Pro-Bio+ Technical Bulletin
Pro-Bio+ is a nutritional supplement that provides digestive support to dogs, cat, puppies and kittens with diarrhoea or digestive disturbances
Diarrhoea and digestive disturbances are among the most frequent reasons that dogs and cats are presented to vets. While distressing for the pet owner to witness, diarrhoea/vomiting and digestive disturbances can result in impaired absorption of nutrients and in the long term, significant debilitation in animals.
The most common causes of diarrhoea and digestive disturbance are dietary indiscretion, changes in diet, and infectious causes (Hall, 2005). Less commonly acute diarrhoea can be caused by chemotherapeutic agents and adverse drug reactions. Animals that experience diarrhoea often become depressed, anorexic and dehydrated. Malabsorption/maldigestion conditions such inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO) and exocrine pancreatitic insufficiency (EPI), for example, can result in chronic diarrhoea. Acute and chronic pancreatitis are painful causes of vomiting and diarrhoea in both dogs and cats and is associated with marked pancreatitic inflammation, autolysis of pancreatitic tissues and in severe cases death. Long standing cases of chronic pancreatitis can result in EPI. Irrespective of the cause of diarrhoea, and as a result of gastrointestinal inflammation and/or rapid transit of gastrointestinal contents, absorption of nutrients, including vitamins, can be compromised. This is especially important with vitamins, many of which are passively absorbed by the small intestine and subnormal concentrations of serum cobalamin have been reported in cats with gastrointestinal disease (Simpson, 2001). In addition antibiotic therapy (such as that used in SIBO) lead to profound changes in the intestinal microflora (Grønvold, 2010) which are necessary for the production of vitamin K2, the water soluble B vitamins, biotin and folate (Suchodolski, 2011).
Irrespective of the cause of the digestive disturbance, supportive treatment including nutrition supplementation is important.
The aims of nutritional supplementation are to:
- Replace fluid losses through rehydration, including where necessary intravenous fluids
- Replace protein, carbohydrate and fat losses by encouraging return to normal appetite
- Replace vitamin losses
- Restore normal intestinal motility
- Promote gastrointestinal and systemic immunity
- Limit fluid losses and protect gastrointestinal mucosa from further damage
- Stabilise and replace intestinal microflora
- While some nutritional supplements address some of the above aims, few address the need to supplement vitamins, especially B vitamins.
Pro-Bio+ is formulated to address the needs of dogs and cats with digestive disturbance and diarrhoea, through the provision of the following supplements:
Kaolin has stood the test of time as a supportive treatment for diarrhoea. It works by absorbing excessive fluids in the gastrointestinal tract, providing a protective layer on the mucosal surface and by absorbing bacterial enterotoxins and endotoxins (Hall, 2005, Wilke, 1987).
Probiotic; Enterococcus faecium (NCIMB 10415, E1707 3X1011cfu)
Commensal gut microbes, Enterococcus faecium being one of many, play a crucial role in host health. They act as a defending barrier against invading pathogens, aid in digestion and energy harvest from the diet, provide nutritional support for enterocytes and stimulate the development of the immune system. In addition, the short chain fatty acids produced by microflora metabolism, promote normal gastrointestinal motility (Kamath, 1987). Alterations in the composition of the intestinal microbioflora have been implicated with to chronic enteropathies in dogs and cats (German et al., 2003). The presence of intestinal bacteria in early life is necessary to establish oral tolerance to commensal bacteria and food antigens, to prevent onset of an inappropriate immune response, which may lead to chronic gastrointestinal inflammation (Bauer et al., 2006). Microbes interact and stimulate the immune host system, as has been shown by administration of specific bacterial strains as probiotics in dogs and cats. Important changes in the intestinal microflora occur at weaning and when changing diet and supplementation of food with Enterococcus faecium (NCIMB 10415, SF68) has been demonstrated to stimulate immune function in young dogs, at the mucosal and systemic levels (Benyacoub, 2003). Administration of Enterococcus faecium to cats in animal shelters significantly reduced the number of cats experiencing diarrhoea of two days or more duration (Bybee, 2011).
α-tocopherol – (vitamin E)
α-tocopherol is an essential vitamin and the α – form is the most active saturated form of Vitamin E available. Digestion occurs in the small intestine and is related to fat digestion and requires bile and pancreatic lipase. α-tocopherol has long been established as the biological anti-oxidant, by virtue of its ability to stabilise cell membranes and reduce the production of free radicals. Normal dogs and cats experience oxidative damage and increased dietary levels of antioxidants may decrease in vivo measures of oxidative damage (Jewell, 2000). In addition, α-tocopherol protects against DNA damage to cells and cause ageing (Heaton, 2001) and α-tocopherol promotes disease resistance through its ability to stimulate antibody production, T-helper 1 cell cytokine production (Han, 2000), and to promote phayocytosis (Meydani, 1996). Vitamin E is believed to be especially important in young puppies and kittens with developing immune systems (Hayek, 2000). More recently α-tocopherol has been demonstrated to have a reduction in inflammatory joint markers and an improvement in pain in dogs with a surgically induced early osteoarthritis (Rhouma, 2013). Interestingly, a combined meta-analysis of chronic pancreatitis in humans has shown that a combination of anti-oxidants, including vitamin E, was associated with pain relief (Cai, 2013).
Ascorbic acid (Vitamin C)
Ascorbic acid is the vitamin typically associated with scurvy, most dogs and cats. During times of stress (e.g. dietary, performance, management, temperature, disease) or high production, ascorbic acid synthesis decreases in dogs and cats. Ascorbic acid plays an important anti-oxidant role in combination with other vitamins, such as vitamin E (Heaton, 2001). Ascorbic acid plays an important role in immunity and has been demonstrated that supplementation of diets with ascorbic acid in combination with α-tocopherol in healthy and aged beagles resulted in significantly enhanced neutrophil phagocytosis (Hall, 2011). Ascorbic acid is also essential for the formation and maintenance of collagen important components of skin, connective tissue, cartilage, muscle, bone and teeth (Holmannová, 2012). There are various forms of ascorbic acid however L-ascorbic acid – E300 is the purest form (99% purity).
The B Vitamins
Thiamine (Vitamin B1)
Thiamine is an essential vitamin. All animals require thiamine, and it is synthesised by bacteria, yeast and plants therefore animals must obtain thiamine from their diet. Deficiencies in thiamine are characterised by anorexia, weakness and malaise. Any disruption to an animal’s commensal flora, could alter thiamine production. Thiamine deficiency associated with SIBO has been reported in humans (Lakhani, 2008). Additionally thiamine is water soluble and susceptible to destruction by heat, neutral and alkaline conditions, oxidising and reducing agents and ionizing radiation. Thiamine is a coenzyme in the conversion of carbohydrates to provide energy, it is essential for Krebs cycle within cells, plays a role in insulin biosynthesis, and is vital in nerve function (through its role in acetylcholine synthesis and thus smooth muscle function) and maintenance of the myelin sheath. Consequently it is necessary for peristaltic activity of the stomach and intestines (Jankowska-Kulawy, 2010) and to maintain normal gut motility and appetite. It has recently been reported that humans infected with enterotoxigenic E. coli infection can suffer thiamine deficiency (Ghosal, 2013). Thiamine deficiency has also been reported in humans that have undergone extensive bariatric surgery (Mrsić, 2012).
Riboflavin – (Vitamin B2)
Riboflavin promotes growth, food conversion, fertility and improves skin and coat condition. It is believed to be a component of the retinal pigment of the eye and contributes to improved eye sight. Riboflavin is an essential component of co-factors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which is required for the metabolism of carbohydrates, proteins, nucleic acids and fats and has an essential role in several oxidation processes (Charlton, 2007). Riboflavin is essential for maintaining the integrity of mucous membranes, the epithelial barrier and nerve fibre integrity. Additionally riboflavin is required for the activation of pyridoxine (vitamin B6) for its role in the formation of niacin from tryptophan. Protein bound riboflavin is released during digestion, and its absorption occurs in the small intestine by passive diffusion. Generally it is not well absorbed, and it has been reported that the riboflavin requirements of adult dogs are greater than previously thought (Cline, 1996). Increased gastrointestinal transit associated with diarrhoea, could reduce riboflavin absorption. Riboflavin is believed to be required for adrenal gland function and hormone production (Mookerjea, 1962; Forker, 1955).
Pyridoxine Hydrochloride (Vitamin B6)
Pyridoxine is an essential vitamin involved in many metabolic processes; it plays a key role in energy production, central nervous system activity as well as the blood and immune systems. It is synthesised in the intestine by microorganisms and large losses occur in feed processing. Pyridoxine is essential for DNA and RNA synthesis and is involved in the synthesis, transport and breakdown of amino acids (Rosenberg, 2012). More than 60 enzymes rely on pyridoxine coenzymes. Pyridoxine is involved in haemoglobin and red blood cell formation, in the synthesis of antibodies and in inflammation (involved in the conversion of linoleic acid to arachadonic acid). It is critical for the production and synthesis of numerous body chemicals, including insulin, neurotransmitters, enzymes, prostaglandins, histamine, dopamine, and adrenaline and it is also involved in the synthesis of niacin from tryptophan and in carbohydrate metabolism. Pyridoxine is rapidly absorbed from the small intestine. Requirements vary depending on age, physiological stress, intestinal microflora (Kore, 2010), environmental temperature and dietary components.
Cyanocobalamin – Vitamin B12
Cobalamin is the largest and most complex of all the vitamins. It is essential in all the basic metabolic functions including protein, carbohydrate and fat metabolism. Additionally it is an essential part of many enzymatic processes and is a key vitamin in the prevention of anaemia. Absorption occurs slowly in the small intestine and has low efficiency (1% absorbed). There is reduced absorption in cases of small intestine bacterial over growth (SIBO). Hypocobalaemia, has been a risk factor associated with a negative outcome in dogs suffering from chronic enteropathies (Allenspach, 2007)
Menadione 500mg (vitamin K3)
Menadione is a pro-vitamin and precursor to vitamin K. Vitamin K is essential in the blood clotting process and depletion of vitamin K reserves can occur in cases of chronic low grade haemorrhage. Many dogs and cats with chronic intestinal disease or parasitism have pre-existing anaemia. Recent reports in the human literature suggest that menadione may have a supportive role in the treatment of cancer (Osada, 2008).
Calcium-D-Pantothenate 6,000mg (Vitamin B5)
Calcium pantothenate is an essential vitamin required for the synthesis of co-enzyme A (CoA) and to synthesise and metabolise proteins, carbohydrates and fats. It is also required in the synthesis of acetylcholine. Consequently it plays an essential role in metabolism and energy levels. As with other water soluble B vitamins it is absorbed from the small intestine via specific carrier systems synthesised by intestinal microflora (Said, 2011). Any disruption to the microflora can impair absorption.
Nicotinic Acid 5,000mg (vitamin B3)
Nicotinic acid is produced from tryptophan and is a precursor of NAD and NADP which are co-enzymes required by many dehydrogenases. NAD is important in catabolism of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP mostly in anabolism reactions such as fatty acid and cholesterol synthesis. High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency. Nicotinic acid is also important in gastrointestinal motility. Feline species, including the domestic cat, evolved as strict carnivores. As such, their nutritional idiosyncrasies are legendary including an inability to effectively convert tryptophan to niacin, as a result of the high activity of enzymes that metabolise the precursors of this vitamin to other compounds. Consequently, while meat is well supplied with the NAD and NADP coenzymes, and while cats consume a diet of animal tissue there is no need to produce niacin from tryptophan. Anorexic cats may not receive sufficient supplies of niacin from meat sources (Morris, 2002, Baker, 2008)
There are many supplements in the veterinary market that claim to provide nutritional support to dogs and cats suffering from gastrointestinal disturbances. Most contain gastrointestinal adsorbents and/or protectants, some contain probiotics to support and replace the impaired gastrointestinal flora, but few contain the range of vitamins, especially vitamins A and E and the B vitamins necessary to promote immunity, enhance appetite and gastrointestinal motility and support repair of the gastrointestinal system. Pro-Bio + offers kaolin, Enterococcus faecium and a range of vitamins to promote digestive health.
Baker. D.H. Animal Models in Nutrition Research1 J. Nutr. (2008)138: 391–396
Bauer, E., B. A. Williams, H. Smidt, M. W. Verstegen, and R. Mosenthin. Influence of the gastrointestinal microbiota of dogs and cats on development of the immune system in young animals. Curr.Issues Intest. Microbiol. (2006) 7:35–51.
Benyacoub, J., Czarnecki-Maulden, G. L., Cavadini, C., Sauthier, T.Anderson, R.E., Eduardo J., Schiffrin, E.J. and Thierry von der Weid, T. Supplementation of Food with Enterococcus faecium (SF68) Stimulates Immune Functions in Young Dogs. J. Nutr. (2003) 133: 1158–1162
Bybee, S.N., Scorza, A.V. and Lappin M.R. Effect of the Probiotic Enterococcus faecium SF68 on Presence of Diarrhea in Cats and Dogs Housed in an Animal Shelter Journal of Veterinary Internal Medicine (July/August 2011) Volume 25, Issue 4, pages 856–860
Cai, G-H., Huang, J., Zhao, Y., Chen, J., Wu, H-H., Dong, Y-L., Smith, H., Li, Y-Q., Wang, W. and Wu, S.X. Antioxidant Therapy for Pain Relief in Patients with Chronic Pancreatitis: Systematic Review and Meta-analysis. Pain Physician 2013; 16:521-532
Charlton, S.J. and Ewing W.N. The Vitamins directory, 2nd ed published by Context, 2007
Cline, J., Odle, J. and Easter. The riboflavin requirement of adult dogs at maintenance is greater than previous estimates. J. Nutr. April 1, (1996) vol. 126 no. 4 984-988
Forker, B. R and Morgan, A. F. Causes of pituitary-adrenal failure in the riboflavin deficient rat. J. Biol. Chem. (1955), 217:659-668.
German, A. J., M. J. Day, C. G. Ruaux, J. M. Steiner, D. A. Williams, and E. J. Hall. Comparison of direct and indirect tests for small intestinal bacterial overgrowth and antibiotic responsive diarrhea in dogs. J. Vet. Intern. Med.(2003) 17:33–43.
Ghosal, A., Chatterjee, N., S, Chou, T. and Said, H.M. Enterotoxigenic Escherichia coli infection and intestinal thiamin uptake: studies with intestinal epithelial Caco-2 monolayers. Am J Physiol Cell Physiol. (Dec 2013) 305(11):C1185-91
Hall, J.A., Chinn, R.M., Vorachek, W.R., Gorman, M.E., Greitl, J.L., Joshi, D.K. and Jewell DE. Influence of dietary antioxidants and fatty acids on neutrophil mediated bacterial killing and gene expression in healthy Beagles. Vet Immunol Immunopathol. 2011 Feb 15; 139(2-4):217-28.
Han, S,N., Wu, D., Ha, W.K., Beharka, A., Smith, D.E., Bender, B. S., and Meydani, S. N. Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with infuenza virus. Immunology (2000) 100 487-493.
Hayek, M.G., et al. Dietary vitamin E improves immune function in cats. In: Reinhart GA, Carey DP eds. Recent Advances in Canine and Feline Nutrition, Vol III: 2000 Iams Nutrition Symposium Proceedings. Wilmington, OH: Orange Frazer Press, 2000; 555-564
Heaton, P.R., Reed, C.F., Mann, S.J., Ransley, R., Joy Stevenson, J, Charlton, C.J., Smith, B.H.E, Harper, E.J. and Rawlings, J.M. Role of Dietary Antioxidants to Protect against DNA Damage in Adult Dogs. Presented as part of the Waltham International Symposium: Pet Nutrition Coming of Age held in Vancouver, Canada, August 6–7, 2001.
Jankowska-Kulawy A, Bielarczyk H, Pawełczyk T, Wróblewska M, Szutowicz A. Acetyl-CoA and acetylcholine metabolism in nerve terminal compartment of thiamine deficient rat brain. J Neurochem. (Oct 2010) 115(2):333-42.
Kamath, P. S., M. T. Hoepfner, and S. F. Phillips. Short chain fatty acids stimulate motility of the canine ileum. Am. J.Physiol. (1987) 253:G427–G433.
Lakhani SV, Shah HN, Alexander K, Finelli FC, Kirkpatrick JR, Koch TR. Small intestinal bacterial overgrowth and thiamine deficiency after Roux-en-Y gastric bypass surgery in obese patients. Nutr Res. 2008 May; 28(5):293-8.
Marks, S.L. Diagnostic and therapeutic approach to cats with chronic diarrhoea. Journal of Feline Medicine and Surgery, (June 2000); vol. 2, 2: pp. 105-109
Meydani, S.N. and Beharke, A.A. Recent Developments in Vitamin E and Immune Response. Nutrition Reviews 1996 Vol 56, No 1 p 49-58.
Mookerjea, S.C.J.S Possible effects of riboflavin deficiency on adrenal cortical function in rats Canadian Journal of Biochemistry and Physiology, 1962, 40(8): 1059-1064.
Morris JG. Idiosyncratic nutrient requirements of cats appear to be diet-induced evolutionary adaptations. Nutr Res Rev. 2002 Jun; 15(1):153-68
Mrsić, V., Adam, V.N., Velnić, D., Matolić, M., Stojcić, E.G., Barić, M.[Wernicke’s encephalopathy as a complication of bariatric surgery.[Article in Croatian] Acta Med Croatica. 2012 Mar; 66(1):17-22.
National Research Council. Nutrient Requirements of Dogs and Cats. Washington, DC: The National Academies Press, 2006.
Osada, S., Tomita, H., Tanaka, Y., Tokuyama, Y., Tanaka, H., Sakashita, F. and Takahashi, T. The Utility of Vitamin K3 (Menadione) against Pancreatic Cancer ANTICANCER RESEARCH (2008) 28: 45-50
Rhouma, M., de Oliveira El Warrak, A., Troncy, E., Beaudry, F. and Chorfi. Y. Anti-inflammatory response of dietary vitamin E and its effects on pain and joint structures during early stages of surgically induced osteoarthritis in dogs. The Canadian Journal of Veterinary Research 2013; 77:191–198