Behavioral Probiotics

The gut’s primary job is complicated and critical – extracting nutrients from food and moving waste products out of the body – it’s a marvel of engineering. In recent decades, though, we’ve learned that the gut is even more complex and amazing than we previously knew: Researchers have discovered that the bacteria and fungi living in the gut can affect our behavior – or, more significantly to WDJ readers, our dogs’ behavior! 

GUT FEELINGS

The populations of bacteria, viruses, fungi, and microfauna that live on the canine (and human and rodent) body are known as the microbiome. You and your dog host multiple different environments with different populations of tiny beings living on you: on the skin, in the mouth, in the vagina if you’ve got one, and in the gut. 

The gut is a sort of tube running through you, and lining that tube is a dynamic ecosystem of various bacteria, helping digest your food, producing nutrients that you need, and, it turns out, affecting how you feel.

Evidence for a relationship between the gut and behavioral health is strong. Inflammatory bowel disease in humans is associated with anxiety and depression. Autism is associated with gut issues, as are many psychiatric illnesses. Antibiotics can kill off many of the bugs in our gut, and when they do, the risk of developing an anxiety disorder increases. Gut infections can also increase the risk of anxiety disorders. We know that the gut microbiome can affect the stress response, and that this relationship goes both ways – the stress response can also affect the bugs in our gut.

Normal, non-pathological personality traits also seem to change in concert with our gut bacteria. A 2020 study looked at 655 people who filled out online questionnaires and sent in fecal samples. They found decreased gut diversity in participants who reported having high stress levels and those who described themselves as “more conscientious.” Researchers also found increased gut diversity in people with larger social networks. They also identified specific bacterial species associated with people having particular personality traits.

These studies show correlations, that gut and behavioral health go hand in hand. But we still don’t know how this relationship works. Does anxiety cause gut dysfunction? Or does gut dysfunction cause anxiety? 

Studies in laboratory rodents show that fecal transplants (populating one mouse’s gut with the contents of another mouse’s gut) can change the recipient’s behavior to match that of the donor. 

In one study, researchers stressed mice until their behavior changed to demonstrate anxiety. Then they gave an unstressed population of mice fecal transplants from these anxious donor mice. The previously unstressed population began displaying anxiety behaviors, apparently due only to the transplant of bacteria from stressed mice. Fascinating!

GUT REACTION

Okay, okay! Let’s discuss what matters most to us dog owners: Can we alter the bacterial populations in our dogs’ guts to change their behavior? 

We already commonly alter bacterial populations in dogs to promote gut health, either by giving carefully curated commercial probiotic supplements or less carefully curated supplements in the form of foods like yogurt, kefir, or kraut. Could we give probiotics that have not just gut health benefits, but behavioral health benefits, too?

Multiple studies have addressed this question in humans and laboratory rodents. Because a single study is limited in what it can tell us – it’s affected by the exact methods the researchers use, as well as a healthy helping of chance – the best evidence we have is a meta-analysis, a study that summarizes the findings of many other, smaller studies.

A 2018 meta-analysis by Reis et al. looked at a number of studies on the effects of probiotics on behavior in both humans (14 studies) and laboratory rodents (22 studies), and this summary study provides us with our best evidence about whether probiotics really can change behavior.

This meta-analysis pooled the results of all the laboratory animal studies and analyzed them together to see what the overall results were. Overall, probiotics did seem to work to change behavior in mice, but not rats, and then only in mice who were in some way unhealthy or stressed. (Some studies did show effects in rats or unstressed mice, but the overall results suggested that those studies showed effects only by chance.) As for humans, probiotics did not seem to have an effect in us either. 

The researchers had some insights into why studies in rats and humans might have shown no effect (or at least no consistent one), while studies in mice did:

* There may be a baseline of anxiety below which probiotics aren’t going to do much for you – you’re already behaviorally healthy. Surprisingly, none of the human studies included subjects who were actually suffering from anxiety!

* Measuring changes in the feelings of humans is difficult, requiring self-report tests, which are notoriously unreliable. Possibly, the humans taking probiotics did start to feel better but weren’t aware of it. In fact, studies suggest that when you’re coming out of depression or ongoing anxiety, you may start to have measurable improvements before you are consciously aware of them. Measuring changes in behavior in laboratory rodents is more objective, however, and therefore may have been more sensitive.

* Probiotics take time to work. Studies may not run long enough to see real changes; increased time equates to increased expense. Only half of the studies included in this meta-analysis lasted for at least eight weeks. Benefits in humans may have been seen in longer-duration studies.

* Dose may matter. The doses of probiotics given to mice, rats, and humans weren’t all that different, but when the massive differences in size of those species are taken into account, they differed wildly. Since the smallest animals showed the clearest effects, it may be that increasing dose makes probiotics more effective in larger animals.

* The researchers suggested that it’s possible that we need to give humans doses dozens or hundreds of times higher than what we are currently dosing! This suggests that doses in dogs may be low as well.

MARKET THAT HUNCH!

In January 2019, the first probiotic marketed for behavioral change in dogs, Calming Care, was released by Purina. It contains B. longum, strain BL999. (It also has liver in it, and my dogs report that it tastes very good; they lick it right up.) Calming Care is the only behavioral probiotic that has been tested in dogs, though many probiotics for gut (not behavioral) health are on the market.

Calming Care was tested by Purina, but the study was not published in a peer-reviewed journal. Summaries are available, but the detailed methods are not, meaning the specific methods used to test the probiotic aren’t public. This means the study’s results, in classic researcher-ese, are “difficult to interpret” – in other words, something could be confounding the results.

Here’s what we do know: The study involved 24 anxious Labrador Retrievers. For six weeks, dogs were given either B. longum BL999 (i.e., Calming Care) or a placebo; they were then tested for anxiety-like behaviors, heart rate, heart rate variability, and salivary cortisol. (The specifics of the behavior tests are not available.) The dogs were taken off the supplement for three weeks, after which the two groups were switched, and each group received the other treatment (probiotics or placebo) for another six weeks. Both groups were tested a second time. The results were impressive:

* 22/24 treated dogs showed significant reduction in barking, jumping, spinning, and pacing compared to their behavior on placebo.

* 20/24 treated dogs had smaller increases in salivary cortisol (a hormone that is elevated in response to stress) when they exercised and when they were exposed to anxiety inducing stimuli compared to their behavior on placebo.

* 20/24 treated dogs had increased heart rate variability (which is a sign of decreased stress) compared to the behavior on placebo.

REAL WORLD USE

These numbers are very good – surprisingly good in light of the results seen in the meta-analysis discussed earlier. Two vets who prescribe Calming Care for their canine patients reported to me that it seemed to help about half the dogs they tried it on. However, they warned that while it’s worth trying, its effect is not as powerful as a prescription medication in a dog with significant anxiety.

There’s a gap between Purina’s research results and the experience of the two clinicians I know – a gap that could be explained in a few ways. The difference could be accounted for by the objective testing performed by Purina’s researchers, as compared to the owner reports used by the veterinarians. It’s possible that all the Labradors in the Purina study had a biologically similar form of anxiety that responds well to probiotics, but that is seen in only half of the anxious dogs in the real world. Possibly there was a problem with Purina’s study that made its results look better than they really were. The real question is, will Calming Care help your dog?

Probiotics are very safe and unlikely to have negative effects, so it’s worth trying to find out. Purina recommends a trial of at least six weeks before deciding whether the supplement works, but it’s worth running your trial for at least eight weeks.

Some owners want to try behavioral probiotics but don’t want to use Calming Care; some dogs are allergic to liver (one of its ingredients). There are many probiotics marketed for reducing human anxiety; I recommend working with your vet to select one of them. Your best bet will be to pick one containing B. longum (tested in dogs) and/or L. rhamnosus (tested in mice and humans), and not containing L. casei (may increase anxiety).

NO GUTS NO GLORY

Behavioral probiotics can provide a helpful adjunct to behavioral medication, as they did for my anxious dog, whose behavior noticeably improved on Calming Care. Or they can provide a mild effect in dogs who are not on medication. Remember, again, that dogs with serious anxiety issues deserve a visit to a veterinarian who specializes in behavior to discuss medication, as probiotics alone won’t be powerful enough to give them relief.

Our understanding of how the gut microbiome influences behavior is in its infancy. Perhaps in future years we’ll be able to assess a dog’s gut microbiome, predict how it’s influencing their behavior, and tailor a specific probiotic cocktail to push them in the right direction. For now, we’re mostly wandering in the dark. 

However, probiotics are very safe to use and can be something to try when you’re looking for a supplement to help blunt your dog’s anxiety. 

Jessica Hekman, DVM, Ph.D., is a researcher at the Karlsson Lab at the Eli and Edythe L. Broad Institute of MIT and Harvard, studying the genetics of canine behavior. She also teaches online webinars and courses about canine genetics.