Gut-brain axis: Scientists call for rigorous research to validate promising probiotic effects

Although researchers found promising results of probiotics’ effects on mental well-being through the gut, they call for rigorous, longitudinal research to “clarify the beneficial effects of probiotics on the gut-brain axis and mental health.” In their review of randomized controlled trials using functional MRI methodologies, they observe methodological variability and limited sample sizes. 

Task-based functional MRI studies on healthy individuals indicate that probiotics modulate brain activity related to emotional regulation and cognitive processing. Studies also suggest that probiotics could normalize brain function in patients with major depressive disorder and irritable bowel syndrome (IBS). 

Meanwhile, resting-state functional MRI research reveals changes in connectivity patterns and suggests improved connectivity in mood-regulating networks. 

Nutrition Insight discusses the study’s outcomes and implications for future research with its first author, Annachiara Crocetta, a Ph.D. student at the University of Turin, Italy, and a research member of the university’s Functional Neuroimaging and Complex Neural Systems Laboratory. 

“The level of evidence provided by our study is probably far from directly influencing the biotic industry. However, we hope this could suggest the value of considering probiotics to improve cognitive and emotional well-being, not only as a consequent effect of acting on digestive health.”

She adds that the study highlights evidence linking probiotics to brain function, mainly through the gut-brain axis. “One significant impact we hope the study has is encouraging more interdisciplinary research, bringing together fields like microbiology, neuroimaging and psychology to explore how gut health affects brain function.” 

Neuroimaging results

The review, published in Frontiers in Nutrition, identifies studies investigating probiotic effects on brain activity in healthy individuals and clinical populations, such as people with major depressive disorder and IBS. The team included 12 studies and 24 reports on the included studies.

The authors detail that neuroimaging techniques, such as functional MRIs, provide an “objective and detailed method for observing brain activity in response to probiotic intake.” 

These methods detect changes in blood oxygen levels, which correlate with neural activity. This allows researchers to visualize and measure brain function in real-time. They examine different aspects and address the limitations of relying on questionnaires to study probiotic effects. 

“The collected evidence suggests that probiotics have a notable impact on functional connectivity with implications for both general cognitive functions and specific psychiatric conditions,” conclude the authors. 

However, Crocetta underscores that while these are promising results, the field is in its early stages. 

“The variability in findings across studies suggests that more precise methodologies and better-controlled trials are needed to fully understand how probiotics affect brain health. Nonetheless, the potential exists, and as research advances, probiotics may become a common supplementary treatment in both gastrointestinal and mental health care.”

Neuroimaging techniques, such as functional MRIs, can provide an objective and detailed method to measure gut-brain effects.Addressing research gaps

The authors detail several constraints in their review, such as the limited number of studies examining the impact of probiotics on brain functioning. They state that this restricts the ability to draw robust conclusions and completely understand probiotics’ influence on neuronal activity. 

Research exclusively examines patients with major depressive disorder and IBS, which the authors say makes it difficult to replicate findings. This is a critical step in confirming results and establishing a “reliable foundation for clinical applications.” 

“Our review emphasizes the need for more rigorous studies, which should include larger sample sizes, well-defined probiotic strains and consistent dosages,” details Crocetta. 

“Future studies should also aim for longer intervention to assess the sustained impact of probiotics on brain function, rather than just short-term changes. For instance, longitudinal studies that track participants’ mental health and brain function over months or years would provide deeper insights.” 

She also points to the need to include a more diverse range of participants regarding age, gender and health status to ensure that findings are applicable across populations. 

“A further pivotal point is the control of possible interacting and confounding factors. The main reason for this is diet, as the intake of different foods could dramatically impact the effect of probiotics. In clinical studies, this would mean, for example, controlling for interactions between probiotics and dietary variations.”

Crucial collaboration in complex research

Crocetta notes that the gut-brain axis is a “relatively new and complex field of research,” which could explain the limited number of studies. 

“While there is strong evidence that probiotics influence gut health, connecting these changes to brain function requires advanced neuroimaging techniques, such as functional MRI, which need significant resources and expertise.” 

Crocetta calls for more collaboration between research departments to link probiotics to brain health.“Many researchers primarily focused on probiotics and microbiota may not have access to this level of expertise or equipment,” she explains. “The other way around, neuroscience research centers usually miss the possibility of analyzing microbiota samples, underlining the need for more collaborative, interdisciplinary work. Moreover, the variability in probiotic strains and the difficulty in standardizing trials adds to the challenge.” 

Crocetta and her colleagues expect that the number of studies will increase as the field grows, “especially as more researchers appreciate the potential of probiotics to influence not only gastrointestinal health but also cognitive and emotional well-being.”

Market developments

The nutrition industry is continuously developing products targeting the gut-brain axis and exploring other links, such as the gut-heart, gut-muscle or gut-skin axis. For example, Innova Market Insights data suggests that supplement launches supporting the gut-brain axis increased by 25% CAGR between April 2019 and March 2024.

Moreover, companies collaborate with research institutes to develop biotics backed by science. This year, Kerry announced a partnership with microbiome research center APC Microbiome Ireland to explore innovative gut-brain axis solutions. 

Crocetta notes that the review offers new opportunities for companies to “design probiotics specifically formulated to target the gut-brain axis.” 

“By identifying strains that have demonstrated benefits for brain function — such as modulating areas involved in emotional regulation and stress — companies can create more specialized products.” 

She predicts: “In the far future, this could also lead to the development of personalized probiotics, starting from individualized analyses of the microbiome composition and cognitive indexes.”