Gut feeling. Gut check. Trusting one’s gut. Colloquialisms hint at the latent wisdom lurking in our small and large intestines, but for centuries, our understanding of how mind and gut are linked was more folkloric wisdom than evidence-based knowledge.

This is changing. While much about the gut-brain axis remains shrouded in mystery, a June 2022 study published in Translational Psychiatry provides a fascinating glimpse of how the gut’s multitudinous microbes may affect our mental health.

Schaub AC, Schneider E, Vazquez-Castellanos JF, et al. Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial. Transl Psychiatry. 2022;12(1):227.

 

 

The brain-gut axis

The results added to the growing mass of evidence suggesting that gut health is linked with mental health.

One of the lead researchers behind this study was Else Schneider, PhD, a psychologist and senior researcher at the University of Basel in Switzerland. She said that among the study’s findings, the most surprising one was the breadth of the intervention’s impact.

“What I was fascinated about was that we found changes between the (study and control) groups on all levels: on the gut, on the brain, on the behavior,” she said.

And these results weren’t fleeting, she added. Four weeks after the intervention, the team re-assed gut microbiota and behavior.

We still found some stable effects, especially for the depressive symptoms. And that’s  something I didn’t expect to see.

While the findings are illuminating, the study itself was also pioneering.

 

Inside the study

This research is the first effort to determine if high-dose probiotic supplements, administered over a short interval, can limit depressive symptoms, affect the gut microbiome, and produce neural changes in patients with depression.

Study participants received either a probiotic supplement or placebo for 31 days, in addition to their usual treatment. Among the participants, 21 received a probiotic and 26 a placebo.

Participants completed the Hamilton Rating Scale for Depression before and after intervention, as well as a brain imaging and gut microbiota analysis. Researchers repeated this battery without brain imaging 4 weeks after the study concluded.

The intervention group also experienced an increase in gut levels of Lactobacillus, as well as neural changes documented by imaging.

 

A look at the imaging

Schneider found the imaging portion of the story particularly revelatory. Participants were shown pictures of fearful, semi-fearful, and neutral faces and researchers used imaging to assess the functional response in the brain in the form of putamen activation.

The team expected to see the greatest changes with the fearful faces, such that participants would perceive them as less fearful. According to Schneider, the neutral faces elicited the most change whereas there was no difference between the probiotic and placebo group when participants viewed the fearful faces. Schneider attributed it to the negativity bias linked with depression.

Neutral faces are not perceived as neutral faces.

“Depressed patients perceive them as more sad or fearful, whereas health patients or health controls tend to perceive neutral faces as happy faces,” she added.

Those negativity bias improvements may leave you wondering which probiotic to use with your patients.

 

Putting it into practice

The study probiotic was not a specialty concoction, but a brand widely available in Swiss drugstores: Vivomixx. Each dose contains 900 billion colony-forming units of eight different strains:

• Streptococcus thermophilus

• Bifidobacterium breve

• Bifidobacterium longum

• Bifidobacterium infantis

• Lactobacillus acidophilus

• Lactobacillus plantarum

• Lactobacillus paracasei

• Lactobacillus delbrueckii subsp. Bulgaricus

The study did not determine which strain or strains were responsible for improvement, so clinicians looking to replicate these findings likely should select probiotics containing these strains.

“Unfortunately, at this moment, we don’t have any idea which specific bacteria are important for the improvement of depressive symptoms,” Schnedier said, which is why the research team selected a product with a wide range of bacteria.

Also, Schneider noted that just as with antidepressants, adherence is critical for probiotic add-on therapy. Failing to take probiotics over a specific time period will fail to remodel the microbiota. In the study, participants took the probiotic twice daily, mixed into a cold, non carbonated drink.

 

Looking ahead

While the study clearly illustrates the efficacy of probiotics as an add-on therapy for MDD, it also raises a number of questions, which will need to be answered by future studies. For example, why did the probiotics lead to a gut resurgence of Lactobacillus, specifically? Which microbe, or combination of microbes, is improving symptoms? And what is the mechanism of that enhancement?

“I think that’s the fascinating stuff about probiotics,” Schneider said. “They don’t do harm, or a lot of harm, but they are also more like a holistic treatment. Different symptoms are improved by probiotic supplementation.”