Canine enteropathy is often used to describe chronic gastrointestinal signs in dogs (Dandrieux, 2016); the clinical signs characterising canine enteropathy are vomiting, diarrhoea, borborygmus, hyporexia and weight loss (Dandrieux, 2016). There is no single test available to diagnose canine enteropathy. Multiple diseases such as adverse food reactions, idiopathic inflammatory bowel disease (IBD) and antibiotic-responsive diarrhoea present with clinical signs affecting the intestinal tract. History taking and a thorough clinical examination using the Canine Chronic Enteropathy Disease Activity Index (Mandigers and German, 2010) is essential when treating any patient. Patients with gastrointestinal signs could undergo endoscopy; it would not diagnose the cause of the enteropathy, merely confirm its presence. In both adverse food reactions and IBD, biopsies taken using endoscopy show villous atrophy, infiltration of lymph, plasma and eosinophils, and an abnormal intraepithelial lymphocyte infiltration (Mandigers and German, 2010). Therefore, once extra-intestinal, parasitic disease (Dandrieux, 2016) or bacteriosis is ruled out, these disorders are commonly diagnosed retrospectively by their response to treatment (Allenspach et al, 2007); the use of hydrolysed diets as a primary treatment can aid in the diagnosis by distinguishing between idiopathic enteropathies and adverse food reactions.
The author performed a literature search using two scientific databases, CAB Abstracts and MedLine as well as Google Scholar.
The use of diets to treat adverse food reactions
Patients that develop enteropathies as a reaction to a food allergen have commonly been exposed to a variety of proteins when fed a commercial maintenance diet; this number increases when the patient is also offered scraps (Mandigers et al, 2010). Therefore, the variety of formulations of protein exclusion diets available to each patient is significantly diminished; many would still contain a protein the patient has already been sensitised to (Mandigers et al, 2010). If it is found the patient does not react to a novel protein diet, there is the risk the animal will also become sensitised to that protein. Moreover, if the patient was fed a diet that is completely lacking in all proteins they will develop a protein deficiency, subsequently resulting in a multitude of health problems. A solution to this is a hydrolysed diet, where the proteins undergo enzymatic hydrolysis (Cave, 2006); a chemical reaction using enzymes to break down the proteins into smaller structures. This enables the prevention of immune recognition by patients that have already been sensitised to the intact protein by removing any allergens or allergenic epitopes, as these become immunologically inactive should the cleavage be within an antigenic peptide sequence (Cave, 2006).
Although diets containing hydrolysates as a protein source (Figure 1) have only been available for a short period of time in the veterinary world, studies have successfully proven that clinical gastrointestinal signs have been resolved with their use. In a dietary trial to investigate the effects of a commercial chicken hydrolysate diet in 63 pruritic dogs, Loeffler et al (2004) discovered that nine of the dogs had an adverse food reaction and six of those dogs had gastrointestinal signs which resolved on the trial diet, but recurred when their original diet was resumed. Furthermore, this trial proved hydrolysed diets could also treat concurrent enteropathy that was not a direct result of an adverse food reaction. 21 of the dogs had originally presented with concurrent gastrointestinal signs; in 19 of the dogs the gastrointestinal signs were completely resolved after completion of the clinical trial, and in two dogs the diarrhoea had improved to soft, formed faeces (Loeffler et al, 2004). However, the lack of a comparable control in this study raises questions over its validity.
A further retrospective study was undertaken to compare the chicken hydrolysate diet to home prepared diets. A larger number of subjects (n=181) were involved; 72 dogs were fed home prepared diets and 109 were fed the chicken hydrolysate diet (Loeffler et al, 2006). Out of all those participating in the trial, 36 dogs showed gastrointestinal signs which resolved in 24 dogs when fed either diet, and recurred on dietary provocation (Loeffler et al, 2006). This trial supports the original by Loeffler et al (2004), suggesting the method is reliable and that this specific commercial hydrolysate diet is just as useful as home prepared diets in diagnosing canine adverse food reactions with gastrointestinal signs (Loeffler et al, 2006). The primary aim of both these studies was to assess whether a hydrolysed diet can successfully treat pruritus; it has not been proven whether the improvement of gastrointestinal signs was due to the high digestibility of the diet or as a result of the pruritus resolving (Loeffler et al, 2004).
Hydrolysed diets and idiopathic canine enteropathy
Dogs that respond to an elimination trial but do not subsequently relapse when challenged with their original diet do not have a true adverse food reaction, instead enteritis, enterocolitis or colitis is more likely (Gaschen and Merchant, 2011). Hydrolysed diets can be used to treat enteropathies, such as IBD, where adverse food reactions are not the cause because sensitisation within the initial treatment phase is less likely than when a novel protein diet is used (Cave, 2006). These diets have been available for nearly two decades, yet there is minimal evidence on their role in diagnosing and treating enteropathy when adverse food reactions are not the primary cause. This is due to a lack of trials investigating the efficacy of diets formulated for dogs using hydrolysates as the amino acid source (Cave, 2006). As a result, experience and knowledge in the veterinary community is still rudimentary (Cave, 2006) with the diets only used in a trial and error manner alongside other treatment.
A study specific to canines with idiopathic canine enteropathy was undertaken in which dogs were fed either a test diet of hydrolysed soy and chicken (n=18), or an intestinal diet (n=8) as a control (Mandigers et al, 2010). The first evaluation of the trial showed a response rate of 88% (Simpson and Jergens, 2011), with gastrointestinal signs improving in both the test group and the control group. Following the 3-year trial period however, 13 of the test dogs on the hydrolysed diet remained in remission whereas only one out of the six remaining control diet dogs were asymptomatic (Mandigers et al, 2010). This was a randomised trial ensuring there was no bias in choosing which diet each dog was given, however both the veterinary surgeon and the owner were aware of which diet the patient was being fed so bias could have been introduced unintentionally. To improve the validity of the study a double-blind method would have been more suitable as Mandigers et al (2010) suggest in their discussion, and a cross-over design could potentially be used simultaneously (Marks et al, 2001). The number of subjects enrolled in this study was minimal, suggesting that the method of encouraging owner compliance needs improvement; owners' reluctance to return for multiple follow-up checks or challenge their pet with the original diet has been noted to be a common reason for a cease in participation (Marks et al, 2001; Mandigers et al, 2010).
The only case study with an acceptable number of participants, specific to dogs with canine chronic idiopathic large bowel diarrhoea (CILBD), discovered that 37 dogs successfully responded to a highly digestible diet with added psyllium (Lecoindre and Gaschen, 2011). A hydrolysed diet was not used in this study though they are known to provide a good source of highly digestible protein (Dossin and Lavoué, 2011). It has been shown that small peptides are more easily absorbed than amino acids (Cave, 2006) suggesting that they could be used to treat CILBD provided the diet also has a high fibre content. A study of six dogs presenting with CILBD supports this; four dogs recovered without extra treatment on a hydrolysed diet alone, and two recovered with extra treatment to treat concurrent exocrine pancreatic insufficiency (Dog 5) and lymphoplasmytic gastritis (Dog 3) (Marks et al, 2001). Although the patients had received other combinations of treatment at their referring veterinary practices, the study itself did not use a control group or compare the test diet against other forms of treatment which can be highlighted as a weakness. It also contained a small number of participants which could not provide a firm conclusion, and all dogs were of a different breed. Marks et al (2001) commented in their discussion that the owners were not blind to the test diet which could have caused bias.
Evidence against hydrolysed diets
Although the antigenicity of the protein in hydrolysed diets is significantly reduced, the risk of promoting an immunemediated response is not completely abolished; enzymatic hydrolysis can expose previously hidden antigenic sites, potentially causing an increase in antigenicity (German et al, 2003; Cave and Guildford, 2004). Commercial hydrolysed diets still have the potential to contain molecules 10 kDa or greater, which are large enough to initiate type one hypersensitivity reactions by the cross linking of two or more IgE molecules (Cave and Guildford, 2004). Jackson et al (2003) discovered that 21% of dogs reacted adversely to a hydrolysed soy protein diet after being challenged with soy and corn with a peak response 14 days post challenge. It has been reported by Cave (2006) that as the number of human hydrolysed diets increases, the number of hypersensitivity reactions including anaphylaxis also increase, suggesting that patients should be fed a diet with a protein they have not been previously exposed to as a precaution, even if the diet is hydrolysed. This can be just as difficult in veterinary medicine as finding a novel protein diet, especially if the patient has been fed scraps from the table. The use of extensively hydrolysed formulae has shown reduced growth, decreased serum albumin, and increased serum urea in newborn infants due to reduced nitrogen use (Cave, 2006), however this has not yet proven to be a problem with the use of commercial veterinary diets as they only undergo moderate hydrolysis.
Test diets in various studies differ widely in their protein composition, yet are made up from few ingredients, suggesting that instead of the protein modification, it may be the absence of specific ingredients which may have a beneficial effect (Simpson and Jergens, 2011). Other nutritional variables could also affect clinical responses, such as the correction of vitamin or mineral deficiencies or a lowered ω (n)-6/n-3 fatty acid ratio (Cave, 2006). Studies to investigate the efficacy of hydrolysates alone should use two diets identical in composition except with one group of participants using the hydrolysed form of the protein, and the other using the whole form (Cave, 2006). It is also not yet known whether a lower protein content can decrease antigenic load and therefore provide clinical benefit (Mandigers et al, 2010); this could provide a cheaper alternative than protein hydrolysis should further studies be undertaken.
Discussion
The literature available regarding the use of hydrolysed diets to treat canine enteropathy was minimal, the majority of studies focused on treating pruritus and cutaneous adverse food reactions. However, all studies concurred that the dogs presenting with gastrointestinal signs recovered when fed the test hydrolysed diet. Generally, the studies were funded by corporations producing the diets including Mars (Royal Canin) and Nestlé (Purina). They contained small numbers of participants, many lacked a control diet and those that did fed the diets via an open label method; the validity of these studies may be questioned, however they all concluded that hydrolysed diets can be used to treat various causes of canine enteropathy, usually without the need for other medication. Although it has been proven that the diets treat canine enteropathy compared with home prepared and normal diets, further research needs to be undertaken to assess the comparative efficacy of diets that contain a protein hydrolysate and novel protein diets.
After critically evaluating the literature, the author believes that hydrolysed diets can play a major role in treating canine enteropathy; their use can help veterinary surgeons to retrospectively diagnose the cause of the disease by allowing the patient to enter a remission phase where it can then be challenged with specific food antigens in a cost effective and non-invasive manner, an attractive prospect for the client. Reflecting on her own experience in the veterinary practice, the author feels these diets are an ideal primary treatment for patients with enteropathies, including allergies, food intolerance and IBD, for minimising stress to both the client and the patient, and are more favourable than novel protein diets due to the reduced risk of a further reaction to the diet. The role of the veterinary nurse is paramount in supporting clients who may be unsure about the use of a diet as a treatment. A nurse clinic to explain the differences between normal diets, novel protein diets and hydrolysed diets as well as provide help with choosing and locating the best hydrolysed diet for the patient may help the client feel less overwhelmed and increase compliance.