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Use of probiotics and prebiotics in dogs with antibiotic-associated gastrointestinal signs | VETgirl Veterinary Continuing Education Podcasts

In this VETgirl online veterinary continuing education podcast, we review the use of synbiotics as a therapeutic strategy in dogs with antibiotic-associated gastrointestinal signs (AAGS). As a quick reminder, synbiotics are a combination of probiotics and prebiotics. Probiotics are defined as products that contain viable microorganisms that are used with the intention of altering the host’s microflora in order to confer some sort of health benefit, whereas prebiotics are a type of ingredient that is designed to benefit the host by stimulating the growth or the activity of bacteria (Schrezenmeir). The use of probiotics, prebiotics, and synbiotics are thought to potentially help AAGS by replenishing the gut flora that was damaged by antimicrobial administration. Unfortunately, AAGS is common, and such side effects can impact owner compliance when administering antibiotics. This is of particular importance because incomplete courses of antibiotics can lead to impaired patient outcomes and the development of antimicrobial resistance.

So, Whittemore et al wanted to investigate the impact of probiotic/synbiotic administration in dogs with AAGS in a study entitled Randomized, controlled, crossover trial of prevention of antibiotic-induced gastrointestinal signs using a synbiotic mixture in healthy research dogs. This was a randomized, double-blinded, placebo-controlled, 2-way, 2-period, crossover study. The study used clinically healthy research dogs that consisted of two breed groups – Hound and Beagle. The dogs were then randomized using a computerized random number generator into two groups: group A and group B. The screening process included a physical examination, ivermectin and fenbendazole administration, observations by investigators twice daily, and a diagnostic evaluation that consisted of complete blood count (CBC), serum biochemistry panel, urinalysis, fecal direct smear, and sugar and zinc sulfate fecal flotations.

In terms of treatment, a probiotic/synbiotic combination was used, which consisted of 1 chewable Proviable, which is a multistrain bacterial probiotic, and 1 chewable Mycequin tablet, which is a yeast synbiotic. Placebo tablets were the same size, shape, smell, and flavoring. All dogs were fed approximately 13g of canned, commercial, adult dog food, which was initiated prior to the start of the study so that a concurrent diet change would not impact clinical changes. The dogs were all started on oral enrofloxacin (10 mg/kg once daily) and oral metronidazole (12.5 mg/kg twice daily). Then dogs in one group received 2 chewable placebo tablets an hour after receiving antibiotics, and dogs in the other group received 2 chewable probiotic/synbiotic tablets an hour after antibiotics. This regimen continued for 4 weeks, followed by the 8-week washout period, then switched to the alternative treatment regimen for another 4 weeks. A blinded observer evaluated each dog two times daily. They documented information regarding vomiting, fecal score, body weight (measured weekly), and food intake. Treatment was stopped if the dogs became too ill based on predetermined criteria. For instance, if dogs reduced their food intake to less than 50% of baseline for more than 2 days, if 2 or more piles of vomitus were noted for 3 days in a row, or if a dog lost 6% of their body weight or more within a week, the treatment was stopped.

A total of 22 dogs made it into the study after the initial screening phase, which provided 11 dogs per group. All dogs were 1 year of age, and each group consisted of 6 intact female Hound dogs and 5 male neutered Beagles. The median weight was identical at 9.3 kg for each group. Group A dogs received the placebo in the first period of the study, followed by the probiotic/synbiotic combination after the washout period. Group B had the opposite regimen. In group A, 1 dog was removed after the first week of treatment in period 1 (ie, after a week of receiving placebo) due to weight loss. The dog also had an intermittent appetite and occasional vomiting. Then after a week of period 2 (ie, after a week of receiving the probiotic/synbiotic), the dog was again removed for weight loss. No other dogs in either group had to be removed from the study.

So, what did the investigators find? Well, all dogs included in the study suffered from AAGS. In fact, in period 1 of the study, 41% of dogs had a diminished appetite, 77% experienced vomiting, and 100% developed diarrhea. Vomiting was the worst during the first week of antibiotic administration. Wow, those antibiotics can be rough! This level of adverse effects does raise concern that it could impact owner compliance in a real clinical setting. The mean food intake did significantly differ between the two treatment groups, in that dogs receiving the probiotic/synbiotic had less alterations in appetite in both periods than those receiving the placebo. Furthermore, marked decreases in appetite were 7 times more likely in period 1 than in period 2. Dogs receiving the probiotic/synbiotic also had lower fecal scores in period 2. This reduction in hyporexia and the lower fecal scores in period 2 could suggest that the probiotic/synbiotic has sustained effects even after discontinuation, but unfortunately the authors cannot rule out that the dogs simply acclimated to antibiotics. Vomiting and fecal scores in period 1 were not substantially different between treatment groups. It is important to note that this study only included healthy, young dogs, so it is possible that the use of older dogs or those with systemic disease could impact results. The authors also discuss that since the dogs did not have 24/7 observation, the vomiting episodes could have been over or underestimated.

So, what can we take away from this VETgirl podcast? Well, perhaps one of the more dramatic findings was the pronounced AAGS noted in this study population, particularly given that the investigators used fairly standard antibiotic dosing regimens. The results of this study also suggest that the use of a probiotic/synbiotic could potentially help mitigate the impact of antibiotics on appetite, and possibly even have prolonged effects on appetite and fecal scores. However, this is still somewhat uncertain, and unfortunately there was no obvious impact on vomiting. That said, both Vetgirl and the authors would caution you against expanding the results of this study to other dosing regimens or to other probiotics, synbiotics, or antibiotics. This study used healthy dogs and used very particular medication regimens, so it is difficult to know how these results will translate clinically without further investigation. That said, probiotics and synbiotics may be considered in dogs at risk of developing AAGS!

References:
1. Whittemore J, Moyers T, Price J. Randomized, controlled, crossover trial of prevention of antibiotic-induced gastrointestinal signs using a synbiotic mixture in healthy research dogs. J Vet Intern Med 2019;33(4):1619-1626.
2. Schrezenmeir J, de Vrese M. Probiotics, prebiotics, and synbiotics approaching a definition. Am J Clin Nutr 2001;73:361S-364S.

Abbreviations:
AAGS – Antibiotic-associated gastrointestinal signs
CBC – Complete blood count

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