Probiotic supplements may improve working memory

A new study published in Nutritional Neuroscience examined how probiotic supplements, a prebiotic-rich diet, or their combination (synbiotic treatment) impact cognitive function in adults with low mood and dietary improvement potential. The randomized controlled trial provides tentative evidence that probiotic supplementation might improve working memory. However, the findings are preliminary, and the researchers emphasize the need for larger studies to confirm these effects.

In recent years, there has been increasing interest in the gut-brain axis and its potential link to cognitive performance. The gut-brain axis is a complex, two-way communication system between the digestive system and the brain, mediated through neural, hormonal, and immune pathways.

At the center of this connection is the gut microbiota—trillions of microorganisms residing in the digestive tract—that play a key role in influencing brain function and behavior. These microbes produce various metabolites, such as short-chain fatty acids and neurotransmitters, which can regulate inflammation, impact mood, and affect cognitive processes like memory and attention.

One way to influence the gut microbiota is through probiotics, which are live microorganisms that provide health benefits when consumed in adequate amounts. Commonly delivered through supplements or fermented foods like yogurt and kefir, probiotics can help restore balance to the gut microbiota, enhance the production of beneficial metabolites, and reduce inflammation.

Some studies suggest that probiotics may improve cognitive function, particularly under stress or in clinical populations, by targeting pathways related to mood and brain health. However, the evidence remains inconsistent, with other studies reporting little or no cognitive improvements from probiotic use.

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In addition to probiotics, prebiotics—non-digestible dietary fibers that serve as food for beneficial gut bacteria—have also been explored for their impact on the gut-brain axis. Found naturally in foods like whole grains, vegetables, fruits, nuts, and legumes, prebiotics encourage the growth and activity of healthy gut bacteria, leading to the production of compounds such as short-chain fatty acids that support brain function.

While prebiotic supplements have shown promise in improving aspects of cognition and mood, much of the research has relied on isolated supplements rather than whole-diet approaches. This distinction is important because diets rich in prebiotic foods may offer broader and more sustainable benefits for gut health.

To better understand whether gut-focused interventions could yield measurable improvements in mental health, the researchers behind the new study designed an 8-week randomized controlled trial to compare probiotic supplementation, a prebiotic-rich diet, and their combination in adults with low mood and room for dietary improvement.

“We were inspired by the SMILES trial, which was the first RCT to demonstrate the strong potential for diet to improve symptoms of depression. Around the same time, we noted a growing body of literature on the impact of probiotic and prebiotic supplements on mental health, providing evidence for the involvement of the gut-brain axis,” said study author Tanya Freijy, a PhD candidate at the Florey Institute of Neuroscience and Mental Health at The University of Melbourne, Australia.

“Yet, there was a gap in whole-diet approaches to improving gut health, and thereby potentially, mental health. We consulted with Professor Jane Muir, one of the lead researchers behind Monash University’s High Fibre, High Prebiotic Diet, and adapted this diet for use in our study.”

The study included 118 adults aged 18 to 65 who reported moderate psychological distress and consumed low amounts of prebiotic fiber in their daily diets. To participate, individuals had to meet specific health criteria, including avoiding probiotic supplements and fermented foods before the trial. Exclusion factors included gastrointestinal conditions, psychiatric disorders, pregnancy, or use of certain medications.

The participants were randomly assigned to one of four groups:

1. Probiotic group: Received probiotic supplements while maintaining their usual diet.
2. Prebiotic diet group: Followed a prebiotic-rich diet and received placebo capsules.
3. Synbiotic group: Received both the probiotic supplements and the high-prebiotic diet.
4. Placebo group: Took placebo capsules and continued their regular diet.

At the start and end of the trial, participants completed cognitive assessments using the Cogstate Brief Battery, a computerized test that measures processing speed, attention, visual learning, and working memory. Performance was evaluated based on reaction time and accuracy.

Probiotic supplementation appeared to have the most promising, albeit modest, effect. The results suggested a potential improvement in working memory, one of the core cognitive functions involved in holding and manipulating information over short periods. Participants in the probiotic group demonstrated a small improvement compared to the placebo group.

“However, the evidence remains inconclusive until replicated in larger studies, ideally with more complex measures of cognition,” Freijy told PsyPost.

In contrast, the prebiotic-rich diet showed weak evidence of impairing processing speed, which measures how quickly and accurately participants can respond to simple tasks. The prebiotic group performed slightly worse than the placebo group. However, the researchers caution that this finding may have been a statistical anomaly rather than a true negative effect, as no prior studies have reported cognitive impairments from prebiotics.

“The prebiotic-induced impairment in processing speed was unexpected and inconsistent with the positive effects the same dietary intervention had on mood, anxiety, sleep, and perceived stress in our previous publication,” Freijy explained. “Closer examination of the data indicates that this finding is most likely due to chance.”

When looking at the synbiotic group, which combined probiotic supplementation with the prebiotic-rich diet, there was no clear evidence of a synergistic or additive effect. In other words, combining the two interventions did not produce stronger cognitive outcomes than either treatment alone. The results indicated that the effects of the probiotic and prebiotic interventions, if present, were independent and did not interact significantly.

“Another unexpected finding was the lack of cognitive benefit from the synbiotic treatment (high-prebiotic diet plus probiotic supplement), contrary to our expectation that it would outperform the other interventions,” Freijy said.

The researchers noted that several limitations that may have influenced the findings. For instance, the sample size was relatively small, and the study was not specifically designed to measure cognitive effects. In addition, the participants were generally healthy, non-clinical adults, so cognitive performance may have been close to its natural ceiling. This could limit the scope for detecting improvements.

Despite these challenges, the researchers remain optimistic about the broader implications of their work. “We hope to link our microbiome analysis from this project (currently in preparation) with the changes we observed in mental health and cognition,” Freijy told PsyPost. “We look forward to publishing the microbiome findings in future. We also have a goal to publish further detail about our high prebiotic dietary protocol and feasibility of the diet for the benefit of future research and potentially clinical practice.”

“This study is one component of our larger gut-brain project, the Gut Feelings trial. Our primary publication on the mental health effects of our clinical trial is freely available online. We recommend The Food and Mood Centre, Deakin University, as a resource for learning about the field of nutritional psychiatry and the latest research being conducted on nutrition-based approaches to preventing and treating mental disorders.”

The study, “The impact of a prebiotic-rich diet and/or probiotic supplements on human cognition: Secondary outcomes from the ‘Gut Feelings’ randomised controlled trial,” was authored by Tanya M. Freijy, Lachlan Cribb, Georgina Oliver, Najwa-Joelle Metri, Rachelle S. Opie, Felice N. Jacka, Jason A. Hawrelak, Julia J. Rucklidge, Chee H. Ng, and Jerome Sarris.