Mental Illness Beyond the Mind: The Brain-Microbiome Connection
Welcome to the first post of a new Said and Dunn blog series called “Beyond the Mind” by Kristin Nishimi and Janine Cerutti. In this series, we will explore the relationship between the mind and the body – how the two talk to each other and why this communicative relationship matters for mental illness. Although mental illnesses are brain diseases (and the brain is embedded in the body), this series examines how the rest of the body may influence brain disease and vice versa. The ultimate goal of this series is to better understand how much of this this brain-body connection is a two-way street.
Throughout history, there has always been discussions about the links between the body and the mind — the idea that the mind impacts the body and vice versa is not new. But when it comes to researching brain health, much of modern psychiatric research has focused solely on the brain. And although this neuro-focused research has the potential to broaden what we know and how we think about brain disease, if we focus only on the brain, we may be missing the bigger picture. Research into brain-body connections may provide important clues about what puts people at higher risk for mental illness…how our bodies react to stress and subsequently affect symptoms…and novel psychiatric treatments targeting physiological processes outside the brain.
In this series, we will examine the ways that current research is extending beyond the brain to other aspects of physical and physiological health. We will explore the connections between various physiological systems (some more unlikely than others!) with respect to the development, progression, and consequences of brain disease, with a focus on mental illness. Our hope is that readers will develop a broader, potentially more comprehensive picture of mental illness and brain health.
To kick off the series, we chose a “hot topic” that has been gaining attention across a variety of disciplines. From nutrition, biology, public health, neuroscience, to psychiatry— the human microbiome seems to be hitting headlines everywhere. But how does it impact mental health?
1. What is the Human Microbiome?
The human microbiome is composed of all the microbes (bacteria, fungi, protozoa, and viruses) that live on and inside our body. One human’s microbiome is estimated to have over 100 trillion microbes – outnumbering our human cells ten to one – and the majority are living in our gut (a.k.a mostly in our intestine), making the gut microbiota of particular interest to researchers, scientists, and nutritionists alike. A healthy adult microbiome is typically home to more than 1,000 species of bacteria and its microbes combined have 200 times the number of genes as humans, which is around 23,000. The sheer magnitude of the microbiome is why some people consider it to be an honorary organ. It may even weigh as much as five pounds – that’s roughly the weight of a brain!
2. Why is the microbiome important?
The microbiome is essential for human development and growth, immune defense, as well as nutrition and digestion. It helps us to digest food, regulate our immune system, protect against harmful pathogens, and produce vitamins like Vitamin K. Many factors can affect the structure or state of the microbiome that can in turn impact a wide array of physiological processes which it’s involved in. For example, long-term dietary habits, such as high protein or high fiber diets, influence our gut microbiota composition, while infections and antibiotics can temporarily alter its stability. When the microbiome’s normal state is disrupted, things can start to go awry…
Dysregulations or changes in the normal state of the microbiome have been associated with a number of diseases and infections, such as irritable bowel syndrome, inflammatory bowel disease, cardiovascular disease, clostridium difficle (c.diff) infection, autoimmune diseases like diabetes, metabolic diseases like obesity, and even psychiatric diseases — which we’ll unpack in a minute.
With all this considered, the microbiome has rightfully received increasing attention over the last decade as worldwide research initiatives, like the Human Microbiome Project (HMP) launched in 2008, are attempting to map the human microbiome (discovering new microbe species along the way). The goal of this project and others is to better understand the microbiome’s role in our physical and mental health, and to better investigate ways in which we can manipulate it to treat disease and improve our overall well-being.
3. How does it relate to mental health?
Increasingly, evidence from neuroscience suggests that the gut microbiome and the brain are as thick as thieves…(or very strongly connected, if you don’t speak in idioms). Studies have reported that many neuropsychiatric disorders — like autism, depression, anxiety, and schizophrenia — are associated with variations in the gut microbiome. There is also evidence from human and animal studies to suggest that our gut microbiota play an important role in the development of our hypothalamic-pituitary-adrenal (HPA) axis — think stress response or reactivity and even continue to act on it over the life course. For example in one study, researchers found that mice who were separated from their mothers (a pretty stressful experience for humans and mice alike!) had changes in their gut microbiota. The HPA axis is just one promising pathway in which the microbiome may be linked to anxiety, stress, and trauma-related disorders and also depression.
Speaking of depression, depression is a mood disorder that is associated with dysregulation of the HPA axis. Although we do not know yet if imbalances in the microbiome cause depression (or other mental illnesses), one study recently found that after transferring fecal microbiota from persons with diagnosed depression to microbiota-depleted rats, the rats started to display depressive-like symptoms (e.g., anhedonia and anxiety). This was the first experimental study to demonstrate that the gut microbiome may be playing a causal role in the development of depression. But will get more into causality in the next section.
The communication between the gut and the brain has come to be known as the microbiota brain-gut-axis, and it is part of an elaborate physiological network including the central nervous system, the endocrine system, the immune system, the autonomic nervous system, and the enteric nervous system. Though scientists are only recently able to map the gut microbiome and to examine its relationship with mental health, the concept of this microbiota-gut-brain axis, or the idea that our gut and brain are constantly communicating, dates back over 100 years. From a psychiatrist infamously believing microbes on teeth was a source of mental illness, reports of successful treatment of melancholia by Lactic acid bacillus, and the proposed beneficial effects of fermented milk on a range of health outcomes, ideas regarding the gut-brain connection date back to the early 1900s. With modern technology and statistical techniques, we have come a long way in uncovering the interactions between the gut microbiome and brain health.
4. What is the state of current research?
Now that several studies have identified gut-mental health connections, researchers are investigating dimensions of the gut microbiome that may be harmful or beneficial. Much of the current work aims to identify potential protective microbiome constituents, harmful bacterial metabolites, or epigenetic signatures associated with the development of mental illness. For example, a recent article found that Faecalibacterium and Coprococcus bacteria were associated with higher quality of life, while Dialister was depleted in individuals with depression. While this research is promising for treatment and prevention of brain disease, there are few rigorous, prospective studies to date and often findings are inconsistent across study populations.
Moving beyond simple associations, research is beginning to delineate the mechanisms of the connection between the gut microbiome and mental states. Multiple possible pathways through which the gut microbiome could impact behavior and mental health have been identified, such as the autonomic nervous system, the HPA axis we mentioned earlier, and circulating inflammation. Physiological pathways have been largely studied with animals, though work is being done to replicate findings in humans.
Other current efforts are working to disentangle directionality — do gut microbiome dysbiosis impair mental health, does mental health disrupt the gut microbiome, or is there a bidirectional relationship? Most studies assess dimensions of the gut microbiome as predictors of mental health, with some evidence that microbiome-based therapy can impact psychological status. Fewer studies have investigated the impact of mental health on the gut microbiome. However, there is evidence of other biological dysregulation resulting from mental illness, e.g., HPA axis dysregulation, immune dysregulation, and associations between mental illness and other gut-related issues like inflammatory bowel disease. Taken together, it is possible that chronic mental illness might lead to alterations in the gut microbiome, but without longitudinal or experimental data, it has been difficult to get a clear picture of the direction of these effects.
5. Implications and what’s next?
Therapeutic implications of the gut-brain-axis are beginning to be explored with studies testing prebiotics, probiotics, and dietary approaches to treat mental illness. There may be promise for using what we are learning about the gut microbiome for diagnostics and predictors of treatment response in psychiatric illness, though research is still in its very early stages.
Work on the gut microbiome and mental illness is inherently holistic and integrated - spanning multiple body systems across the microbiome-gut-brain axis, and thus will require interdisciplinary efforts — where experts from multiple specialties come together (gastroenterology, microbiology, epidemiology, informatics, psychiatry and psychology, just to name a few) to identify risk and resilience for adult and pediatric disease. Future research should aim to include more ethnically and socio-culturally diverse samples, longitudinal studies to uncover disease progression and changes over time, and large sample sizes potentially via collaborations and consortia. This research will continue to push the field beyond a one-sided view of mental health that is largely focused on the brain, and ultimately identifying a more holistic picture of mental health in the body.
