 and highlights the importance <strong>of</strong> identify<strong>in</strong>g a quality<br />
manufacturer for source <strong>of</strong> appropriate probiotics, capable <strong>of</strong> exert<strong>in</strong>g a beneficial effect <strong>in</strong> the species for<br />
which it is dispensed.<br />
1. <strong>Probiotics</strong> need to be safe, non-pathogenic and non-toxic microorganisms. In the EU, the only<br />
stra<strong>in</strong>s registered for use are Enterococcus faecium and Lactobacillus acidophilus. 22 <strong>The</strong>se stra<strong>in</strong>s<br />
themselves can vary and not all stra<strong>in</strong>s <strong>of</strong> E.faecium should be assumed are registered for use <strong>in</strong><br />
dogs <strong>in</strong> the EU. <strong>The</strong> NCIMB (National Collection <strong>of</strong> Industrial, Mar<strong>in</strong>e and food Bacteria) collection<br />
bank plays an important <strong>role</strong> <strong>in</strong> reta<strong>in</strong><strong>in</strong>g an orig<strong>in</strong>al source <strong>of</strong> the stored stra<strong>in</strong>s for culture. This<br />
ensures that there is no genetic drift <strong>of</strong> the stra<strong>in</strong> over time, so we can ensure it is always non-<br />
pathogenic & non-toxic.<br />
2. Colony form<strong>in</strong>g units (CFU) refer to the number <strong>of</strong> live, viable cells present. A product should<br />
conta<strong>in</strong> large numbers to have a beneficial effect. Studies <strong>in</strong> humans suggest a m<strong>in</strong>imum<br />
therapeutic dose <strong>of</strong> 1x10 8 CFU/ day to exert a beneficial effect. 23 Low levels <strong>of</strong> Probiotic bacteria<br />
(provid<strong>in</strong>g they are appropriate for the species) will do no harm but are unlikely to produce a<br />
beneficial effect. Quality products will ensure they meet label claim at the end <strong>of</strong> the shelf life <strong>of</strong><br />
the product.<br />
3. <strong>Probiotics</strong> should be capable <strong>of</strong> surviv<strong>in</strong>g low pH <strong>of</strong> stomach and bile acids. Microencapsulation <strong>of</strong><br />
the probiotics with cryoprotectants is recommended. This affords the probiotics an additional<br />
protection barrier dur<strong>in</strong>g the production process as well as additional protection from the<br />
stomach acid and bile. Probiotic stra<strong>in</strong>s should also be selected based on their ability to survive<br />
these conditions. Stra<strong>in</strong>s that have been approved for use <strong>in</strong> companion animals have been<br />
proven <strong>in</strong> studies to survive the stomach pH and bile as well as other attributes. 24<br />
Acid stability <strong>of</strong> microencapsulated Enterococcus faecium 10415 EC No.E1707 In vitro unbuffered<br />
growth for 2 hours contact time.<br />
When held at a pH <strong>of</strong> 2.0 and pH 1.5 for a 2 hour period there is no significant loss <strong>in</strong> viability / concentration <strong>of</strong><br />
the bacterial stra<strong>in</strong>. This <strong>in</strong> vitro study mimics the stomach acid conditions. <strong>The</strong> contact time is extreme – a two<br />
hour contact time period without any buffer<strong>in</strong>g effect <strong>of</strong> e.g. food or water, before plat<strong>in</strong>g out. 14
4. Lastly, the <strong>Probiotics</strong> should rema<strong>in</strong> stable for long periods under normal storage conditions. This<br />
may be facilitated by freeze-dry<strong>in</strong>g or similar dur<strong>in</strong>g the f<strong>in</strong>al stages <strong>of</strong> manufacture. This<br />
additional process helps give the <strong>Probiotics</strong> their 2 year shelf life seen <strong>in</strong> some <strong>of</strong> the quality<br />
products available to the veter<strong>in</strong>ary market. 19<br />
<strong>Probiotics</strong> <strong>in</strong> use<br />
It is excit<strong>in</strong>g to see much more research <strong>in</strong> recent years, <strong>in</strong>to <strong>Probiotics</strong> <strong>in</strong> companion animals, as the<br />
benefits have been seen <strong>in</strong> humans and food production animals.<br />
Strompfova <strong>in</strong> 2004 assessed various attributes <strong>of</strong> a good probiotic <strong>in</strong> the can<strong>in</strong>e. 24 Stra<strong>in</strong>s were evaluated<br />
for acid and bile tolerance; production <strong>of</strong> antimicrobial substances (bacterioc<strong>in</strong>s) directly aga<strong>in</strong>st other<br />
pathogenic bacterial stra<strong>in</strong>s; and capacity <strong>of</strong> adherence to the can<strong>in</strong>e <strong>in</strong>test<strong>in</strong>al mucous. Both the survival<br />
<strong>of</strong> the <strong>Probiotics</strong> <strong>in</strong> the GI tract and ability to attach to the mucous are important because <strong>Probiotics</strong> need<br />
to be viable and able to attach and colonise to exert their beneficial effect. This attachment ability varies<br />
between the Probiotic bacterial stra<strong>in</strong>s <strong>in</strong> the different host species. F<strong>in</strong>d<strong>in</strong>gs <strong>in</strong> the dog were favourable<br />
for particular stra<strong>in</strong>s <strong>of</strong> E. faecium.<br />
Other research by various authors has also shown that the adm<strong>in</strong>istration Enterococcus faecium reduces<br />
Clostridium spp. Staphlococcus & Pseudomonas <strong>in</strong> the can<strong>in</strong>e. 25,26<br />
Specific immune studies have looked supplement<strong>in</strong>g Probiotic E. Faecium and stimulation <strong>of</strong> immune<br />
function <strong>in</strong> dogs as well as immune response to Giardia <strong>in</strong>fection <strong>in</strong> mice. 27,28 Both yield excit<strong>in</strong>g<br />
<strong>in</strong>formation for cont<strong>in</strong>ued research <strong>in</strong> these areas.<br />
Key Po<strong>in</strong>ts <strong>of</strong> <strong>Probiotics</strong><br />
o <strong>The</strong> importance <strong>of</strong> normal <strong>in</strong>test<strong>in</strong>al micr<strong>of</strong>lora is paramount to the resistance <strong>of</strong> pathogenic<br />
microorganisms<br />
o Antibiotic therapy, stress and dietary changes can <strong>in</strong>duce a disturbance <strong>in</strong> the gut micr<strong>of</strong>lora<br />
o <strong>Probiotics</strong> can be beneficial <strong>in</strong> the prevention <strong>of</strong> significant dysbiosis and therapeutically to reestablish<br />
the micr<strong>of</strong>lora and help ma<strong>in</strong>ta<strong>in</strong> gut function<br />
o A quality source <strong>of</strong> appropriate probiotics and a thorough understand<strong>in</strong>g <strong>of</strong> how to evaluate the<br />
various products are important.<br />
Written by: Jane McNae BVSc, MACVSc (Surg), MRCVS. International Technical Manager for <strong>Probiotics</strong><br />
International Ltd.
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