How gut bacteria ensures a healthy brain – and could play a role in treating depression

October 16, 2014 by Clio Korn
Your second brain? Credit: hey__paul, CC BY

One of medicine's greatest innovations in the 20th century was the development of antibiotics. It transformed our ability to combat disease. But medicine in the 21st century is rethinking its relationship with bacteria and concluding that, far from being uniformly bad for us, many of these organisms are actually essential for our health.

Nowhere is this more apparent than in the human gut, where the – the collection of living in the – plays a complex and critical role in the health of its host. The microbiome interacts with and influences organ systems throughout the body, including, as research is revealing, the brain. This discovery has led to a surge of interest in potential gut-based treatments for neuropsychiatric disorders and a new class of studies investigating how the gut and its microbiome affect both healthy and diseased brains.

The microbiome consists of a startlingly massive number of organisms. Nobody knows exactly how many or what type of microbes there might be in and on our bodies, but estimates suggest there may be anywhere from three to 100 times more bacteria in the gut than cells in the human body. The Human Microbiome Project, co-ordinated by the US National Institutes of Health (NIH), seeks to create a comprehensive database of the bacteria residing throughout the gastrointestinal tract and to catalogue their properties.

The lives of the bacteria in our gut are intimately entwined with our immune, endocrine and nervous systems. The relationship goes both ways: the microbiome influences the function of these systems, which in turn alter the activity and composition of the bacterial community. We are starting to unravel this complexity and gain insight into how interface with the rest of the body and, in particular, how they affect the brain.

Unravelling the gut

The microbiome-immune system link is established early on. Over the first year of life, bacteria populate the gut, which is largely sterile at birth, and the developing immune system learns which bacteria to consider normal residents of the body and which to attack as invaders. This early learning sets the stage for later immune responses to fluctuations in the microbiome's composition.

When a normally scarce strain becomes too abundant or a pathogenic species joins the community of gut bacteria, the resulting response by the immune system can have wide-reaching effects. Depression has been linked with elevated levels of such molecules in some individuals, suggesting that treatments that alter the composition of the microbiome could alleviate symptoms of this disorder.

Such an intervention could potentially be achieved using either prebiotics – substances that promote the growth of beneficial bacteria – or probiotics – live cultures of these bacteria. It is even possible that the microbiome could be manipulated by dietary changes.

In one experiment, researchers transplanted the human microbiome into germ-free mice (animals that have no gut bacteria) in order to study it in a controlled setting. They found that, simply by changing the carbohydrate and fat content of the mice's food, they could alter basic cellular functions and gene expression in the microbiome.

Anxious mice

Depression is not the only psychiatric disorder in which the microbiome may play a role. Research in rodents, as well as a few preliminary studies in humans, indicate that the state of our resident microbes is tied to our anxiety levels.

Germ-free mice, for example, appear to be less anxious than normal mice on behavioural tests of anxiety, whereas mice infected with behave more anxiously. Interestingly, there seems to be a window during development when the presence of a microbiome leads to normal levels of anxiety in adulthood: germ-free mice that were exposed to microbiome bacteria at three weeks of age subsequently behaved like normal mice, whereas those exposed at ten weeks of age continued to be less anxious than normal animals. Like the data on microbiome-immune interactions, these findings highlight the critical role gut bacteria play early in life.

This research also reveals the complexity of the relationship between the microbiome and psychological state. Although the general trend is that fewer bacteria mean lower anxiety levels, it is not just the number but the identity of the bacterial species that determine how gut dynamics interact with mental state.

For example, adding through probiotic treatment may reduce elevated caused by inflammation and infection. A key factor in this relationship is stress and the way the body responds to it.

Another brain

Researchers have shown that the presence or absence of microbes in young mice affects the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis – a key pathway in the body's stress response system. The activity of the microbiome during development thus sways how we respond to future stressors and how much anxiety they cause us.

How do the bacteria in our gut wield such influence over our brains and bodies? The mechanisms of microbiome-host interactions appear to be as numerous and varied as the interactions themselves.

Gut microbes help break down food into its component parts, so the molecular building blocks available in the body depend in part on which bacteria are present to extract them. This can influence brain function by, for example, affecting the availability of molecules needed to make neurotransmitters.

Some gut bacteria can even alter neurotransmitter levels directly by converting glutamate – an excitatory transmitter – into GABA – an inhibitory brain chemical. And , along with neighbouring intestinal cells, communicate with a branch of the called the enteric nervous system (ENS) whose neurons surround the entire gastrointestinal tract. This part of the nervous system is so sophisticated that many refer to it as the body's second brain.

The study of microbiome-gut-brain interactions is still young, yet it is already spurring the development of new branches of medical research. At this rate, it is poised to become one of the most fascinating stories in neuroscience.

Explore further: Gut microbiome analysis improved noninvasive colorectal cancer screening

Related Stories

Gut microbiome analysis improved noninvasive colorectal cancer screening

August 7, 2014
Analysis of the gut microbiome more successfully distinguished healthy individuals from those with precancerous adenomatous polyps and those with invasive colorectal cancer compared with assessment of clinical risk factors ...

Type 1 diabetes: Gut microbiota networks may influence autoimmune processes

March 12, 2014
The interactions of the gut microbiota in children with typical diabetes autoantibodies differ from that in healthy children. The fact that these differences already exist before antibodies are detectable in the blood adds ...

Diet affects mix of intestinal bacteria and the risk of inflammatory bone disease

October 2, 2014
Diet-induced changes in the gut's bacterial ecosystem can alter susceptibility to an autoinflammatory bone disease by modifying the immune response, St. Jude Children's Research Hospital scientists reported. The findings ...

Is the gut microbiome a potential cause and therapeutic target for autoimmune diseases like multiple sclerosis?

August 7, 2014
Numerous risk factors are believed to contribute to the development of autoimmune disorders such as multiple sclerosis, and new research is focusing on the role that bacteria in the gastrointestinal tract as well as other ...

Navel gazing: Healthy gut bacteria can help you stress less

January 13, 2014
Striking new evidence indicates that the gut microbiome, the ecological community of microorganisms that share our body, has a huge effect on brain function – much larger than we thought.

Diverse gut bacteria associated with favorable ratio of estrogen metabolites

September 11, 2014
Postmenopausal women with diverse gut bacteria exhibit a more favorable ratio of estrogen metabolites, which is associated with reduced risk for breast cancer, compared to women with less microbial variation, according to ...

Recommended for you

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Feyn Man
5 / 5 (2) Oct 18, 2014
This should be a massive news story! This needs FAR more attention. Great article!!
SURFIN85
5 / 5 (1) Oct 20, 2014
I'm looking forward to the day when newborn babies aren't pumped full of antibiotics... when metric buttloads of human antibiotics aren't fed in bulk to meat animals... when they aren't sprayed over crops everywhere... when the people who profit from harming human health and advancement in the name of a cheap burger are castrated and beaten in the streets...

I got an infected cut on my big toe a couple weeks back. It swelled up and gave me a little fever. I laughed and stayed home from the hospital, saved my deductible, and kicked its butt within a few days- I'd like to thank my genes, which for hundreds of thousands of years have been handed down to me by tough characters who wouldn't blink at what sends most modern people scurrying for a security blanket. I'd like to also thank my immune system, which did its typical excellent work, SWAT team style. And of course my gut microbiome, I couldn't do without you guys.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.