Category: Drugs

A new review and analysis of several studies has found that probiotics do not improve self-reported anxiety symptoms in humans, although there was evidence of minor improvements in rodents.

The study reviewed 36 preclinical studies in total, 14 involving humans and 22 involving rats and mice. That’s a decent-sized sampling of the research covering a variety of probiotic strains, and it turned up zero evidence that humans with self-reported anxiety symptoms benefited from taking any of them.

“Probiotics did not significantly reduce symptoms of anxiety in humans and did not differentially affect clinical and healthy human samples,” the study concluded.

One of the strains, Lactobacillus (L.) rhamnosus, did appear to reduce anxiety symptoms in rodents, but further analysis showed that effects were most pronounced only for the sickest of the specimens, and even in those animals the results weren’t dramatic.

Probiotics are one of the strongest selling nutritional products in the world, with annual US sales exceeding $3.3 billion in 2016. That market size is predicted to more than double by 2025. Clearly a large chunk of the supplement-buying public has confidence in these products, and the marketing push is only intensifying. But this study, like others turning up similar findings, suggests caution is warranted.

“I think people should wait — that’s the best takeaway here,” said lead study author Daniel J. Reis, a doctoral student of clinical psychology at the University of Kansas. “We’re in the early days of this research into probiotics. I’ve seen a lot of stories hyping probiotics as helpful for anxiety. We’re not saying they do nothing, but we have a lot to figure out before we know if they can be used therapeutically.”

Why some effects were found in rodents and not in humans isn’t clear, but the researchers noted that the differences in dosage between humans and rodents were significant.

“If you control for the weights of animals versus humans, animals are getting much larger doses of probiotics in these experiments by one or two orders of magnitude. Sometimes the doses were hundreds of times higher than we see in human studies,” said Reis in a press statment.

The researchers also noted that while this study didn’t find anxiety-reducing benefits for humans, it’s still possible that a pathway exists for certain strains to yield therapeutic effects. And they were clear that the anxiety levels among the human participants in the reviewed studies weren’t necessarily “clinically elevated.” Future research has an opportunity to delve more deeply among that expanding population.

“We see a lot of pathways between our digestive systems and our brains,” Reis said. “We see nervous system connections, the inflammation response — these microorganisms seem to be able to influence the human brain through this gut-brain axis. We wanted to know if changes to the microbiota could improve mental health. But in terms of research, it’s all at a very preliminary stage.”

And that, for the moment, is the big takeaway on probiotics – the research is still very preliminary, despite marketing claims of conclusive results. Evidence supporting the claims just isn’t there, at least not yet.

Scientific research is nearing a consensus that bacteria in our digestive systems affect our brains. The microbiome in our guts, populated by billions of bacteria, appears to play a significant role not only in our digestive health, but also our mental health. Exactly how this happens is still being worked out, with each new study turning over another proverbial rock of possibilities. Despite these advances, we don’t yet know how, or if, probiotic supplements can improve our mental health by influencing gut bacteria. The marketing of these products is far ahead of the facts, as a quick review of what we know will show.

First, a brief sampling of the latest bacteria-brain research, which includes a study that found specific hormonal exchanges enabling communication between gut bacteria and the brain. This is especially noteworthy because the hormone in question is cortisol, the so-called “stress hormone”– a well-established indicator of stress levels in humans and other mammals. The study was conducted in pigs, which share several physiological similarities with humans, and it identified a possible communication pathway between gut bacteria and the brain that uses cortisol as a channel to send “messages.” The implications of this research will take some time to unravel, but one initial takeaway is that our stress-response system may play a key role in how gut bacteria communicate with the brain.

Another recent study suggests that gut bacteria may influence anxiety and depression. This study was conducted with mice raised in a sterile, germ-free environment devoid of bacterial influence. Researchers exposed these mice to gut bacteria and watched what happened compared to mice that were raised in a normal, germy environment.  The germ-free mice exposed to bacteria developed anxiety and depression symptoms on par with the human equivalent. The researchers identified a specific brain region influenced by the bacteria, and suspect that our early-life exposure to bacteria may predispose us one way or another to anxiety and depression later on. Again, the conclusions are speculative, but the research is exciting because it moves us a little closer to figuring out what’s going on.

More studies like these are underway and another wave is in the planning phase. So why, with all of this research, can’t we make grand claims for the promise of probiotics? After all, if we have even an inkling that gut bacteria affect our brains (and we certainly have more than an inkling at this point) then why not jump onboard the probiotic supplement express?

The reasons can be boiled down to a few big ones.

The probiotic philosophy is to blast the gut with billions of allegedly “good” bacteria, in hopes of populating out the bad ones. While re-populating the gut with good bacteria sounds plausible, there’s little scientific clarity around which gut bacteria are objectively “good” or if that qualification is even valid. Bacteria can be “good” or “bad” depending on a slew of variables. Even less clear is which bacteria influence the brain and how they’re exerting their influence.

But let’s say we could achieve perfect clarity on that point, there’s still an enormous gastric obstacle ahead. Whether you’re ingesting a probiotic with one billion or 30 billion live bacterial cultures, they still have to survive your stomach acid to do anything worthwhile. Only a couple types of bacteria have proven resistant enough to survive that peril (lactobacillus and bifidobacteria), which means almost everything else in your pricey probiotic capsule is toast.

But let’s say that problem is solved by a fantastic pill coating – what will this army of bacteria do once they arrive in your gut?  We simply don’t know enough to know for sure. Last year a review of probiotic trials in humans concluded that the research “demonstrates a lack of evidence for an impact of probiotics on fecal microbiota composition in healthy adults.” In other words, we don’t know precisely what probiotics are doing in the gut – and there’s at least a possibility that they aren’t doing much to make a difference.

Given how little we understand about what probiotics can accomplish in our guts, jumping to a further conclusion that they can improve our mental health is really reaching. That hasn’t stopped those marketing these products from making outlandish claims, but that’s standard operating procedure for a large chunk of supplement marketing.

Where actual science is concerned, we don’t yet know if probiotics can achieve the promises made for them, or what sort of probiotic formula will prove effective. We may eventually find out that probiotics need to be tailored to a given person’s microbiome like bespoke clothing. Once that’s established (if it can be established), then perhaps we’ll have a better opportunity to understand how probiotics might improve our mental health – assuming the underlying theory holds up over time.

Right now, we don’t know enough to justify the claims made for probiotic supplements. The marketing is leagues ahead of the evidence, and we’d do well to view these claims with skepticism. Perhaps one day probiotics will give our brains a boost, but we’re just not there yet.

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