I have written about the subject of probiotics several times before, and this is one of the most interesting and active areas of research in scientific veterinary medicine. Unfortunately, probiotics are also illustrative of the unreliability of unregulated veterinary health products and the kinds of excessive claims often made without real evidence for such products.
An excellent new review of probiotics in small animal medicine has just been published. By way of leading up to the evidence and conclusions of this review, first I will give a quick review of my past articles on this subject:
- A normal microbial flora is beneficial, and perturbations in the normal flora are associated with disease, so the principle that manipulating the microbial ecology can affect health is reasonable.
- The normal microbial flora is complex and poorly understood, so how to appropriately manipulate it to achieve health benefits is not yet clear.
- Clinical studies in humans are mixed, showing benefits from some probiotic products for some conditions, no benefit in other cases, and inconclusive results for many products and conditions.
- There is little reliable research in companion animals regarding the safety or efficacy of probiotic products.
- The risks of probiotics are probably very low. Individuals with compromised immune systems are at greatest risk and should not be exposed to probiotics. There is some limited potential for these products to cause disease even in healthy individuals.
Probiotics for Herpesvirus Rhinitis, 2010
- So overall, the study provides little support for the thesis that Fortiflora boosts general immune function in a way that would be clinically useful for cats with FHV-1 rhinitis.
- The argument that probiotics “boost the immune system” in general is not a very convincing one, as illustrated in acritique of the concept by Dr.Mark Crislip at Science-Based Medicine.
- There is no clinical trial evidence that shows resistance to infectious disease can be enhanced in a healthy, normal person.
- Probiotics undoubtedly have some benefits, however the GI microflora and its role in immune function is a dazzlingly complex subject which science is only beginning to understand. Most of the normal organisms present in healthy people and animals have not been identified, and the ecological niche or function of these organisms isn’t known. The effect of tinkering with this complex system without understanding it is ultimately unpredictable, and the assumption that such tinkering must be beneficial is unwarranted.
- As our basic understanding of the topic improves, I hope targeted probiotic therapies for specific problems will continue to emerge. But at this point, there is little scientific justification for the widespread use of such products for nearly any condition with the assumption of safety and efficacy.
Primal Defense- An Example of Why I am Suspicious of Probiotics, 2010
- The use of science to try and justify Mr. Rubin’s unscientific nutritional theories are pure marketing, taking advantage of the respectability that real science has earned through the results it produces. His approach is ultimately based, as so much CAM is, on personal revelation, and supported primarily through anecdote and testimonial….Such a marketing approach can turn a potentially legitimate, if not yet ready for primetime, therapy like probiotics into pure quackery.
- Companies like Garden of Life illustrate why the unregulated supplement industry (aka Big CAM) is not onlynot entitled to the assumption of better ethics that they often receive, but it quite likely gets away with even more ethically questionable practices than the mainstream medical and diet industries, which are at least better supervised and regulated.
Encouraging Studies on Probiotics for Canine Diarrhea, 2010
- 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.
- 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.
Veterinary Probiotics- Sloppy Labeling and Poor Quality Control, 2011
- This study does not directly address the question of whether or not probiotics in general are actually safe and beneficial for clinical use in dogs or cats. But it does highlight that even if they are, most of the veterinary probiotics currently available are inadequately or improperly labeled and do not have meaningful numbers of active bacteria in them anyway. A lack of research evidence combined with a lack of effective regulation, due primarily to the lobbying efforts of the supplement industry, undermine the potential value of these therapies and make confident routine use of the products now on the market nearly impossible.
Probiotic Fortiflora Not Apparently Very Helpful in Preventing Diarrhea in Shelter Animals, 2011
- For the dogs, there was no significant different in the incidence of diarrhea between those getting the Fortiflora and those receiving the placebo regardless of how the data was analyzed. The overall incidence of diarrhea in both groups was lower than expected for reasons that were not identified.
- In the cat groups, the overall incidence of diarrhea was no different between the probiotic and placebo groups. However, when the data was broken down to compare the proportion of cats having diarrhea for more than 2 days, this was lower in the probiotic group than in the control group, though the level of significance was not dramatic (P=0.0297 with a cutoff of <0.05).
European Food Safety Authority Rejects Prostora, A Probiotic for Dogs, 2013
- In terms of the efficacy of the product, the EFSA concluded that it could not reach a definitive judgment. According to the report, eight research studies were submitted in support of efficacy. Five of these were rejected for inadequate methodology (lack of a control group, for example). The three evaluated (including one I have reviewed here) did show some evidence of a beneficial effect. However, the effects were inconsistent and not always strong enough to be meaningful even if statistically significant.
- Apparently, the organism in Prostora has shown some resistance to the antibiotic clindamycin. A number of genes that confer antibiotic resistance have been identified, and some of these can be transmitted from one bacterium to another. The specific source of the resistance to clindamycin seen in the Prostora bacterium is not known, so it is not clear if this resistance could be transmitted to other bacteria in animals or people exposed to Prostora.
- Because of this uncertainty, and the serious and growing problem of antibiotic resistance in infectious organisms, the EFSA chose not to approve the sale of Prostora in the EU.
- As I have often said about probiotics, because they clearly have the ability to affect the health of people and animals, they undoubtedly have risks as well as benefits. The devil is in the details, and they should neither be rejected out of hand nor embraced unquestioningly as beneficial. The specific risks and benefits of particular organisms for particular health conditions in particular species have to be understood through the careful and laborious process of scientific research. There is nothing intrinsically “alternative” about the use of microorganisms to affect health, but the indiscriminate use of them in the absence of appropriate scientific evaluation would be a mistake in the tradition of the worst kind of alternative medicine.
- The authors conclusions are these:
Although probiotics have shown promise in the treatment of selected diseases in humans, the evidence that they can be used to control diseases in horses so far is weak.Based on lack of regulation regarding quality control of commercial products, use of over-the-counter products is questionable, particularly in the absence of scientific information on safety and clinical efficacy.Despite all of these limitations, probiotics generally are regarded as safe, cost effective and easy to administer. Therefore, additional research is warranted to test possible applications in equine veterinary practice.
- Very similar conclusions likely apply to the use of probiotics in small animals. They are probably low risk and are relatively easy to use and inexpensive. In most cases, there is little evidence that they have significant benefits, but their use for some conditions, such as diarrhea, is reasonable given the limited but suggestive evidence available so far.
Clearly, over time I have gradually become more optimistic about the potential for probiotics as the evidence has accumulated. Unfortunately, the evidence is still quite limited and weak in small animals, and the issue of quality control and regulation has not been solved, so there is still significant uncertainty in the use of probiotic products in patients.
The recent review addresses some of the same studies I have discussed, as well as additional research. It is a sound, science-based summary of where we are today in terms of the scientific study and use of probiotics in small animal medicine.
Jugan MC. Rudinsky AJ. Parker VJ. Gilor C. Use of probiotics in small animal veterinary medicine. JAVMA. 2017;250(5):519-528.
The authors begin by discussing the general issues of investigating probiotics, including the problems with labeling and quality control, the importance of focusing on specific organisms and specific health conditions as well as recognizing the limitations of in vitro and artificial research models in predicting the effects in actual patients:
All 8 veterinary products evaluated in 1 study contained concentrations for individual microorganisms that were < 2% of label claims; such products also contained unlisted, potentially pathogenic genera (eg, Staphylococcus spp and Pediococcus spp). More recent studies on veterinary probiotic content have provided similar findings.
In vitro studies are useful for generating hypotheses for in vivo studies, but their clinical applicability is extremely limited ….
Importantly, the effect of a probiotic in a specific clinical context is likely unique to that context. For example, one cannot extrapolate the effect of a probiotic in dogs with a specific disease from results of studies on healthy dogs or on dogs with another disease.
Although studies of healthy dogs and cats frequently provide apparently positive effects of probiotics, the implication for disease states is unknown.
The authors then review the few studies that have been done in specific subject areas:
Acute GI Conditions
Overall, studies of dogs and cats with acute diarrhea provide weak evidence for the exclusive use of probiotics, yet provide substantial evidence for preventable stress-induced diarrhea…Evidence for use of probiotics in dogs and cats with naturally occurring acute diarrhea is lacking.
Chronic GI Conditions
Overall, there currently is no definitive evidence that probiotics are effective for dogs with chronic diarrhea, especially not dogs with more severe IBD.
Probiotics in Puppies and Kittens
Studies of puppies and kittens have limitations similar to those for studies of adult dogs and cats, including small numbers of subjects, limited evaluations for disease states, and limited control populations for direct comparison. One important feature, which is highlighted when puppies and kittens are concurrently evaluated, is that important species differences in response to probiotics exist; therefore, evidence from one species cannot automatically be extrapolated to another species. Probiotics are also likely to have different effects in immature animals than in adult animals because the GIT microorganism population transitions to the adult microorganism population during development in immature animals.
Kidney Disease in Cats
I have discussed several studies looking at the probiotic Azodyl, and despite the anecdotes and angry denials of some users, there is no reason to think this product has any benefits. The authors of this review appear to agree:
Taken together, the effect of probiotics on renal function in these studies is questionable.
…there currently are no indications for administration of probiotics to cats with chronic kidney disease.
General Conclusions
The overall assessment of the evidence in this review is pretty similar to my view that the evidence is limited and weak and, while encouraging for some conditions and organisms, is not yet clear about the real benefits, if any, of probiotics. Further research is certainly warranted, and clinical use may be appropriate in some circumstances, but we have yet to convincingly demonstrate meaningful benefits of probiotics to prevent or treat illness in dogs and cats.
….most studies have limitations, including the number of subjects, extent of population characterization, appropriate characterization of underlying disease, control of potential confounders (diets and other environmental effects), and comprehensive examination of potential outcome measures. Also, many studies are uncontrolled or use inappropriate or incomplete control groups.
A clear role for administration of probiotics to dogs and cats is not evident on the basis of the current literature. Evidence in healthy dogs, as well as dogs with GIT and non-GIT illness, suggests some effect of probiotics on the GIT microbial population,…but there are no clear clinical benefits. Similar but weaker evidence is available for cats, but with fewer controlled studies.
Although general conclusions can be drawn for a specific study population, results were variable among studies, and some studies indicated no effect of probiotics.
Currently, evidence suggests that administration of probiotics may play a role in animals with acute GIT disease, especially stress-induced diarrhea, mainly for decreasing the time until resolution of clinical signs when compared with outcomes for standard treatments.
Results for studies of dogs with chronic enteropathies are more difficult to interpret because they are typically confounded by administration of concurrent treatments.
On the basis of examination of the current data, no specific product can be recommended for use. Effective probiotic species are likely disease- and individual-specific microorganisms. Because of questions regarding accuracy of product labeling, products should be evaluated by outside laboratories. Longterm outcomes and administration periods require evaluation for both safety and efficacy.
Risks of Probiotics
The authors are clear that the existing evidence, while limited and weak with regard to benefits, does not suggest any common or serious risks, and I agree:
No substantial adverse effects were noted after probiotic administration in any of these studies, which suggests relative safety over a short period for the microbial populations evaluated.
Bottom Line
This review provides a concise survey of the probiotic research in dogs and cats to date, including an appraisal of the significant weaknesses and limitations on the existing studies. The bottom line is consistent with my own view of the literature.
- There are few studies, and those that have been done have significant limitations and often conflict.
- There is reasonable evidence for some clinical benefit in acute diarrhea associated with stress or antibiotic use.
- There is no high-quality, consistent evidence for most suggested uses of probiotics.
- The unregulated probiotic products on the market today are plagued with inaccurate labeling and poor quality control. This means that even if probiotics might be beneficial in some cases, it is unclear if the actual products available could achieve these benefits.
- There do not yet appear to be significant risks to probiotics, though the evidence for this safety also quite limited.
No Good News for Veterinary Probiotics, 2019
- the evidence points toward a limited and possibly clinically unimportant effect for prevention or treatment of acute gastrointestinal disease.
- for chronic gastrointestinal disease, dietary intervention remains the major key in treatment, whereas probiotic supplement seems not to add significant improvement
- this conclusion is based on a limited number of studies, with a wide methodological diversity, and mainly low sample sizes.
- there is a high risk that most of the studies evaluated in the current review were severely underpowered especially taking into consideration that baseline characteristics of study groups were generally very poorly documented
- 12 of the [17] studies reported industry involvement; with such a high degree of industry involvement, there is a risk of publication bias as the incentive to publish studies showing no effect of probiotics could be low
At this point, the best we can say about probiotics is that they might be useful but we don’t yet have real evidence to show this, individual products are often mislabeled and quality control is poor, and the risks appear to be low but these haven’t been effectively studied. Ten years since I first wrote about this subject, that is a disappointing level of evidence, and it is frustrating to still be guessing about this treatment.
I wonder, with the new data coming from the Purina Study about higher protein diets affecting gut flora, will impact the efficacy or non efficacy of probiotic supplements. THe Pruina study was very preliminary with a small sample size so there wasn’t much to take from it but if higher protein diets affect flora how will this effect supplementation with probiotics.
Not to mention how soluble and insoluble fiber in dogs diets affects gut lining and flora increases or decreases depending on percentage of DM.
At least to me, it seems that the gut is ridiculously complex that throwing a few billion CFU of a probiotic seems quixotic.
I’d agree with that Paul. The evidence in humans does seem to be that diet has a large effect on gut flora and while one must obviously be careful about extrapolating from human to other animals it wouldn’t be surprising if diet affected the gut flora in other animals – at least in ones that can have varied diets. It seems to me that there is still a lot of work to do before we have any clinically useful applications.
There are so many problems with this research though. The shelter dogs could’ve had diarrhea because of stress instead of because of a gut and balance. Also, the dose might not have been a large enough. A lot of people who find benefits do so through fermented foods which have billions of more probiotics in them then supplements. The only problem is that you can’t control which probiotics you get in fermented foods unless you use a starter culture. Some people theorize that the fat in fermented food protects probiotics from stomach acid and that they go into your stomach with extra food so they can continue to multiply better. There could also be some bacteria that are probiotics that we don’t know about yet. There actually have been some humans who have had bad, incurable diarrhea who were able to be cured by fecal transplants from healthy individuals. The procedure is not common, but licensed G.I. doctors have been doing them for their most difficult patients at times. Also, some strains could do things that might not be readily apparent in a short term study. They might have some sort of virus protecting affect for example, or maybe some only work against certain viruses, but without exposure, we would never know. Some strains might also do other things like influence your hormones somehow and affect your mood, but that would be hard to know with animals. Maybe some strains are supposed to protect against parasites, but because the person being studied doesn’t actually have parasites, they seem useless. I’m not saying this is what the strains actually do. I’m just providing a hypothetical example of why it might be very hard to study. I do know that some studies have been done to show that antibiotics cannot kill probiotics, so it could mean that they have some sort of way to fight viruses and threats that they can confer to the host in someway. Another bad reason for using shelter dogs in a study is that when they arrive to the shelter, they will immediately be switched to a food that they are not used to, and because the weaning process was not completed correctly, that can cause diarrhea for a week or two.
Sure, negative results can always reflect some underlying confounding factor not considered by the investigator. The studies don’t show probiotics in general don’t work, only that the specific probiotics used in these negative studies for specific purposes in that population didn’t work. That’s always the case with science.
However, the reverse is also true. Many positive studies involve multiple probiotic organisms, prebiotic compounds, diet changes, etc. In these studies, we can’t necessarily know which ingredient or combination of ingredients was critical for achieving the improvement seen.
Ultimately, if we don’t have many studies that show benefits, we can’t just claim that there are benefits anyway and the studies didn’t look for them in the right way. The absence of good evidence means we can’t say with any confidence what benefits there are or aren’t, only that the theoretical potential has not yet been shown to be achievable in real patients except in some limited circumstances.
Fecal transplantation is a bit of a different subject, and I haven’t covered the evidence concerning that yet.
What do you think about soil based probiotics like Vetri science? Some articles I have read say they are better than dairy because they survive stomach acid better and multiply easier and they can also have a longer shelf life. However, other articles I have read say they do not belong in the body and they could become a pathogen and over run the other types of bacteria. What do you think?
Ultimately, we don’t have the research data to answer your questions. There have been cases of probiotic organisms causing infections, but only in individuals with severely abnormal immune systems, so that risk is probably very low. Whether one organism works better than another will have to be determined from research, which I wish these companies would be responsible enough to do before making a profit off of these untested products.
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So based on the information we currently have do you recommend probiotic usage for dogs? If so, in what circumstances?
Honestly every animal shouldn’t be in a shelter they should be in a family environment
What an informative post, I think like us humans, dogs also need probiotics for their gut too. But of course with professional guidance from your vet. I found this article and learned some good tips for our dogs [commercial link deleted]. Thanks
Skeptvet,
The year before I had to let go of my beloved dog, he suffered through many dental surgeries due to retained roots and other complications. During that year, he was put on rounds of antibiotics quite often. The following year he passed from a stomach bacterial infection. Now, I keep wondering if he had an unhealthy gut from the overuse of antibiotics. I’ve been told that probiotics used together with antibiotics is supposed to balance things out in the gut. Do you believe this to be true? I feel so guilty that I didn’t try them.
Angie, I’m sorry this happened to you. The idea that probiotics can reduce the side effects of antibiotics is a popular one, and there is some evidence for this. The problem probiotics may be helpful with, however, is mostly diarrhea, so serious or fatal infections in dogs and cats with antibiotic use are very uncommon, and I suspect there was something else going on in your dog’s situation.
The only new information since this article was written a couple of years ago is the following review, which did not find much evidence that probiotics are helpful in dogs and cats for preventing stomach and intestinal problems, so I don’t think you have anything to feel guilty about.
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
Thank you so much for the kind words and quick reply. I just realized the date of this article…it’s the exact date my baby passed. I also just read your new post regarding this matter. I had no idea that metronidazole is probably considered as an ineffective treatment for diarrhea. That is what they gave him during his infection. Ugh. I do agree that he may have had something else going on. I guess I just thought the overuse of antibiotics the year before caused his gut to become unbalanced. And maybe that’s one the of reasons he wasn’t strong enough to pull through the infection when it happened. I have so many unanswered questions regarding his passing, so it’s been extremely hard. I really appreciate your time.
Skeptvet,
In your new article regarding probiotics, you mention Metronidazole being ineffective for diarrhea. Is this drug ineffective for other issues as well?
Thanks
There are only three studies of metronidazole for diarrhea. One showed it added no benefit to another antibiotic for acute diarrhea, on showed no added benefit to a steroid for chronic diarrhea, and on showed no difference from placebo for acute diarrhea. It does have some efficacy for Giardia infections, and it is an appropriate antibiotic for many bacterial infections, so I’m not saying the drug is inherently ineffective, only that the evidence so far for use in diarrhea suggests it probably doesn’t have a benefit.
Okay thank you. My heart sunk when you said that because that’s what the vet gave my boy for his bacterial infection. Since he couldn’t fight it off and didn’t pull through, I feared that the antibiotic didn’t work for the infection when I read your findings. Like I said before, I have so many unanswered questions regarding his final days 🙁
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