The review — published in Cell — discusses the most effective ways of implanting brain-altering bacteria in the gut to provide mental benefits.
The challenge in directing communication methods or mechanisms of action is compounded by the difficulty in interpreting results from human studies.
Brain-related reactions such as mood in response to probiotics are mainly self-reported, but physiological changes, such as reduced cortical levels and inflammation, have also been recorded.
While the review recognises the possibilities these supplements have as ‘add-on’ therapies for antidepressants or antipsychotics, more questions need to be answered about what strains of bacteria offer specific benefits, how they work, whether they offset other benefits, and how they will be regulated.
"Psychobiotics are a long way from their true translational potential. It's a little boring to say that we need more studies, but that is always the case in any academic discipline," said lead author Dr Philip Burnet, an associate professor of psychiatry at the University of Oxford.
"The technology and resources already exist for such investigations, so though we are enthusiastic, the enthusiasm needs to be tempered and channelled toward answering the core mechanistic questions."
Dr Burnet said the term ‘psychobiotics’ could even be extended.
"Prebiotics are another channel to alter gut bacteria," he said. "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."
Psychobiotic research gained momentum after a pivotal study that found germ-free mice reacted poorly to stress compared to normal controls. The abnormal reactions were reversible through probiotic-induced bacterial recolonisation.
"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 Dr Burnet.
"We're now on the search for mechanisms, mainly in animal models. The human studies are provocative and exciting, but ultimately, most have small sample sizes, so their replicability is difficult to estimate at present. We're 'cautiously optimistic.'"
Boosting brain function
It is generally accepted that the bacteria-gut-brain axis consists of the nervous system of the intestines, the immune system, the vagus nerve, and possibly gut hormones and neurotransmitters.
As well as neurological disorders, psychobiotics have been implicated in enhancing cognitive function.
One mice study demonstrated that psychobiotics can increase brain-derived neurotrophic factor (BDNF), which is closely linked to learning and memory.
A recent systematic review of psychiatric benefits of probiotics in humans found little evidence of positive outcomes.
“Numerous limitations must both constrain enthusiasm and stimulate further investigations,” the review concluded. “Many studies examine several psychophysiological variables, of which only a few register effects. While exciting, issues of false-positives and false-negatives have not been adequately investigated.”
Published online ahead of print, doi.org/10.1016/j.tins.2016.09.002
“Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals.”
Authors: Philip Burnet et al