Culturing Happiness

How a century of probiotics led to the psychobiotic revolution.

“If microbes are controlling the brain, then microbes are controlling everything.” —John F. Cryan

The connection between microbes and minds has a surprisingly long and twisty history. It all started at the beginning of the 20th century, when zoologist Élie Metchnikoff became fascinated by yogurt. He found that Bulgarian peasants who consumed copious quantities of yogurt lived to a ripe old age despite their harsh living conditions. They also seemed to be happier.

Being a curious zoologist, he investigated and discovered that yogurt was teeming with Lactobacillus bacteria. Convinced that the bacteria were keeping the peasants healthy, he himself adopted the habit of eating yogurt daily. Sadly, as sometimes happens, his theories about probiotics and health were overlooked and not rediscovered until the 1990s.

Unless your gut looks like a yogurt maker, these particular microbial species are unlikely to take up permanent residence there, but they can still provide a healthy boost in transit. Today, you can pick up a jar of probiotic supplements that Metchnikoff would instantly recognize because most of them are standard yogurt bacteria, largely Lactobacillus and Bifidobacteria.

Family feuds

You might think that closely related bacteria would get along with each other and that you could just replace one with a near cousin. But that’s not how it works in the microbial world. It is tough to be tiny, and for microbes, the closer the relationship, the greater the competition.

So, identity counts. Calling bacteria Lactobacillus is about as descriptive as calling a flower a rose. Is it a tea rose, a shrub rose, or a climbing rose? What color is it? Does it have a scent? We need more specificity to truly identify both roses and microbes. Different strains of microbes produce different chemicals, and that matters—both to other microbes and the host.

The world of probiotics changed in 2013, when Ted Dinan, Catherine Stanton, and John Cryan of University College Cork announced a new type of probiotic, called a psychobiotic. Despite the somewhat sinister-sounding name, psychobiotics are defined as microbes that can boost your mood, decrease anxiety, and improve cognition. That’s a big lift for such a small creature.

[Full disclosure, I wrote a bestselling book with Cryan and Dinan titled The Psychobiotic Revolution from National Geographic]

At first, these psychobiotics could only be identified at the genus level, which is not very detailed. But the 2020s brought a new set of tools including metagenomics, which allows researchers to look at every single gene in a sample, with the ability to identify microbes down to the strain level. That has ushered in a new era of extremely well-defined psychobiotics.

Psychobiotics get real

At the top of the list, not too surprisingly, is Lactobacillus, specifically L. plantarum. Note that biologists thankfully abbreviate the genus name to save ink. Strains of this species, including JYLP-326, CR12, P72, 299v, and GM11 have been shown to be effective in alleviating symptoms of depression, anxiety, and cognitive dysfunction. L. plantarum is found naturally in various fermented foods, such as sauerkraut, capers, olives, grape juice, and wine.

Another potent psychobiotic is Bifidobacterium breve, especially the CCFM1025 strain. In clinical studies B. breve has alleviated symptoms of depression and sleep disorders. B. breve occurs naturally in dairy products and breast milk. B. longum is a related species with similar properties.

Another psychobiotic is Akkermansia muciniphila which has antidepressant effects and improves cognition. A. muciniphila loves polyphenols, which can be found in colorful foods like cranberries, grapes and berries.

L. helveticus, present in fermented milk products such as cheese and yogurt, is another strain with anxiolytic and antidepressant properties. Rounding out the Lactobacillus group is L. reuteri and L. rhamnosus strains zz-1, UBLR-58, and JB-1.

Some of these microbes provide a better environment for other microbes on the list, so they like to be paired up. Conversely, some of these may conflict and cancel out the psychobiotic effect altogether. For this reason, manufacturers try to create carefully curated blends.

Modern psychobiotics may contain a dozen or more different microbial species, often with a serving of prebiotics — microbe food. Like packing a lunch, these help the microbes survive the trip through the gut.

Caveats

Probiotics may not be for everybody. If you have a flare-up of IBS or IBD, wait until it dies down before taking supplements. Talk to your doctor. These gut disorders can be a sign of an actively leaking gut, and no matter how good a psychobiotic is in the intestines, it is a pathogen in the blood.

There have also been reports of small-intestinal bacterial overgrowth (SIBO) from probiotics, so pay attention to your health and keep notes.

Before you take probiotic or psychobiotic supplements, try the natural versions: ferments like yogurt, kimchi, kefir, kombucha, and sauerkraut. These are time-tested foods that help to balance your microbiome and keep your immune system on an even keel. Start small: these ferments can be potent.

From their humble beginnings as Bulgarian yogurt, probiotics and psychobiotics are becoming big players in the world of health, longevity, and mood. It’s humbling that such tiny creatures have such a big impact, but we can’t afford to ignore them. We may not have control over our genes and environment, but these microbes are ours to take advantage of.

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References

Dinan, Timothy G., Catherine Stanton, and John F. Cryan. “Psychobiotics: A Novel Class of Psychotropic.” Biological Psychiatry 74, no. 10 (2013): 720–26.

Coelho, Taiane, and Raquel Kerpel. “Psychobiotics in the Treatment of Depression: A New Look at Mental Health – a Systematic Search Review.” Revista Científica Multidisciplinar Núcleo Do Conhecimento, May 7, 2022, 125–52.

Mosquera, Freiser Eceomo Cruz, Santiago Lizcano Martinez, and Yamil Liscano. “Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials.” Nutrients 16, no. 9 (2024).