It’s a Gut Feeling: What is our Gut Bacteria telling our Brain?

You have probably heard and given the sage advice to appreciate the little things in life. The message of the next few paragraphs is exactly that but I am referring to bacteria, the invisible but invincible little buggers.

We may take showers, wash our hands, clean our homes and yet they are everywhere; on us, in us, and around us. There is no escaping them. In fact, you will never be in contact with more bacteria than you carry around in your own gut. There is so much of them that they can easily outweigh your brain. In recent years, researchers have found that the bacteria in our gut communicate with the brain and vice versa. Yes, you read that right – our gut bacteria and our brain are quite chummy with each other.

[Name: Funny bacteria cartoon styles vector 01 License: Creative Commons (Attribution 3.0) Categories: Vector Cartoon https://goo.gl/4J6tmt]
Creative Commons (Attribution 3.0)
It has been known for a while that we are hosts to a multitude of bacteria and their preferred breeding ground is our gut where the majority of them reside, also known as the gut microbiome. Initially it was thought that they only help us with our digestion but in recent years researchers have found that the bacteria in our gut communicate with the brain and vice versa. A lot of research is underway to find out exactly how this communication takes place, how the food we eat is altering our gut bacteria, and the signals they send to the brain.

Changes over Time

For the longest time in human history, vaginal birth, with rare exceptions, was the only way for a mother to deliver her child11. It is largely through this process that newborns are inoculated with with the vaginal microbiota, initiating the development of the gut microbial flora (microbiome) which then takes about 3-5 years to mature.24 Initially, the infant gut microbiota remains unstable and low in diversity: breastfeeding plays a key role in forming the composition of the maturing gut microbiota.31 This process is in no way peaceful. The bacteria in our gut are highly territorial and they fight off newly ingested or otherwise invading microbes with antibiotics. In response, those invaders develop greater immunity which then leads our microbiome to develop ever stronger antibiotics. It is an ongoing arms race of epic proportions.1 Imagine all the 100+ billion humans who have ever lived14 being born and dying every single day and you would still not even come close to what is happening in your gut.

The Scale of Things

The bacteria from the mother and the environment colonize a new born baby’s gut and in just a few hours they measurably appear in their feces. In the next few days, this number ranges from 100s of millions to as many as 10s of billions per gram of fecal matter.22 And according to research published in 2016, in the first few years of a child’s life, this colony grows to a staggering 39 trillion bacteria comfortably eclipsing our own 30 trillion human cells.26 While our gut bacteria may outnumber our own cells, they make up only 1.5-4% of our body weight (1-3 kg for a 70 kg adult).

Bacteria only micrometers in size | Public domain photo by Eric Erbe, digital colorization by Christopher Pooley https://goo.gl/n79ZfD
Bacteria only micrometers in size | Public domain photo by Eric Erbe, digital colorization by Christopher Pooley

Bacterial Diversity

Your own genes are much more alike to any human being who has ever lived than the colony of gut bacteria you carry around. We are estimated to have about 20,700 human protein coding genes and 2240 types of cells.13 In contrast, according to the latest count from cross cultural samples (China, Denmark, Spain, Sweden, U.S.A.), our gut microbiome exceeds 11.6 million protein-coding genes with over 1000 species and 7000 strains17. Astonishingly, while there is a core of 71 species of gut bacteria that are found in 90% of all humans17, there is no lack of inter-human diversity with 6 million genes only shared by 1% of the population18.

Main Types of Microbiota

In a 2011 Nature article, Arumugam and colleges published the first research that identified three main types of gut microbiota (entherotypes). These are named after their respective bacterial species names: bacteroides, prevotella, and ruminococcus. They also found some dietary links, for example, individuals eating a high fat and/or high protein diet allow bacteroides to thrive while a diet high in carbohydrates enables prevotellas to flourish.2

While a lot of the research is focusing on the most common gut bacteria, the long tail is not to be discounted. Children with an overall greater genetic diversity of gut bacteria have been found to exhibit behaviors related with positive mood, curiosity, sociability and impulsivity.7 The disruption of healthy gut bacteria development can start prenatally: researchers recently found that stress during pregnancy is associated with disruption of maternal vaginal and offspring gut microbiota composition.15

Communication Pathways

The mechanisms through which the gut microbiota communicates with the brain are not currently known. Although debated, a growing number of researchers believe that the gut microbiota plays an important role in regulating bidirectional gut-brain communication via neural pathways like the vagus nerve, our immune system, and hormones.8 For example, probiotic induced gut microbiota changes have been shown to alter the behavior and neurochemicals in mice. Those same effects were not found with mice that have undergone vagotomy, a procedure where the vagus nerve is severed. This suggests the importance of the vagus nerve in making gut-brain communication possible.4

Dietary Changes

During the past few decades, the composition of human dietary patterns and with it our gut microbiota has changed drastically during the past few decades with the increased consumption of (red) meat, high fat foods, and refined sugars (more on that in one of our other blog post over here). These are the very same foods that are believed to contribute to the higher incidences of chronic inflammatory disorders, such as cardiovascular disease, obesity, depression, allergies, diabetes and autoimmune disorders.20

Banksy's caveman by Lord Jim | Creative Commons license https://goo.gl/eQyt6n
Banksy’s caveman by Lord Jim | Creative Commons license

While these large global trends seem rather bleak, there might be hope when looking at the individual level. While slightly more than 50% of gut microbiota variations are attributed to dietary changes34, what’s even more fascinating is that major dietary changes in humans can drastically alter the gut microbiota in a matter of days.9 This makes your diet the single most powerful source for you to alter your gut bacteria. If you want to get your own gut bacteria analyzed head over to the Human Food Project and order yourself a kit from humanfoodproject.com You could even do it twice to gain some insight into differences between diets.

Kit Guide

Human Food Project http://humanfoodproject.com/americangut/ | image: http://goo.gl/8dYXD6
Human Food Project | link

Animal Studies

Changes in the microbiome due to as little as four weeks on a high-fat or high-sugar diet has been shown to impair the performance of mice on various tests of mental and physical functions. This was most evident in cognitive flexibility which meant the mice had greater difficulty in finding alternative routes in mazes.19 When the microbiota of obese-type mice, induced by high-fat feeding, was transplanted into healthy controls of similar body weight, their exploratory, cognitive, and stereotypical behaviors were disrupted. Post transplant, inflammatory markers were found in the medial prefrontal cortex, suggesting that the gut microbiota is communicating via immune signaling pathways with the brain.6

Another similar study with rodents found depression23 and anxiety-like21 behavior patterns while on a diet high in fat or sugar. Similarly, mice on a magnesium deficient diet were also found to display depression-like behavior patterns.33 Other studies compare regular mice with those raised in sterile germ-free environments to eliminate the postnatal colonization of the gut. Initially, they had distinctly different stress responses but when the germ-free mice were inoculated with fecal matter from regular mice, those stress responses became more similar to one another.28 32 Each of these studies suggest that these cognitive changes are mediated by alterations of the gut microbiota through dietary patterns.

Satiety Disruption

We tend to overeat when the brain can no longer sense our bodies signals for fullness. This is exactly what happens to rats when they are fed a high-fat diet. Researchers believe this is the result of the drastic alteration of gut bacteria populations.3 One possible mechanism for this was suggested in another study where gut microbes have been shown to influence appetite via proteins they release 20 minutes after meals which suppress food intake. When researchers injected these proteins into mice and rat brains they effectively reduced appetite. How these proteins modulate appetite is not yet known but it suggests that our gut bacteria help to control when and how much we eat, potentially creating a vicious cycle.5

by RyanMcGuire | Free for commercial use https://goo.gl/6VrEib
PixaBay | (CC0 1.0)

Human Studies

A loss in microbial diversity and stability has been found when comparing the gut microbiota adapted to a hunter-gatherer societies’ diet to that of a westernized diet.25 In addition, human trials indicate that Mediterranean10, vegetarian, and vegan dietary patterns12 may beneficially impact the gut microbiota and have protective effects against metabolic and inflammatory diseases. In addition, there is substantial evidence to demonstrate that the gut microbiome is a master regulator of key neurophysiological processes that are affected in depression.27

The gut microbiota may also play a role in the development of Parkinson’s disease via the vagus nerve. A registry of almost 15,000 patients revealed that those who had their entire vagus nerve severed were half as likely to develop Parkinson’s disease 20 years later. Patients who only had it partially severed where not protected, suggesting that the gut microbiome to brain disease process heavily depends on the vagus nerve.30

Research on eating disorders has also turned to investigating links to the gut microbiota. A low diversity of gut bacteria is believed to play an important role in anorexia patients, a debilitating disease with a high mortality rate afflicting over 3 million Americans. In a preliminary study with a small sample of 16 women, researchers found that those recovering from anorexia nervosa had greater diversity in their gut microbiome.29 One big question that is currently being explored is if fecal transplants, in addition to dietary changes, could jumpstart the recovery process.16

In Conclusion

A growing number of researchers are looking at how our gut microbiome influences the brain and the varied roles that diet plays in these processes. As of now, relatively little is known and the field is still in its infancy. This is largely due to the complexities of the various gut-brain communication pathways and the role of individual nutrients. Many more clinical and in vivo studies are needed to identify how diet affects our gut microbiome and in turn our brain. And only then we can hope to identify therapeutic interventions that can restore both physical & mental health and mitigate disease causing mechanisms.

For a great presentation on gut bacteria I recommend watching this highly insightful TED Talk by Rob Knight on How our microbes make us who we are.

References

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