Microbiome gut brain axis and the rise of psychobiotics

The microbiome refers to the microorganisms (or microbes) that inhabit an environment such as the human body, soil, or the ocean. An often told fact is that we are more microbe than human, as indeed we contain more microbial cells in our body than we do human cells. One of the main residences of these microbes is in our gut, which contains approximately 1000 different species of bacteria. Our microbiome, also present in our skin, lungs, and throughout the body, plays an essential role in maintaining our metabolism, digestion, and immune system. The diversity and variation in composition of the human gut microbiome can influence certain diseases such as cancer, obesity, or inflammatory bowel disease. Study of the microbiome represents an intense area of research. An online search for ‘microbiome’ in the database of EU funded projects returns 269 hits and the European Research Council has funded more than 150 projects on various aspects of the microbiome to date.

Food, microbes, and mental health

The gut-brain axis is a fascinating phenomenon describing the communication lines that exist between our guts and our brains, and vice versa. Perhaps this is unsurprising when one considers how when we are anxious, symptoms like nausea can occur. When we are heartbroken, we lose our appetite. Or, on the other hand, after a big meal we may become sleepy. However, what has been discovered is that our bacteria are often responsible for many of the conversations occurring between our gut and our brain.

Dr Ruairi Robertson, Wellcome Trust Fellow at Queen Mary University of London: “The vast ecosystem of microbes in the intestine hugely influence the messages that are sent from the gut to the brain. They do this by producing thousands of different chemicals on a constant basis which are either transported directly to the brain through the bloodstream, or which influence gut brain signalling through communication with gut cells and the enteric nervous system. One of these groups of chemicals produced by gut bacteria are neurotransmitters (such as serotonin), which are typically produced in the brain, and which influence brain function and mood.”

Another way our gut bacteria can influence our health is through their involvement in our immune systems. Dr Robertson explains, “Gut bacteria play an important role in the immune response as a huge proportion of the human immune system is based in the intestinal tract. An overload of disease-causing bacteria in the gut can trigger inflammation through the body. Many mental health disorders are associated with inflammation which potentially could be derived from the gut.”

So can we eat our way happy? How does what we eat affect our mood? And how does our diet influence our microbiome?

Dr Jason Martin, Senior Postdoctoral Fellow at APC Microbiome Ireland, University College Cork: “Dietary patterns in Western society and elsewhere throughout the world have undergone major compositional changes, in recent decades, with the intake of red meat, high fat foods, and refined sugars vastly increased. This “Westernisation” of diets results in dysbiosis (also named dysbacteriosis) a term for a microbial imbalance or maladaptation on or inside the body (i.e. an impaired microbiota) that may at least in part contribute to the increasing incidence of stress-associated chronic inflammatory disorders, such as depression and anxiety.”

Dr Martin explains that the ‘Mediterranean diet’ is not only recognised by the World Health Organisation for reducing cardiovascular disease risk, but may also be very gut friendly. Essentially, the Mediterranean diet consists of a limited intake of red meat and processed foods, and plenty of “fresh vegetables, fruits, whole grains, nuts and seeds and healthy fats (e.g. olive oil), along with a regular intake of fish, beans, eggs, poultry and fermented foods.” Dr Martin continues, “Excitingly, the Mediterranean diet appears optimal from a mental health perspective. It is associated with lower rates of depression and appears to optimally impact on the gut microbiota with preliminary evidence indicating that such a diet may have antidepressant effects that have many positive benefits for stress-related psychiatric illnesses. Simply, truly good food does lead to a good mood.”

Psychobiotics – the new anti-depressant?

Recent research has given rise to the concept of psychobiotics. There is a hypothesis that providing someone with the right cocktail of prebiotics (dietary fibre supplements that encourage bacterial growth) and probiotics (live bacterial supplements) can encourage the growth of certain healthy bacterial populations, which can affect our mental wellbeing. Perhaps, one day, these concoctions may alleviate symptoms associated with depression and other mental health issues.

Although there is now wide acceptance of a link between the gut microbiome and anxiety and depression, there is still a long way to go in deciphering mechanisms and creating treatments. One of the leading institutions in this field is APC Microbiome Ireland SFI Research Centre at University College Cork, Ireland.

Dr Jason Martin, now working at APC, says “One notable study conducted [at APC] was a study showing that depressed patients had elevated cortisol output together with decreased faecal microbial richness. […] This study provided a breakthrough moment by providing compelling evidence for a role of the brain in regulating gut microbiome. Further, this study provided evidence that some psychiatric disorders, such as depression, have an association with a gut microbial imbalance that influences both mood and cognitive function.”

Sensible optimism

Against the backdrop of this positive research progress, it is important not to get carried away. Indeed Dr Robertson notes, “The hype and hope surrounding the microbiome has begun outpacing the scientific reality. This hype leads to unscientific claims being spread on the internet and products on the market that claim to benefit the gut-brain axis but have no scientific basis. All of this hinders scientific progress as it leads to confusion for the general public and mistrust in the scientific method. It is essential that scientists continue to communicate the potential of the gut-brain axis whilst simultaneously communicating the current limitations to its clinical applicability.”

Dr Martin also cautions, “it must be noted that a recent systematic review of the psychiatric benefits of probiotics in humans found little evidence of positive outcomes. While this finding can be taken as in opposition to general optimism, it does highlight that more research is needed to better understand and rigorously elucidate mechanisms that underpin the benefits of psychobiotics.”

Diet, exercise, and the microbiome all affect our mood and wellbeing. Dr Martin notes that “differentiating the strength of effect of these subcomponents of a healthy lifestyle will help us better understand the interaction that exists both in the gut-brain-axis as well as in the human body as a system.”

Future research may lead one day to psychobiotics becoming part of a regimen to combat brain and mental health disorders, but for now, we can at least appreciate the hard work our gut microbes do to take care of us, and eat a healthy Mediterranean diet (which includes a glass of red wine!).

Useful links:
• APC Microbiome Ireland SFI Research Centre
• Microb-Predic : Microbiome-based individual biomarkers and predictors of health, cirrhosis, ACLF and treatment response
• MicrobiomeSupport will contribute to strengthening a sustainable European bioeconomy and support the European food system transformation
• MASTER – Microbiome Applications for Sustainable food systems through Technologies and EnteRprise