Our Brains, Our Guts, And What We Consider to Be Ourselves

What’s happening in your “gut” may be affecting what’s going on in your brain.

As a new area of research, this might sound a little far-fetched, but it’s really happening. We have known for years that we have “helpful” bacteria living within us, and they are important to our digestive health. What we are now starting to find out is that these bacteria may also play important roles in our mental health, and anyone who suffers from a mental illness will tell you, our mental health has far reaching effects for our overall well-being.

A few months ago, President Obama announced an initiative to fund research into the microbiome. For me, this is exciting for a few reasons, namely due to the fact that one of the best ways to make the jump from Early-Career Scientist to Mid-Career Scientist is to secure your own funding. Besides that, the microbiome represents a relatively unknown area of science that may shine some light on some very complicated questions. You know, the usual exciting science stuff.

The traditional definition of Microbiome is the study of the collective genomes of microbes (fungi, bacteria, viruses) that live within a distinct habitat. Based on this definition, we can survey a small, ecologically-distinct area (the soil 6 inches deep in an old-growth forest, the human small intestine, the lichen on a downed log, etc), then extract and sequence the genetic material to discover the diversity of microorganisms living within these distinct spaces.

Several studies have done this, and the general consensus is that there are incredibly high numbers of bacteria within these ecologically-distinct systems. Now, the focus is not so much the genetic diversity (still important), but has headed toward a second, more ecologically-focused definition: the collective activity of the fungi, bacteria, and viruses that live within an ecologically-distinct habitat. In other words, vast, diverse communities of microbes don’t just sit there. They eat, excrete (don’t think about it), communicate, reproduce (lots), and in many instances, transfer genes between themselves. The big questions remain: how are these different species co-existing? What does this mean for the higher life forms (plants and animals) they colonize?

An effort to organize and classify the work done on microbiomes of the human body has yielded the National Institute of Health’s Human Microbiome Project,¹ a database that organizes all of the genetic work done on five ecologically distinct areas of the human body: skin, airway, gut, urogenital, oral, as well as a sixth, miscellaneous classification. Collections are sampled from the healthy, as well as no-so-healthy individuals, so that we may characterize the differences between microbiomes of healthy and ill individuals.

For me, the most striking result from human studies thus far has been the sheer number of bacterial cells found, estimated to be about 10¹⁴-10¹⁵ just within the intestinal tract. This is 10-100 times higher than the number of eukaryotic cells found within the body.² On a case-by-case basis, the bacteria that colonize us may be symbiotic (awesome!), commensal (thumbs up), pathogenic (thumbs down), or a combination of these categories, depending on the population density and the presence of other species.

What exactly are these bacterial cells doing? What do they want? Do they have goals? Are they helping us? Hurting us? Do they help each other? Are they trying to destroy each other? Are we really just a walking, breathing, eating framework to supplement all the different microbes within us?

This is where it gets really complicated.

Traditionally, there have been three major functions of our microbiome: First, they collectively protect us from pathogenic bacteria through competition of resources (you can’t sit with us), secondly, they fortify the intestinal epithelial barrier to limit bacterial movement into tissues (none shall pass), and thirdly, they help us break down indigestible dietary molecules (nom) to improve our uptake of vitamins and other nutrients.

Now, we potentially have a fourth role: to protect us from harmful collective stress responses, which may result in everything from generalized anxiety disorders and depression, to diseases caused by low-level inflammation, such as irritable bowel syndrome and Crohn’s disease. In fact, some studies are hypothesizing that this list of neuro-psychiatric disorders could potentially be expanded to include autism and Alzheimer’s disease (reviewed in ^{3 4}).

It’s been established that signaling pathways connect the nervous system, the endocrine system, and the immune system, and we know that the gastrointestinal system can also trigger the central nervous system (gut-brain axis).⁴ The recent findings suggest that this occurs through signaling by gut bacteria. One of the many theories is that if our gastrointestinal microbiome is shifted to less-than-optimal conditions, a systemic stress signal is activated.

Behind every emotional state, including stress, there is a synthesis and release of hormones. In the case of stress, these hormones are namely adrenaline and cortisol, which trigger signaling cascades resulting in the fight-or-flight response (elevated heart rate, movement of glucose into the bloodstream, altered immune system response), while shutting down “unnecessary” bodily functions including digestion. The stress response has been great for us on an evolutionary basis, but we can imagine that the cumulative effects of chronic stress make us rather ill. Problems such as anxiety, depression, digestive problems, headaches, sleep problems, weight gain, and memory/concentration issues have all been linked to chronic stress.⁵

Now we have a bit of a chicken and egg scenario: what came first? Are chronically-elevated levels of stress preventing us from maintaining an optimal microbiotic balance? Or is it our poor microbiotic balance keeping us vulnerable to the effects of chronic stress?

Timing is very important when it comes to establishing a microbiome. The human fetal gut lacks any kind of significant biotic colonization; the microbiome is established very shortly after birth, and the completed signature is present within less than one year.⁶ This colonization is thought to happen primarily through close contact with humans, particularly mom. This implies that there is a short window of opportunity for us to establish an optimal microbiome, and it’s the establishment of this microbiome that is necessary for us to maintain good neuropsychiatric health throughout all of our lives.

Of course, this brings into play the importance of sufficient maternity leave, but that’s a topic for another time, and probably another author.

At this point, there are still tons of known unknowns, hence the drive to fund research into this area.

Here are some questions that we still have:

What are some of the microbiome community dynamics? Is the presence of some species “better” for us than others? What exactly is an “optimal” condition?

What are the origins of the microbiome? When and why did bacteria start colonizing higher life forms?

How does the host genetic makeup affect the microbiome?

What are the effects of antibiotics on the microbiome?

How can a microbiome be altered to improve overall health?

Should I let my toddler eat dirt? Their own boogers? Should I be eating dirt or my own boogers?

Obviously, there is still quite of work to be done. But in the meantime, eat healthy, get sufficient rest, make sure you walk about 10,000 steps each day, and just imagine yourself as some sort of planetary entity, a Mother Earth-type vehicle for masses of thriving bacterial specimens that are eating, reproducing, dancing and singing to that great cosmic order.

¹ Human Microbiome Project

⁶ Sekirov, I., et al. 2010. Gut microbiota in health and disease. Physiol Rev. 90:859-904