Psychobiotics: What Do We Know and Where Do We Go?

Can supplementing the diet with probiotic (beneficial) bacteria affect psychological outcomes? The authors of a review recently published in Trends in Neurosciences discuss the current knowledge of psychobiotics (probiotics that affect gut-brain signaling) and identify outstanding questions for future research. Although the authors are optimistic about the therapeutic potential of psychobiotics, they caution that research to date has provided little evidence that psychobiotic supplements provide clear benefits.

Psychobiotics are “probiotics that, when ingested in appropriate quantities, yield positive psychiatric effects in psychopathology,” write the authors. In the review, the term psychobiotics encompasses both probiotics and prebiotics (substances that facilitate the growth of beneficial bacteria). The authors suggest that the definition be further expanded to include anything that exerts a microbiome-mediated effect on the brain.

Studies in rodents and humans have shown that probiotics such as bifidobacteria and lactobacilli affect emotional responses, inflammatory mediators, and neurotransmitter function. “Those studies give us confidence that gut bacteria are playing a causal role in very important biological processes, which we can then hope to exploit with psychobiotics,” said study author Philip Burnet, PhD (Department of Psychiatry, University of Oxford, United Kingdom), in a news release. “We're now on the search for mechanisms, mainly in animal models.”

Fewer studies have explored the psychophysiological functions of prebiotics. The existing prebiotic studies focus mainly on galacto-and fructooligosaccharides, nutrition sources for bifidobacteria and lactobacilli. Published reports indicate that prebiotics lower the waking cortisol response in humans and increase expression of brain-derived neurotropic factor in rats.

Although researchers have identified some of the pathways by which psychobiotics affect the brain, the mechanisms are still not fully understood, say the review authors. “A crucial step in developing knowledge of the mechanisms lies in investigating how the microbiome and the brain communicate with one another,” they write. The intestinal microbiota has previously been shown to modulate development of the enteric nervous system. The vagus nerve, satiety hormones, and the immune system (via bacterial effects on cytokines and glucocorticoids) may also be involved in communication along the gut-brain axis, the network that connects the gastrointestinal tract, enteric nervous system, and brain.

Prebiotics and probiotics are not the only substances that affect the gut-brain axis, say the authors. Antipsychotic and antibiotic medications, for example, can affect the composition of the intestinal flora, causing neurochemical effects. “We call for an even further widening of the definition of ‘psychobiotics’ to include drugs such as antidepressants and antipsychotics, and activities such as exercise and eating, because of their effects on gut bacteria,” says Burnet.

The idea of manipulating the gut microbiome to improve psychiatric outcomes is compelling, but current supporting evidence is scant. The authors of a 2015 systematic review of psychobiotics wrote that “there is very limited evidence for the efficacy of probiotic interventions in psychological outcomes,” concluding that “more trials are necessary before any inferences can be made about the efficacy of probiotics in mental health applications.”

More research into how psychobiotic substances work is needed, says Burnet. The review authors identify several topics for further investigation, including the following:

• Do psychobiotics change the composition of the gut microbiome?
• Do the effects of psychobiotics depend on the dose or the patient’s age?
• What is the time of onset of clinical effects after psychobiotic administration?
• What long-term changes do psychobiotics produce in the nervous system?
• Do psychobiotics improve cognitive performance?
• What are the adverse effects and drug interactions of psychobiotics?
• Why do different strains of probiotics cause different effects?
• Which patient characteristics and other factors moderate psychobiotic effects?

Exploring these topics could open a path for future development of psychobiotics, write the authors. For now, the health benefits of psychobiotic supplements are not clear.

​Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.