The Microbiome-Gut-Brain Axis: Are Gut Microbes the Key to Treating Mental Health Disorders?

brainWe’re slowly learning more and more about the trillions of bugs that inhabit the human body, and it’s becoming increasingly clear that our “second” genome doesn’t only impact our physical health, but also has a significant impact on our mental state. I’ve previously written about the microbiome in relation to mental disorders such as ADHD and autism, and also how the gut microbiota affects our appetite and food preferences. In this post I’ll highlight some new research, summarize what we know about the gut-brain axis at the moment, and explore what the future holds in this exiting field of research.

Microbiome-gut-brain axis

Signals travel bidirectional between the brain and the gut through the vagus nerve.

Signals travel bidirectional between the brain and the gut through the vagus nerve.

The enteric nervous system in our gut is often called the second brain, and this mesh-like system of neurons can communicate with the brain in our head through the vagus nerve. While it was assumed for a long time that communication travelled primarily from the brain to the gut, we have now learned that the gut also signals the brain, and that this gut-brain axis is involved in a multitude of physiological processes including satiety, food intake, and regulation of glucose and fat metabolism (1).

Recent studies have made it clear that microorganisms (gut microbiome) play an essential role in this communication process, and researchers are now finding that the microbiome-gut-brain axis doesn’t only have an impact on our appetite and metabolism, but also influences our behaviour, thoughts, and mood (2,3).

We’re still learning about the complex interaction between bacteria and the mind, but it seems that bacteria also can communicate with the brain by manipulating the immune system and producing their own versions of neurotransmitters (4).

The current belief is that gut dysbiosis changes the communication between gut and brain through several different mechanisms, and that alteration of this link may contribute to psychiatric disorders (5,6,7,8,9,10).

What does the research say?

General behaviour and brain activity

  • Animal studies show that gut microbiota influence brain chemistry and behavior independently of other factors, and that germ-free mice display increased motor activity and reduced anxiety compared to mice with normal gut microbiota (11,12).
  • A human study found that “four-week intake of a fermented milk product with probiotic by healthy women affected activity of brain regions that control central processing of emotion and sensation” (13).

Depression and anxiety

  • Studies in mice show that probiotics can reduce stress-induced corticosterone and anxiety- and depression-related behavior (14).
  • Humans with major depressive disorders are under systemic oxidative stress and low-level chronic inflammation (15,16,17).
  • Inflammation and oxidative stress can be both a cause and a consequence of depression (18).
  • Increased intestinal permeability, small intestinal bacterial overgrowth, and translocation of bacterial endotoxins seem to play an important role in anxiety and depression (19,20)
  • “Stress, depressive symptoms and high levels of anxiety are characteristically associated with increased frequency of fast-food choices and over-consumption of high-energy, low nutrient density foods” (21). All factors that establish an inflammatory microbiota.
  • Food with a beneficial effect on the gut microbiota often improves symptoms of depression (22).
  • Manipulating the gut microbiota is a potential treatment for major depression and anxiety (23,24).

Autism spectrum disorders

  • Both studies in animals and humans show that patients with autism have an altered gut microbiota, and there seems to be a strong correlation of gastrointestinal symptoms with autism severity (25,26,27,28)
  • Patients with autism spectrum disorders have alterations of the intestinal barrier (29,30).
  • “…dietary or enteric bacterially produced short-chain fatty acids may be plausible environmental agents that can trigger ASDs or ASD-related behaviors” (31).
  • Recent research shows that probiotic therapy alleviates autism-like behaviors in mice (32).
  • Probiotics and other ways of manipulating the gut microbiome could soon be used in the treatment for autism and other neurodevelopmental disorders (33,34).

Schizophrenia

  • Gastrointestinal inflammation is a relevant pathology in schizophrenia (35).
  • Increased intestinal permeability and endotoxemia promote inflammation in patients with schizophrenia (36).

Obsessive-compulsive disorder

  • A new hypothesis proposes that the root cause of OCD is dysfunction of the gut microbiome, which results in susceptibility to obsessional thinking. This hypothesis is partially based on the fact that OCD is often triggered by antibiotic use, stressful life events, or other factors that potentially disrupt the community of microbes living in the gut (37).

Other disorders

The microbiome-gut-brain axis is an expanding area of research, and it’s still unclear which role microbes play in the etiology and pathogenesis of most mental health problems. We are just beginning to scrape the surface of the complex interaction between the microbiome and the brain, and although controlled trials are lacking, it’s likely that gut bugs play a role in ADHD, bipolar disorder, alzheimers, and other types of mental illness.

It’s not all in your head

The terms “mental disorder” and “psychiatric illness” can actually be quite misleading since we now know that mental disorders are associated with increased intestinal permeability, alteration of the gut microbiota, inflammation, oxidative stress, and other metabolic and physiological problems. It’s time to stop looking at the brain as a separate organ, and rather aknowledge that mental disease is closely linked to what happens elsewhere in the body.

Increase in mental illness correlates with changes in the human microbiome

There has been an increased prevalence of mental health disorders during the last couple of decades, and some epidemiologists are now talking about psychiatric illness as a global epidemic (38). It’s interesting to note that during the same time period, the human microbiome has undergone drastic changes. Antibiotics, western diets, c-section, bottle-feeding, and decreased consumption of “live”, probiotic foods are just some of the factors associated with the urban, western lifestyle, that promote dysbiosis in the gastrointestinal tract.

While this correlation in itself doesn’t prove anything, it’s not unlikely that microbes, who constitute 90% of our cells and 99% of our DNA, have an impact on our mental state..

Treatment

Some probiotics produce neuroactive substances that act on the gut-brain axis. E.g., serotonin

Some probiotics produce neuroactive substances, such as serotonin, that act on the gut-brain axis.

While more human studies are needed before we can say anything concrete about the benefits of manipulating the microbiome in the treatment of mental illness, some researchers have already begun testing certain organisms – psychobiotics – that are used specifically to deliver neuroactive substances that act on the gut-brain axis (39,40,41)

Although investigating the use of specific organisms in the treatment of mental disorders could be useful, the key to treating gut dysbiosis is to alter the gut microbiota in a way so that the “good” bacteria are able to flourish and pathogens are suppressed. The only hard evidence we have to go on from scientific studies is that probiotics such as lactobacillus and bifidobacterium improve symptoms of depression, and autism.

However, considering the available data, it’s highly likely that manipulating the gut microbiome can be useful in the majority of mental health disorders. Just taking a probiotic supplement will have little to no effect, rather it seems that a combination of diet, fermentable substrates, soil based organisms, fermented food, etc. is necessary to see any significant improvement.

Severe gut dysbiosis is usually harder to treat, and microbiota transplantation is often the only way to overcome the pathogenic overgrowth. It’s also possible that antimicrobials could be used in the treatment of gut dysbiosis.

Some health practitioners such as Dr. Natasha Campbell-McBride have already begun treating mental health disorders by manipulating the microbiome. She has worked with hundreds of children with autism, ADHD, etc. and says that addressing gut dysbiosis is the key to treating mental illness.

Hopefully, clinical trials in humans will soon be published, and advanced probiotics containing entire bacterial communities will be available to people suffering from gut dysbiosis.

A word of caution

While I’m personally convinced that the microbiome has a significant impact on our brain and behaviour, there is still a lot to learn about the interaction between microbes and the brain, and how we can manipulate the microbiome to our advantage. It’s also important to understand that although we know that microbes impact our mental health, we don’t know the extent of the involvement.

Chronic stress and depression in itself can change the bacterial composition in the gut, and therefore it’s often hard to determine cause and effect. However, the fact that changes to the microbiome often precedes the onset of mental health problems like OCD, and probiotics and other measures of changing the gut microbiome have successfully been used in the treatment of many health problems, suggests that it really is an axis where the brain affects the gut microbiota, and the microbiota affect the brain.

Although some health practitioners have successfully treated patients with mental disorders by manipulating their gut microbiome, there are no comprehensive human studies investigating the use of microbiota transplantation, prebiotics or probiotics in the treatment of mental disorders such as autism, ADHD, and OCD, and treatment is therefore largely experimental.

How gut microbes are able to influence our brain

Recommended reading for everyone interested in the microbiome-gut-brain axis

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  1. […] microbiota had alterations in the brain region called the hypothalamus, and since we know that gut bacteria impact our mood, behaviour, and thoughts, this shouldn’t really come as a […]

  2. […] thoughts: I’ve previously talked about the microbiome-gut-brain axis, and given what we know about the connection between microbes and mental health it doesn’t […]

  3. […] By now it’s well established that gut microbes impact mood and brain function through the microbiome-gut-brain axis. Given the evidence that is coming out, it’s definitely time to start including the gut […]

  4. […] It’s well established that gut microbes affect the brain through the microbiome-gut-brain axis. […]

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