How Your Gut Bacteria May Be Talking To Your Brain

Bacteria are a big part of who we are as humans. They live all over us, forming distinct communities, or microbiomes, on our skin, in our hair, in our mouths, and in our guts. We host these microbes, and increasingly we’re learning that in turn they have a profound effect on our health. This is particularly true when it comes to the gut microbiome, which has been linked to conditions like Crohn’s disease and Irritable Bowel Disease.

The idea that the bacteria making a home in our guts have a role in our intestinal health doesn’t seem that far-fetched, but for several years there have been intriguing suggestions that our gut bacteria may also have an influence on our mental health.   

This has lead to a lot of hype around the idea that our gut bacteria may be controlling our moods or appetites to further their own ends. Experiments in mice and small-scale human studies have shown correlations between mood disorders like anxiety and depression, and alterations in gut microbiome composition.

source: www.mattniederhuber.com/PublicImages/gutbrainaxis.jpg
The gut-brain axis is like a high-speed connection between your central nervous and digestive systems.

It’s long been known that there is an intimate connection between the gut and the brain. Often termed the gut-brain-axis, this connection is like an eight lane highway facilitating a constant exchange of chemical information between the central nervous system and your belly. Ever since it was discovered in the 1980’s that bacteria produce compounds that have significant similarity to human hormones like insulin, scientists have wondered if gut bacteria may influence our mental state by producing their own sets of chemical signals.  

But the field hasn’t quite gotten far enough to definitively say how exactly that process might be taking place. This problem is particularly challenging because of how hard it is to make observations in the human gut. How can we work out what gut bacteria are doing if we can’t directly see them?  

Now, recent work from a group in Belgium has made one of the first efforts to address this question and functionally characterize how bacteria might influence mental state.  

By comparing the gut microbial compositions  and quality of life scores among a cohort of 1,054 Belgians, the group was able to test if particular bacteria were correlated with different mental health markers. While this type of association study isn’t new,  what is most exciting about their work is that they have developed a method for characterizing the neuroactive potential of certain gut bacteria.

The group built what they call “gut-brain modules,” which are essentially groups of genes associated with the synthesis of compounds with potential to interact with the human nervous system. They constructed 56 such modules, all centered around a different neuroactive molecule, such as dopamine or serotonin.  

By applying this gut-brain module framework to the gut microbial makeups of patients diagnosed with depression, they were able to identify and verify a single gut-brain module correlated with higher scores for social functioning. This module is associated with metabolism of Dopamine, a neurotransmitter that has been linked to pleasure and depressive disorders.

While this study doesn’t go so far as to argue a causative role for gut microbes in mental health, it does demonstrate a feasible approach to studying the black box of the human gut and that we may be one step closer to  understanding the role microbiomes play in our health.

Peer edited by Gabrielle Dardis.

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A Call to Guts

I’ve found that it is rather difficult to write an article when you are lying in the fetal position and afraid to move. No, I wasn’t trying to hide from a T-rex. I was having a migraine attack, and what really kept me curled up was its good friend and accomplice, nausea. According to a 2013 study, over half of migraineurs suffer from this additional punch to the stomach during the majority of their attacks. Is this collection of symptoms merely a coincidence, or are the brain and stomach in cahoots to make people miserable?

The brain “communicates” back and forth with the gastrointestinal tract via neuronal, immunological, and hormonal signals, forming what is now called the gut-brain axis. The link between the immune system and microbes within the body has already been well established, and has recently begun percolating into the mainstream media. For example, podcasts are discussing fecal transplants (yes, really) to combat gastrointestinal disease, and the hygienic hypothesis has parents thinking that maybe they should let their kids eat dirt every now and then to avoid developing allergies. Only recently has the contribution of the brain been thrown into the mix to form the microbiome-gut-brain axis.

The mutual communication between the gut (enteric nervous system) and brain (central nervous system) was discovered serendipitously, with a fascinating backstory. As scientists were attempting to form a link between the immune response, stress, and disease, they discovered that mice, when fed a bacterium that does not trigger the murine immune response but that makes humans sick, exhibited more anxious behavior. Meanwhile, animals raised in germ-free environments were less anxious. As interest in the link between behavior and biota grew, more associations between gut bacteria and emotional changes or changes in an animal’s ability to learn were discovered. This line of research has been taking off ever since.gutbrainaxis

According to PubMed, “gut-brain axis” publications per year recently nearly doubled from 75 (2014) to 146 (2016), and over 70 have already been published in 2017. Thanks to this fervor, preliminary evidence is popping up everywhere linking the microbiome, which is predominantly focused in the gut, to neurological disorders from anxiety to Alzheimer’s disease (reviewed recently in Cell). This is also jumping into the mainstream media, with such catchy headlines as, “A Yogurt a Day Could Relieve Depression.” Always remember to take such information with a grain of salt, as this information is preliminary.

So why did it take so long to find the link between this system? More often than not, scientists have been approaching the human body much like the Blind Men and the Elephant parable*: A neuroscientist grabbed a tusk and an immunologist grabbed a tail. While each scientist can make valid conclusions based on their own observations, neither can fully understand the elephant by themselves. Likewise, if scientists had continued studying the gut and the brain independently, without also considering behavior and learning, we would still be blind to their reciprocal relationship. Now, by investigating neurological health problems from a gastrointestinal point of view and vice versa, we can potentially double the chances of finding treatments for each. There is hope yet for my migraine.

*Special thanks to Dr. Keith Kelley, editor-in-chief of Brain, Behavior, and Immunity for using this in his talk at the 2016 Triangle Society for Neuroscience Spring Meeting!

Peer edited by Rachel Haake.

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The Amazing Microbiota of Brown Bears

http://www.cell.com/cell-reports/abstract/S2211-1247(16)00047-4

A brown bear’s seasonal cycle.

Image a researcher has been tasked with studying how hibernation affects a bear’s microbiota, or the collection of microorganisms residing on and in an organism. The researcher begins his day tracking brown bears until he finally finds one in a cave. His trusty veterinarian partner shoots a dart containing a potent mix of tranquilizers and narcotics at the bear. After waiting for the drugs to work, he cautiously moves towards the animal, kneels down, and collects a fecal sample straight from the bear’s rectum, sweating and praying that the bear won’t wake up to murder him.

At least that’s how I imagine the field work went for a study in Cell Reports on the gut microbiota and energy metabolism of Eurasian brown bears during hibernation. Brown bears switch between periods of heavy eating in the summer and fasting for up to half a year in the winter, during which time the bears do not eat or defecate and only urinate intermittently. Despite this extreme weight gain and obesity in the summer, bears remain metabolically healthy.

The researchers wondered how a bear’s microbiota changes throughout the seasons and how this might contribute to a bear’s healthy weight gain, and found that the bear’s gut microbiota and metabolism change with each season cycle. The researchers inserted the bears’ microbiota collected from either summer or winter into specialized mice. Soon, the mice’s own microbiota began resembling that of its summer or winter donor. Mice receiving the summer microbiota gained more fat and tended to be heavier. However, despite this increased fat mass, their glucose (sugar) tolerance was not impaired. In contrast, increased fat mass is associated with insulin resistance in humans. This suggests the bear’s microbiota plays a role in maintaining a healthy metabolism throughout its life cycle, despite extreme seasonal fluctuations in their body mass and energy metabolism. That is, the summer microbiota allow the bear to eat more without sacrificing its health. 

Studies like this one underscore the importance of studying bear biology, as it may lead to advances in how we treat disease. Imagine if we attempted to mimic a bear’s yearly cycle. We would likely suffer from kidney failure, cardiovascular disease, and muscle loss, among numerous other conditions. Yet, miraculously, brown bears avoid all these conditions, with help from their gut bacteria. This study provides a link between a bear’s healthy obesity and its gut microbiota, which suggests that the gut microbiota may be an effective target for treating obesity. So next time you see a bear, thank him…and then play dead to avoid getting killed.

Peer edited by Rachel Haake

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