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Cambridge University Science Magazine
‘IF MICROBES ARE CONTROLLING the brain, then microbes are controlling everything’ said John F. Cryan, Chair of Anatomy and Neuroscience at University College Cork, Ireland. These words couldn't be more accurate in describing the critical impact that the community of microbes residing in the gut has on our adaptation and survival. It is not an exaggeration to say that we are seriously outnumbered by these microbes. The human gastrointestinal tract (the gut) alone is home to over a trillion microorganisms, collectively known as the ‘gut microbiota’, ten times more than the number of cells in the human body. It plays a vital role in metabolic processes and mental health via the gut-brain axis and regulating neurotransmitter production and the immune system.

The impact of mental health disorders goes beyond the individual affected to reach families, communities and the economy, resulting in reduced productivity, increased healthcare costs and loss of income. They are also associated with increased risk of physical health problems such as cardiovascular disease. Furthermore, stigma surrounding mental health disorders is still a major issue, which can lead to delayed diagnosis and treatment. This highlights the importance of early intervention, increased awareness and access to mental health services. It is imperative that we continue to invest in research, education and advocacy to improve the quality of life for those affected by mental health disorders.

The gut-brain axis is an exciting and rapidly-developing area of research that has the potential to revolutionize our understanding of mental health and wellbeing. The intricate connection between our gut and our brain is mediated by the gut microbiota. Demonstrated in a groundbreaking 2004 study by Sudo et al.,the gut-brain axis is a two-way communication system, with chemical signals traveling from the gut to the brain and vice versa. One of the key ways that the gut microbiota can influence the brain is through the production of neurotransmitters such as serotonin, dopamine and GABA. These powerful chemicals can modulate mood, behavior, and cognition, and they play a critical role in the development and progression of mental health disorders.

In recent years, an abundance of research has emerged linking microbial communities to various neuropsychiatric disorders, such as autism spectrum disorder, schizophrenia, depression, anxiety, Parkinson's disease, Alzheimer's disease and multiple sclerosis. While the relationship between gut microbiology and mental health has long been recognized, advances in DNA sequencing technologies and germ-free rodent models have greatly improved our ability to characterize the gut microbiome and explore its interaction with host physiology. Clinical studies have provided evidence that the gut microbiome plays a significant role in brain physiology, with growing interest in how this can aid effective clinical care, particularly in predicting responses to therapy.

By better understanding the complex interactions between our gut microbiota and our brain, we may be able to develop more targeted and effective interventions for these debilitating conditions. The Human Microbiome Project (HMP) was a multi-year research initiative launched in 2008 by the National Institutes of Health (NIH) with the goal of characterizing the human microbiome and its role in human health and disease. The project generated an enormous amount of data and helped to lay the foundation for future microbiome research. More recently, the American Gut Project and the International Human Microbiome Consortium have been established to further advance microbiome research and applications. These initiatives aim to create a comprehensive map of the human microbiome, including geographic variation and in response to different factors such as diet, lifestyle and medication use.

Making dietary changes to promote a healthy gut microbiota is a promising strategy. Certain foods, such as fermented foods, probiotics and prebiotics, have been shown to positively influence the gut microbiome and improve symptoms of depression and anxiety. Other lifestyle factors, such as regular exercise and stress reduction techniques, can also help support a healthy gut. In addition to the foods we eat, certain dietary patterns can also influence the gut microbiota. For example, intermittent fasting has been shown to increase the diversity of the gut microbiota and promote the growth of beneficial bacteria. In contrast, a diet high in saturated fats and processed foods can reduce diversity and promote a shift towards harmful bacteria.

With use of psychobiotics (live bacteria) to modulate neurotransmission, reduce inflammation and promote a balanced gut microbiome, there is potential to improve mood, cognition and overall mental well-being. Although research is still in its early stages, there is growing interest in their potential as a treatment for mental illnesses. One possible direction is the development of specific strains of bacteria that can be used to treat specific mental illnesses. For example, certain strains of Lactobacillus and Bifidobacterium have been shown to have positive effects on depression and anxiety in animal studies, and there is ongoing research to determine if these effects can be replicated in humans.

Another potential direction is enhancing the effectiveness of antidepressants and reducing associated side effects. There is also research underway exploring their use to delay or even prevent the onset of mental illnesses. Clinical trials on the use of probiotics during pregnancy and early childhood to promote healthy gut microbiota development can shed light on the underlying mechanisms leading to the onset of mental illnesses. As research in this area continues, there may be opportunities to develop specific strains of psychobiotics that are tailored to individual patients based on their unique gut microbiome composition and mental health status. This personalized approach could lead to more effective and targeted treatments for mental illnesses.

There are still many questions that need to be answered before psychobiotics can be widely adopted as a treatment for mental illnesses. These include determining the optimal strains and dosages of bacteria, the best delivery methods and the potential long-term effects on gut microbiota and overall health. However, the potential benefits of psychobiotics for mental health make this an exciting area of research to watch in the coming years.

Technology is playing an increasingly important role in microbiome-based therapies, particularly in enabling personalisation. Advances in DNA sequencing technology have made it possible to analyze the composition and function of the gut microbiome in great detail, and machine learning algorithms are being developed to identify specific microbial signatures associated with different health outcomes. This information can be used to develop therapies tailored to an individual's unique microbiome profile. Additionally, the use of microbiome data combined with other health data, such as genetics and clinical history, is being explored to predict an individual's risk for certain health conditions and to develop personalized nutrition recommendations. This approach is known as precision nutrition and has the potential to revolutionise the way we approach nutrition and healthcare.

Other technology-based approaches include the use of bioelectronic devices, which can modulate the activity of the gut-brain axis. For example, vagus nerve stimulation devices have been shown to improve symptoms of depression and anxiety, possibly by modulating the gut microbiome. It is possible that personalized nutrition recommendations and microbiome-based therapies could become a common treatment approaches for mental health conditions. However, much more research is needed to fully understand the complex interactions between the microbiome and mental health and to develop safe and effective microbiome-based therapies.

The Human Microbiome Project and other microbiome research initiatives will continue to play a critical role in advancing our understanding of the microbiome and its potential applications in medicine. As we uncover more about the complex interplay between the gut microbiome and mental health, there may be opportunities to develop new treatments that are less reliant on medication and more focused on promoting overall health and wellness.

Article by Goitseone Thamae. Artwork by Pauline Kerekes.