I have written about probiotics previously (in general, for herpsvirus in cats, and some of the overhyping and quackery associated with them), and in general I have been cautiously optimistic about their potential, while criticizing claims that go beyond the data. I recently came across a couple of studies which illustrates some of the good positive research on probiotics and makes me more inclined to consider using them for specific conditions.
First Study
Kelley RL, Minikhiem D, Kiely B, O’Mahony L, O’Sullivan D, Boileau T, Park JS. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Veterinary Therapeutics 2009 Fall;10(3):121-30.
The first study is the better of the two for several reasons. The probiotic chosen was a strain of Bifidobacterium derived from dogs. One of the problems with the generally application of probiotics is the questionable logic of taking small amounts of an organism that does not normally live in the gut of a given species and cannot colonize it and giving this organism to “balance” the animal’s gut flora. Commensual organisms that already live in the gut, and which presumably share a history of mutual adaptation with the host, seem more likely to be beneficial in restoring a disturbed GI ecology. Previous research had been done to show this strain was able to survive passage through the stomach acid and colonize the intestine of the dog as well as to survive the processing and storage conditions used to create a product that can be shipped, stored, and given to patients. This groundwork greatly increases the plausibility of the intervention.
The subjects in this study all had acute diarrhea, and in most cases it was idiopathic, meaning no specific cause was found. This is the most common kind of diarrhea seen in clinical practice, and it usually gets better on its own within a week or so. The goal of the study, then, was to see if the probiotic helped dogs to get better sooner than those not treated at all. This, of course, is a valuable goal, but we must be careful not to confuse this use with treatment of diarrhea that is not self-limiting and might not get better without therapy, which is an entirely different problem and for which the value of probiotics would have to be demonstrated in a study specifically conducted for that purpose. Over-generalizing is a common error behind the use of novel or alternative therapies, and it is vital to remember that if a treatment is effective for, say acute self-limiting diarrhea, that doesn’t mean it is effective for chronic diarrhea, parasitic or infectious diarrhea, food allergy diarrhea, or any other different kind of diarrheal disease.
In this study, 31 dogs with were randomly assigned to receive either the probiotic or a matched placebo. All personnel involved in care and evaluation of the subjects were blinded to the treatment groups. All dogs were screened for parasites. 3 were found to have Giardia, and I was initially concerned that if these dogs had more severe disease and happened to be in the placebo group, they might create the false impression of a better outcome for the treatment group. I contacted the manufacturer of the product who contacted the lead author to inquire about this possibility. I was informed that 2 of these dogs were in the placebo group and 1 in the treatment group. These 3 subjects were analyzed to see if their symptoms were worse than the others (they were not) and when their results were removed from the analysis it did not change the outcome.
All the dogs were young (between 1 and 2 years of age) and residents of a guide dog colony. This allows for better control of variables such as diet, environment, breed, age, concurrent diseases and medications and so on. It also might make the results less applicable to other populations, but such are the tradeoffs of all research studies.
Some of the subjects in both groups received the anti-diarrhea antibiotic metronidazole. There were more dogs medicated in the control group than in the probiotic group. The authors acknowledge this is a weakness in the study, but the trend of the results was unchanged when the cases receiving this drug were excluded from the analysis (though this did not leave enough animals to make statistical comparisons).
For dogs in the placebo group their diarrhea resolved in an average of 6.6 days. The dogs in the probiotic group returned to having normal stools in an average of 3.9 days, and this difference was not due to chance alone based on the statistical analysis. This is enough of an effect that if it is consistent in other patient populations and circumstances, it would be a meaningful clinical benefit. Overall, this study provides good evidence for the benefit of this particular probiotic in acute, self-limiting, idiopathic diarrhea in dogs. Again, we must not assume this means that all probiotics are beneficial for all kinds of diarrhea in all patient populations.
Second Study
Herstad HK, Nesheim BB, L’Abée-Lund T, Larsen S, Skancke E. Effects of a probiotic intervention in acute canine gastroenteritis–a controlled clinical trial. J Small Anim Pract. 2010 Jan;51(1):34-8.
This study involves a slightly more realistic, and thus not as well controlled, patient population and treatment and monitoring system. There are also a few other problems with methodology that make this a weaker study.
The probiotic used was a mixture of 5 different organisms, some from pigs, soil, humans, and unknown origin. It is unclear from the paper what if any prior basic research was done to establish whether these organisms survive processing, storage, and stomach passage and if they can colonize the intestines of dogs. No attempt was made in this study to see if the probiotic had colonized the subjects.
36 dogs with diarrhea (22 of which also had vomiting) were seen at a single hospital and randomly assigned to the probiotic or placebo groups. Many were screened for bacterial or parasitic causes of diarrhea, but not all. The assessment of improvement was owner evaluation of when the last abnormal stool and the first normal stool occurred. This potentially introduces some question about the reliability of these outcome measures, though it is unlikely there would be a systematic error favoring one or other treatment group. The subjects in the probiotic group had had symptoms slightly longer than those in the placebo group before entering the study, though this difference was not statistically significant.
The time from start of treatment to the last abnormal stool was an average of 1.3 days in the probiotic group and 2.2 days in the placebo group. This difference barely reached statistical significance (P=0.45). The difference of 1 day in duration of symptoms might be clinically meaningful, though less so than the difference seen in the first study.
The time to resolution of diarrhea was shorter than in the previous study, but this was for dogs who did not start treatment until they had symptoms for an average of 2-3 days, unlike the other study in which dogs with diarrhea were identified and began treatment immediately because they were residents in a colony with professional caretakers. If you count the time from onset of symptoms to end of symptoms, it was 6.1 days for placebo the group and 4.1 days for the probiotic group in this study, compared with6.6 for placebo and 3.9 for probiotic in the first study.
The other main measures looked at (time from start of treatment to first normal stool, number of stools, and duration of vomiting), there were no differences between the placebo and probiotic groups. Overall, then, this study found 1 marginally significant difference between probiotic-treated and placebo-treated dogs out of 4 outcome measures, which is a pretty weak showing.
Conclusion
So these studies do provide some support for the potential benefits of probiotics for acute, self-limiting diarrhea in otherwise healthy dogs. The better of the two studies provides pretty good quality evidence for this use, though more work will have to be done to see if these results are confirmed in other populations and more real-world circumstances. The second study provided a hint of an effect, but the results were weak and not particularly convincing.
I’m inclined to agree with the authors of the first study that a product derived from normal dog intestinal flora and adequately studied to determine that it is viable through processing, shipping, storage, and passage through the stomach is more likely to have a meaningful benefit than other products, and I would be willing to recommend using this product for acute, self-limiting diarrhea pending further research to either confirm or challenge the limited results we currently have.
Overall, I’m still cautiously optimistic about probiotics, at least for acute, self-limiting diarrhea, and these studies encourage that optimism. Clearly, there is much more work to be done to define which organisms in what doses will benefit which patients, but as long as we are careful not to imagine these products as some kind of panacea and go beyond the available data, they seem to be reaching a point where judicious clinical use is reasonable.
