Undoubtedly, the gut microbiome has emerged as a key influencer of countless human biological processes. Our resident bacteria, viruses, fungi, and archaea colonise virtually all body sites and play pivotal roles in immunity, energy metabolism, and gastrointestinal health. Their influence even extends to the brain, affecting cognitive processes and mental wellbeing. The question is, could we improve brain functioning and behaviour by shifting the landscape of the microbiome?
Before delving into the detail, we need to appreciate the microbiome-gut-brain axis, the bidirectional communication between the microbiome and the brain. The power of this communication system is best exemplified in animal studies. Mice that are microbiome-depleted through antibiotic therapy or raised as microbiome-devoid in sterile cages and conditions, exhibit a range of behavioural deficits. Strikingly, recolonisation with normal microbiota helps to counteract these deficits.
Adding to the knowledge we have from animal studies, the composition of the human microbiome in certain psychiatric and neurodevelopmental disorders (such as anxiety, depression, and autism spectrum disorder), differs to that in healthy individuals. Although establishing a specific disease-associated microbiome is difficult, the microbiome in individuals with these disorders is often characterised by lower abundances of beneficial microbes (eg, butyrate-producing Faecalibacterium) than in healthy individuals. This research has opened up a range of opportunities for the development and testing of a class of novel microbiome-targeted therapies (including a host of so-called iotics [prebiotics, synbiotics, postbiotics], faecal microbial transplants, and even diet) that reconfigure the microbiome to a more preferential profile, with benefits for the brain. These therapies are termed psychobiotics. Psychobiotics are an exciting proposition, particularly for conditions such as depression, which has been increasing in prevalence, particularly since the COVID-19 pandemic, and for which there has been very few drug discoveries for many years.
So, what is the right psychobiotic for improving our brain health or for specific psychiatric conditions like depression? Sadly, we are still some way from formulating specific recommendations. Psychobiotic research is still very much in its infancy.
The most promising area for the use of psychobiotics thus far is for the treatment of depressive symptoms. Meta-analyses indicate that administration of probiotic organisms (mostly Lactobacillus and Bifidobacterium strains, alone or in combination) for a period of several weeks reduces the severity of depressive symptoms compared with placebo. Perhaps even more fascinating is that changing your diet can improve your mood. Specifically, data from three randomised controlled trials show a Mediterranean-style diet can have an antidepressant effect in people with elevated depressive symptoms in conjunction with their usual antidepressant medication. The Mediterranean diet, a traditional, largely plant-based diet, is rich in nutrients such as fibre and polyphenols that can influence the microbiome. Emerging evidence demonstrates this specific dietary pattern can lead to beneficial microbiome shifts, including increased abundance of health-promoting microbes (eg, F prausnitzii, Bifidobacterium spp). It is thought that microbiome modulation is an important conduit by which diet benefits the brain.
Several issues need to be considered in the interpretation of psychobiotic research. First, many trials of psychobiotics include patients with co-occurring chronic conditions, some of which also benefit from microbiome-targeted therapy, which can confound findings. Second, a myriad of tools are used to measure psychiatric symptoms, including both self-report and clinician-centred evaluations, which limits the ease of summarising the evidence. Finally, with regard to probiotic interventions, the heterogeneity of product types and doses studied currently limits our ability to make solid conclusions.
The concept of psychobiotics is relatively new but major efforts are underway to test a realm of therapies for their psychobiotic potential across a multitude of psychiatric conditions. For example, probiotic studies in autism and fermented food trials in depression are underway. An added complexity to the implementation of psychobiotics in practice is the variable microbiome response to these sorts of interventions, meaning psychobiotic therapy might need to be personalised. There is hope that specific recommendations for psychobiotic dosing and duration will become available and eventually be integrated into clinical guidelines. These therapies are safe, low cost, and less invasive than some traditional treatments for psychiatric disorders. Our ability to modify the microbiota through our own doing is of appeal, especially to patients who are resistant or not responsive to standard treatments. Future trials and good science will shed light on whether the excitement is justified.
For more on depression and COVID-19 see Seminar Lancet 2021; 398: 1700–12
For more on psychobiotics see Biol Psych 2013; 74: 720–26, Neurosci Biobehav Rev 2019; 102: 13–23, Adv Nutr 2021; 12: 1239–85, and Psychosom Med 2019; 81: 265–80
KB has recently finished a post-doctoral fellowship at the APC Microbiome Ireland, Cork, Ireland. HMS is based at the Food & Mood Centre, IMPACT Institute, School of Medicine, Deakin University, Geelong, VIC, Australia
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