DIGESTIVE HEALTH - 2021.greencrossvets-symposium

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DIGESTIVEHEALTHin dogs & cats2021 edition for professional reference only

The gastrointestinalmicrobiomeDid you know?Antibioticsare dispensedin 1 in 3veterinaryconsultsacross Australia,1 with antibioticassociated diarrhoea (AAD)frequently presenting as acomplication of use.2The canine and feline gastrointestinal (GI) tracts are home to anecosystem of commensal microorganisms which are essentialto their normal function. This diverse and highly complexcollection of microorganisms, including bacteria, yeast,protozoa, and viruses is known as the GI microbiome.8, 9, 10A healthy, balanced, and stable GI microbiome is of crucialimportance for overall health as it plays a vital role in a rangeof physiological processes:9, 11Maintaining gutepithelial healthDigestive disordersin dogs and catsDefence ment7,13GI microbiomeDigestive disorders are common in companion animalsand cause stress to both pet and owner.3 Any conditionthat reduces the digestion or absorption of food, or altersits transit through the digestive tract can be considereda digestive disorder.4 In practice, veterinarians are mostfrequently presented with cases of acute gastroenteritis,colitis, pancreatitis, exocrine pancreatic insufficiency andinflammatory bowel disease (IBD).4, 5The most common signs of digestive disorders are vomitingand diarrhoea, or soft stools.4 There are numerous causes ofdiarrhoea in dogs and cats, which include but are not limitedto: medications (especially antibiotics), dietary indiscretion,abrupt dietary changes, hypersensitivities, dietaryintolerances, parasites and infectious pathogens.6Clinical signs ofdigestive ghtlossChange inappetiteAbdominalpainBlood or mucousin faecesConstipationDiarrhoea orsoft stoolsVitamin K,B9 and B12synthesis12Skin healthLocal andsystemicimmunityMetabolismThe GI tract is the major defence system of the body as itcontains 70% of the body’s immune tissue.14 Consequently,the most important function of the GI microbiomeis protection against infection and colonizationby pathogenic bacteria.7 By creating a physiologicallyunfavourable environment involving the secretion ofantimicrobials and gut pH adjustments, in addition tocompeting for oxygen, nutrients and mucosal adhesion sites,the resident microbiota subdue pathogenic bacteria fromcolonising.7 Complex carbohydrates are transformed by theGI microbiome into short chain fatty acids (SCFA) which arevital for stimulating intestinal motility in the ileum, another keydefence mechanism against the invasion of pathogens.7, 15, 16Did you know?10xThe number of microorganisms and their geneticmaterial in the GI microbiome is comprised oftrillions of cells, approximately 10 times morethan the total number of cells in the host body.7, 16Similar to the human fingerprint, every dog andcat host their own unique and individual microbialprofile. No two microbiomes are the same.7Differences in composition, species richness andtotal numbers of microbiota occur along thelength of the GIT.7

Dysbiosis: An imbalancein the microbiomeWhat aboutmetronizadole?The balance between beneficial “good” and pathogenic“bad” bacteria in the GI microbiome of mature dogs andcats is remarkably stable, ensuring optimal health. However,its composition adjusts during the course of an animal’s lifein response to several factors such as age, genetics, diet,environment, stress, medications and disease, all of which impactthis normal balance.16, 17, 18 An imbalance of the GI microbiome isreferred to as intestinal dysbiosis and is characterised by a vastdecrease in the microbial diversity (number of unique bacterialspecies) from healthy counterparts.9, 18,19Metronidazole is a nitroimidazole antibiotic empiricallyprescribed for the treatment of acute and chronicdiarrhoea.22 Its mechanism of action may includeantiprotozoal and antimicrobial functions.12, 22 However,metronidazole induces significant changes to the GImicrobiota, with dysbiosis patterns that resemble thoseseen in chronic enteropathies. Given the lack of provenbenefits, most veterinary gastroenterologists would currentlyadvocate against the widespread usage of metronidazolein the treatment of acute diarrhoea in dogs, except in caseswith a very specific indication such as Giardiasis.22Profound alterations in the GI microbiome are found in acuteand chronic enteropathies in dogs and cats such as acutegastroenteritis, inflammatory bowel disease and cases involvingantibiotic therapy.20The effects of dysbiosis: I ncrease in pathogenic bacteria, leading to theoverproduction and translocation of bacterial toxins7 Inflammatory stimulation of the immune system16 Damage to mucosal receptors Competition for nutrients Increased intestinal permeability Reductions in anti-inflammatory metabolites e.g. SCFA9, 18BalancedmicrobiomeImbalancedmicrobiomeThe science behindprobiotics & prebioticsProbiotics are defined as ‘live’ microorganisms, that whenadministered in adequate amounts, confer a health benefiton the host.23 The use of probiotics is based on their abilityto aid in the re-establishment of a microbial-host balancein the digestive system following on from dysbiosis, thusalleviating the clinical signs of GI disorders, allergies, and otherconditions.6, 21, 24 Commonly used commercial probiotics maycontain either a single species or a combination of Lactobacilli,Bifidobacterium and Enterococci species.2, 18, 23, 25, 26Although probiotics are typically unable to colonise the GITdue to competition with the resident microbiota, they stillhave beneficial effects during their transit through the gut.18Inflammation Immune functionDigestive functionSystemic healthAllergies Skin conditions Weight gain/obesity Immune function Kidney function Cognition & behaviourAntibiotic induceddysbiosisAntibiotics are frequently prescribed in acute and chronicdigestive disorders with the goal of removing pathogenicbacteria.18 However, antibiotic administration can have seriousconsequences on the GI microbiome, inducing intestinaldysbiosis.18, 22 In particular, broad-spectrum antibiotics leadto a rapid and significant drop in the richness, diversity, andconsistency of microorganism groups found within the GITand there is often not enough evidence to justify their use.18, 21The intestinal dysbiosis can persist for several weeks to monthsfollowing cessation of antibiotic therapy, and in many cases,has long term impacts with a return to the initialcomposition rarely fully achieved.7, 12, 21, 22Probiotics produceimmunomodulatorymetabolites, antimicrobialpeptides and proteinsModify and stimulatethe growth of thelocal microbiotaProbiotics enhance themusosal integrity of theintestinal epithelial barrierPrevent againstadhesion andcolonization bypathogensProbiotics suppressinflammation by reducingthe overall activity ofNuclear Factor kβ (NF-kβ)and the production of proinflammatory cytokines.Modulate the hostimmune systemPrebiotics are non-digestible ingredients, like fibre, thatsupport the growth and health of the host’s residentmicrobiota.10 They could also be described as ‘the foodfor our local beneficial bacteria’. Prebiotics are selectivelyfermented in the GI tract, enabling specific alterations in thecompositions and activity of the resident microbiota.2,10Probiotics supply an exogenous source of live bacteria tothe host and when combined with prebiotics, the synergisticcombination is known as a ‘synbiotic’.2

Yeast as probiotics:Saccharomyces BoulardiiUntil now, practitioners have faced the challenge of commercial and veterinary probiotic products not being listed forconcurrent use with antibiotics. This has been especially problematic in cases of AAD commonly seen in practice.2 Yeast arenaturally resistant to antibiotics, which sets them apart from probiotics of bacterial origin.9Saccharomyces cerevisiae boulardii (S. boulardii) is a strain of yeast which has been extensively studied in both humans andanimals over the past decade for its therapeutic probiotic effects.9 It is non-pathogenic and is antibiotic-resistant, so thereforecan be prescribed concurrently to patients receiving antibiotics.9 S. boulardii also has a temperature optimum of 37 degrees,which is close to the physiological temperature of dogs and cats to enable survival on its transit through the GIT. Furthermore,it is resistant to local stresses such as the presence of GI enzymes, bile salts, organic acids and considerable pH variations whichare the hallmarks of an effective probiotic.13The mechanisms of action of S. boulardii in the intestinal lumen are abundant, with a variety of positive and protectiveeffects achieved.27 It degrades toxins released by pathogens, interferes with the adherence of pathogenic bacteria along theGIT, modulates normal microbiota by supporting the establishment of beneficial bacteria and preserves normal intestinalphysiology.27 It also directly restores normal short chain fatty acid (SCFA) balance, vital in the regulation of intestinal motility.2, 8In addition, S. boulardii increases mucosal surface antibody levels and decreases inflammatory mediators, optimising both theinnate and adaptive immune systems to maintain overall health.19 Consequently, S. boulardii has received noteworthy attentionas a preventative and therapeutic agent for diarrhoea and other digestive disorders.13Destructive effects of pathogenic microbes1 T oxins increasewater secretion2 Bacteria(especially E.coli) destroytight junctions &invade mucosa112a22b2b34 V iral infectiondestroys matureenterocytes45 Decrease indisaccharidasecauses osmoticdiarrhoea5 etabolic activity3,4 4 MSB increases short chain fatty acids, favouringnormal colonic functionSCFACell growth and viability effects5a 5 E nzymatic activity5b65b6S. boulardii7 InflammationLuminal action1 A nti toxin EffectNeutralization of C. difficile toxins (A and B) andE. coli LPS (63 kDa protein phosphatase)2 A ntimicrobial activity(a) Preservation of tight junctions(b) S B binds pathogenic bacteria, preventing invasion3 Modulation of intestinal flora3 Intestinal floradepleted byantibiotics6 Decreasein IgAProtective effects of S. boulardii (SB)771 C . difficile toxinsand E. coli LPS3 Intestinal flora2 Pathogenicbacteria4 V iruses destroyingenterocytes(a) S B upregulates polyamine synthesis, favouringenterocyte maturation(b) I ncreased disaccharidase levels improve sugardigestion- beneficial in viral diarrhoeaAnti inflammatory effect on intestinal mucosa6 I ncreased sIgA levelsImmune defence in the gut enhanced7 D ownregulation of inflammatory cytokinesOccurs via the modulation of cellular signallingpathways5a P olyamines6 P athogens5b S ugar6 S ecretory IgA(sIgA)

Combating antibiotic resistancewith probiotic yeastAntimicrobial resistance is a global issue which impacts the future of both human and animal health.1 Resistant genes may betransferred between resident bacteria in the hosts’ gut microbiome but also to and from transient bacterial probiotics. Consequently,genes conferring resistance to tetracycline, erythromycin and vancomycin have been detected in Lactobacilli and Enterococciprobiotic strains.13 On the contrary, no gene transfer occurs between bacteria and yeast. This lack of gene transfer, as well as yeasts’natural resistance to antibiotics, highlight the superiority of probiotic yeast over probiotic bacteria when antimicrobials are involved.2, 13Saccharomyces boulardii inthe management of acute andchronic digestive disordersSaccharomyces boulardii: An effective probiotic inthe prevention and treatment of antibiotic-induceddiarrhoea (AAD) in dogs28Group IGroup IITwenty-four dogs of variable breed, sex and age were dividedinto three equal groups: groups I, II and III. Dogs in groups Iand II received intramuscular (IM) injections of the antibioticlincomycin (150mg/kg/day) until diarrhoea occurred.Following the onset of diarrhoea, all dogs in group II, weregiven 1000mg/day of S. boulardii orally for 10 days. Dogs ingroup I (control group) did not receive S. boulardii. Dogs ingroup III were given IM lincomycin at the same dose and 1000mg/day of S. boulardii orally for 10 days simultaneously. Noneof the dogs in group III developed diarrhoea, whereas 75% ofdogs in group 1 and 87.5% of the dogs in group II developeddiarrhoea as a side effect to lincomycin.01235467Duration of diarrhoea (days)200Group I180mmol/L160Group II140120In a prospective, non-randomised, double-blinded, placebocontrolled study, the effects of S. boulardii were evaluatedin four healthy control dogs and 20 dogs with chronicenteropathies (CE).Healthy controls received S. boulardii at 1x 109cfu/kg twicedaily for 10 days. Faecal samples for culture were collectedthroughout the treatment period. S. boulardii was presentin the faeces from day one of treatment, and a steady statewas reached at day five. No short-term adverse effects werereported by owners.Dogs with CE were all treated with diet, antibiotics andsteroids, and either S. boulardii at the same dose as the healthycontrols, or a placebo. Significant improvements in bodycondition score (BCS), the overall Chronic Enteropathy ClinicalActivity Index (CCECAI) score, as well as the stool consistencyand stool frequency, were noted in dogs with CE receiving S.boulardii vs the myces boulardii achieves better controlof clinical signs in dogs receiving treatment forinflammatory bowel disease5CCECAI ScoreFigure 1. Duration of diarrhoea in groups I and II. Theduration of diarrhoea in group II dogs was significantlyshorter than that of group I, showing the effectiveness oftreatment with S. Boulardii. None of the dogs in group IIIdeveloped diarrhoea.In short, a decrease in TSCFAs was demonstrated to bethe cause of diarrhoea in dogs treated with lincomycin. S.boulardii proved to be an effective probiotic cure for AADwhen given after the onset of diarrhoea and also an effectiveprophylactic when given together with lincomycin from thecommencement of antibiotic ion1W aftertreatmentFigure 2. Mean values of total short chain fatty acids(TSCFAs) in groups I and II. At both time points in relationto diarrhoea cessation and one week after treatment, theTSCFAs were significantly higher in group II than they werein group I. Group III is not represented as they did notdevelop diarrhoea and showed no significant change inTSCFAs 1 week post treatment vs baseline readingT30T45T60Saccharomyces boulardiiFigure 1. CCECAI negative outcome predictor scores indogs receiving S boulardii improved significantly comparedto dogs receiving a placebo at day 45 of treatment (T45)and day 60 (T60). In dogs receiving S boulardii, the CCECAIscore was significantly decreased (P 0.01) at days T14, T30,T45 and T60 compared to the baseline score at day 0. S.boulardii can be supplemented to achieve better control ofclinical signs in dogs treated for CE, compared to standardtherapy alone, without adverse effects.

Choosing the right PAW probioticfor your patientPAW Digesticare:Multi strainprobiotic &wholefood powderPAW Digesticare is a highly palatablepowder that combines a multi-strain,multi- species probiotic powder at 60million CFU/2g with a fermented fibrerich powder.Provides beneficial bacteria and fibreto establish, restore and support thelong-term health and function of the GImicrobiome in dogs, cats & pocket petsby sprinkling over either wet or dry fooddaily.Active ingredients:Probiotics: Lactobacillus acidophilus;L.delbrueckii subspecies bulgaricus;L.plantarum; L. rhamnosus;Bifidobacterium bifidum; Enterococcusfaecium; Streptococcus alivariussubspecies thermophilusFermented wholefoods: Naturallyfermented organic whole grains andseeds, alfalfa grass, quinoa, spirulina,sweet potato and additional legumesand cereals to provide easily absorbed,fibre-rich nutritional support.Dosage: Each level scoop contains 4gPAWDigesticare SB:Gastrointestinalsupport for usewith antibioticsDosageMaintenance(for daily administration)Puppies/kittensSmall dogMedium dogLarge dogCatsOther companion animals(rabbits, ferrets)2g2g4g6g2g2gIn periods of intestinal discomfort, doublethe dosage for the first five daysSize: 150g tubStorage: Keep below 25 C If the product is stored underrefrigerated conditions (below 8 C),the expiry date can be extended by12months.Warnings/Safety: For animal use only PAW Digesticare should not beused in conjunction with penicillins,cephalosporins, tetracyclines, avoparcin,gentamycin, lincomycin, streptomycin,tiamulin or tylosin.PAW Digesticare SB contains 10 billion CFU of Saccharomyces cerevisiae (boulardii),a probiotic yeast shown to reduce the duration & occurrence of antibioticassociated diarrhoea.Provides adjunctive therapy to improve clinical signs in dogs with chronicenteropathies compared to standard therapy alone.Only probiotic available in the Australian veterinary market that is not impacted byantibiotics.The two-part vegie capsule is simple to administer- simply open and sprinklepowder over the dog’s food daily.Active ingredients:Each 500mg capsule contains 10bn CFU Saccharomyces cerevisiae (boulardii)Dosage: Daily dosage of 1-2 capsules for any sized dogSize: 30x 500mg capsulesStorage: Store below 30 CWarnings/Safety: For animal use only For veterinary supply only Use with caution in pregnant or lactating animals as safe use in pregnant andlactating animals has not been established

Choosing the right PAW probioticfor your patientPAW DIGESTICARERe-balance gastrointestinal microbiome In conjunction with antibiotic therapy (short/ long term) Treatment of antibiotic associated diarrhoea (AAD) Acute uncomplicated GI disordersImmunomodulation Modulation of chronic enteropathies (CE) in dogs concurrent medications Modulation of CE in untreated catsSupport a healthy GI microbiome Kittens, puppies and adult cats and dogs Pocket pets (guinea pigs, ferrets, rabbits)PAW DIGESTICARE SB

Introducing the PAW Practitioner rangeDeveloped for vets, by vets.1. Safetyandquality.gov.au. 2020. Third Comprehensive Report On Antibiotic Resistance Identifies Ongoing Threat Australian Commission On Safety And Quality In Health Care. [online] Availableat: https://www.safetyandquality.gov.au/media resistance-identifies-ongoing-threat [Accessed 22 May 2020]. 2. Jensen AP, Bjørnvad CR.Clinical effect of probiotics in prevention or treatment of gastrointestinal disease in dogs: A systematic review. J Vet Intern Med. 2019;33(5):1849-1864. doi:10.1111/jvim.15554 3 Marshall-JonesZV, Baillon ML, Croft JM, Butterwick RF. Effects of Lactobacillus acidophilus DSM13241 as a probiotic in healthy adult cats. Am J Vet Res. 2006;67(6):1005-1012. doi:10.2460/ajvr.67.6.1005 4.Hill’s Pet Nutrition. 2020. Dog Diseases - Gastrointestinal Disorders Hill’s Pet. [online] Available at: astrointestinal-and-digestive-problems [Accessed 22 May 2020]. 5. D’Angelo S, Fracassi F, Bresciani F, et al. Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study. Vet Rec.2018;182(9):258. doi:10.1136/vr.104241 6 Gómez-Gallego C, Junnila J, Männikkö S, et al. A canine-specific probiotic product in treating acute or intermittent diarrhea in dogs: A double-blindplacebo-controlled efficacy study. Vet Microbiol. 2016;197:122-128. doi:10.1016/j.vetmic.2016.11.015 7. Suchodolski JS. Companion animals symposium: microbes and gastrointestinal healthof dogs and cats. J Anim Sci. 2011;89(5):1520-1530. doi:10.2527/jas.2010-3377 8. Blake, Amanda & Suchodolski, Jan. (2016). Importance of gut microbiota for the health and disease of dogsand cats. Animal Frontiers. 6. 37. 10.2527/af.2016-0032 9. Suchodolski JS. Diagnosis and interpretation of intestinal dysbiosis in dogs and cats. The Veterinary Journal. 2016;215:30-37. doi:10.1016/j.tvjl.2016.04.011 10. Yousefi B, Eslami M, Ghasemian A et al. Review article: Probiotics importance and their immunomodulatory properties. J Cell Physiol. 2019;234:8008-8018. doi:10.1002/jcp.27559 11. Barko PC, McMichael MA, Swanson KS, Williams DA. The Gastrointestinal Microbiome: A Review. J Vet Intern Med. 2018;32(1):9-25. doi:10.1111/jvim.14875 12. Redfern A,Suchodolski J, Jergens A. Review: Role of the gastrointestinal microbiota in small animal health and disease. Veterinary Record. 2017;181(14):370-376. doi: 10.1136/vr.103826 13. L. V. McFarland& P. Bernasconi (1993) Saccharomyces boulardii’. A Review of an Innovative Biotherapeutic Agent, Microbial Ecology in Health and Disease, 6:4, 157-171. doi: 10.3109/0891060930914132314. Kelly, M. The Role of Probiotics in GI Tract Health. Purina Probiotic Manual. 2006 15. Mondo E, Marliani G, Accorsi PA et al. Role of gut microbiota in dogs and cat’s health and diseases. OpenVet J. 2019;9(3):253-258 doi: 10.4314/ovj.v9i3.10 16. Wernimont SM, Radosevich J, Jackson MI, Ephraim E et al. The effects of nutrition on the gastrointestinal microbiome of cats and dogs:impact on health and disease. Front in Microbiol. 2020;11:1266. doi: 10.3389/fmicb.2020.01266 17. Belizário JE, Faintuch J. Microbiome and Gut Dysbiosis. Exp Suppl. 2018;109:459-476.doi:10.1007/978-3-319-74932-7 13 18. Pilla R, Suchodolski JS. The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease. Front Vet Sci. 2020;6:498.Published 2020 Jan 14. doi:10.3389/fvets.2019.00498 19. Suchodolski JS. Intestinal microbiota of dogs and cats: a bigger world than we thought. Vet Clin North Am Small Anim Pract.2011;41(2):261-272. doi:10.1016/j.cvsm.2010.12.006 20. Czerucka D, Piche T, Rampal P. Review article: yeast as probiotics -- Saccharomyces boulardii. Aliment Pharmacol Ther. 2007;26(6):767778. doi:10.1111/j.1365-2036.2007.03442.x 21. Doidge C, Hudson C, Lovatt F, Kaler J (2019) To prescribe or not to prescribe? A factorial survey to explore veterinarians’ decision makingwhen prescribing antimicrobials to sheep and beef farmers in the UK. PLoS ONE 14(4): e0213855. https://doi.org/10.1371/journal.pone.0213855 22. Shmalberg J, Montalbano C, Morelli G,Buckley GJ. A randomized double blinded placebo- controlled clinical trial of a probiotic or metronidazole for acute canine diarrhea. Front Vet Sci. 2019;6:163. doi: 10.3389/fvets.2019.0016323. Proplanvetdirect.com. 2020. Fortiflora Probiotic Supplement For Dog Diarrhea Pro Plan Vet Direct. [online] Available at: -probiotic [Accessed 22 May 2020]. 24. Tanprasertsuk J, Jha AR, Shmalberg J, Jones, RB et al. The microbiota of healthy dogs demonstrates individualised responses to symbiotic supplementation in arandomized controlled trial. An Microbiome. 2021;3:36. doi: 10.1186/s42523-021-00098-0 25. Vet, P., 2020. Synbiotic D-C. [online] Protexin Vet. Available at: https://www.protexinvet.com/synbiotic-d-c/p6229 [Accessed 22 May 2020]. 26. Vet, P., 2020. Pro-Kolin . [online] Protexin Vet. Available at: https://www.protexinvet.com/pro-kolin/p6230 [Accessed 22 May 2020]. 27.McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010;16(18):2202-2222. doi:10.3748/wjg.v16.i18.2202 28. FCAktaş,Mustafa & Borku, Mehmet & Ozkanlar, Yunusemre. (2007). Efficacy of Saccharomyces boulardii as a probiotic in dogs with lincomycin induced diarrhoea. Bulletin- Veterinary Institute in Pulawy.51. 365-369BLK50746References

Digestive disorders behavioural in dogs and cats Digestive disorders are common in companion animals and cause stress to both pet and owner.3 Any condition that reduces the digestion or absorption of food, or alters its transit through the digestive tract can be considered a digestive disorder.4 In practice, veterinarians are most

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