Tuesday, November 20, 2012

Microbiome Part 9: The Finale--Bacteria and Mood

Note: This program first aired on November 17, 2012.

This week, we wrap up our exploration of bacteria and the microbiome with a final look at the world within us; the cutting edge of human microbiome research. What scientists are discovering is the fact that the bacteria in your gut can influence your mental state. So not only do they digest your food, synthesize your vitamins, regulate your immune system and keep their pathogenic brethren in line, they also strongly influence how calm, anxious, bold or depressed you might happen to be.

Several recent studies on mice have demonstrated this effect quite clearly. In one study, the behavior of “normal” mice was compared to mice who were fed a diet that included a probiotic supplement. The probiotic mice proved to be less anxious and more confident in behavioral tests, and had lower levels of the stress hormone cortisol in the their urine.  In another study, two different strains of mice were compared, one bred to be passive and timid and the other bold and courageous. When bacteria from one mouse strain were transplanted into the other mouse strain, the “transplantee’s” behavior changed to match the behavior of the donor mouse strain. In other words, putting bacteria from a passive mouse into a bold mouse can make a bold mouse passive. Putting bacteria from a confident mouse into a timid mouse can make a timid mouse confident. This shows that the personality traits we have come to think of as having a genetic basis (the scientists who bred those strains of mice certainly thought that), are in fact quite plastic and seem to depend on composition of the gut microbiome rather than genetic code.

In a rather circular piece of logic, it also seems that the mind can influence the population and diversity of the gut flora as well. In times of stress, gut flora becomes less diverse and robust, creating openings for more serious dysbiosis and disease—think of it as an extreme case of butterflies in the stomach. So the bacteria influence the mind, and the mind influences the bacteria, and around and around the maypole they go.

So how does this work? The literature refers to the rather heady “brain gut enteric microbiota axis”, but the actual mechanisms of communication are not completely well known as of yet. A few things are quite clear. The gut houses a huge amount of nervous system tissue, so much so that it is commonly referred to as our “second brain”. This second brain is connected to our first brain by the vagus nerve, a large bidirectional nerve pathway that originates in our brain stem and invenerates almost all of our viserca*. Most of the neurons in the vagus nerve are sensory, they collect information about the state  of the viserca and send it back to the brain. The remaining neurons carry info from the brain back to the viserca. In the first mouse experiment I discussed, the one with the probiotic-ed mice, when researchers severed the vagus nerve in those probiotic supplemented mice, the treatment effect vanished. So the probiotics may still have been in the gut, but the anxiety reducing effect of them could no longer be communicated to the brain. This tells us that at least in that experiement, the vagus nerve played a huge role in communicating whatever the probiotic bacteria were doing.

It has also been noted that the nervous system tissue in the gut produces many significant neurochemicals, including all the big ones like serotonin, dopamine, GABA, norepinephrine, and acetylcholine. It turns out, the gut bacteria make these chemicals too, many of which down regulate the excitability factor in the brain leading to enhanced calm. What isn’t clear is if it is really the bacteria that are responsible for the neurochemicals that we always ascribed to the nervous system tissue in the gut. And the actual means of communication between the gut and brain has not been fully parsed out. The vagus nerve is clearly part of it, but these neurochemicals must play a role as well.  And all of this has huge implications for medicine and treatment of everything from mental illness to autoimmune diseases.

The day is coming when your personal ecosystem will be easily assessed, imbalances identified and addressed, and health restored, all on the basis of your individual mix of microbial flora. I personally am incredibly excited about this, and look forward to the day when we in western medicine, work with our microbiomes, instead of exclusively against them, acknowledging our place in the much bigger we are just a part of. The tide is turning.

*Everything except our spleen, for some reason…


Gut bacteria and mood—the mouse study

Gut bacteria in infancy determine happiness (via serotonin levels)

Gut bacteria and anxiety and depression

A great overview from the American Psychological Association and Dr. Siri Carpenter, Sept. 2012 http://www.apa.org/monitor/2012/09/gut-feeling.aspx

The show that started all this wondering for me, RadioLab. Take a listen here: http://www.radiolab.org/2012/apr/02/gut-feelings/

Emmanuel Denou, Wendy Jackson, Jun Lu, Patricia Blennerhassett, Kathy McCoy, Elena F. Verdu, Stephen M. Collins, Premysl Bercik. The Intestinal Microbiota Determines Mouse Behavior and Brain BDNF Levels. Gastroenterology, Vol. 140, Issue 5, Supplement 1, Page S-57

Microbiome Part 8: Human Symbionts

Note: This program first aired on November 7, 2012.

Most of us can accept and understand, perhaps subconsciously, that our guts are full of bacteria, and that those bacteria help digest our food.  We’ve talked about this in recent weeks and it is a concept most of us are comfortable with: If there are bacteria on our bodies, your gut, that wild independent ecosystem within you, is exactly where you would expect them to be.

The problem is, our gut isn’t the only place bacteria live on our bodies, and digesting food isn’t the only thing they do for us. Human beings have literally been described as mammal/bacterial symbionts,  organisms completely and utterly at the mercy of the symbiotic relationship they have evolved with microscopic partners over millions of years, organisms that are actually collections of trillions of organisms—one big one and billions of little ones. One source even calls it “the human super organism”. Now to be fair, I am sure this symbiosis is not limited humans, though I am not familiar with studies of the microbiome of the domestic house cat, or the elephant, or of dolphins ( as a side note: It is very likely that this research has been done, or at least proposed). I think that when we look closely, we realize that our definition of life as we know it has to change. We find that without exception what we used to call an individual organism is in fact an accumulation of organisms working in concert. Its true: no man is an island. And nature isn’t red in tooth and claw, its symbiotic.

So when you look at the human organism, you find bacteria not only in the gut, but everywhere else on the body as well. And just like in the gut, these bacteria in all the other places in our body are doing a job for us. An excellent example is on our skin. We are covered head to toe with bacteria, and amazingly it is not a homogeneous community. I remember being amazed by some of the first research that came out on the human microbiome; it outlined the discovery that the bacteria on your right hand are a completely different community than the bacteria on your left hand. Each area of the body is a distinct ecological niche for our bacterial partners.

The bacteria on our skin play a similar role to the bacteria in our gut, in that they help prime the immune system, keeping it at the ready without stimulating full blown activation. More interestingly they seem to regulate their own community with the checks and balances we see in any ecological system. For example Staphylococcus epidermis is a very common skin bacteria (hence the epidermis name), and while generally innocuous, can result in some nasty infections, especially in the immunosuppressed or otherwise ill. There is evidence though, that it also secretes antibiotic compounds (endogenous antimicrobial peptides to be exact); these compounds are the bacteria’s own chemical warfare against competing bacteria. Many other sampled skin bacteria do the same. Their infighting is our benefit, by releasing all these anti biotic compounds on our skin, they keep each other in check, never allowing one type to grow to the point of becoming pathogenic. That is why you should go easy on the hand sanitizer and antibacterial soap. These products can disrupt the balance of bacteria on the skin, and lead to more pathogenic bacteria in the long run.

So our coconspirators in this thing we call the human superorganism not only keep our immune system tuned and ready for action, they also police themselves, to our benefit. When their balance gets disrupted, by antibiotics, ultra clean living or some other environmental insult, or when you get dealt a weak hand (coming out the sun roof instead of the “normal way” is a fast and sure way to start out life with a microbiome deficit) your microbiome is less able to manage itself, leading to dysbiosis and a whole host of illnesses. So don’t micromanage your microbiome. Let them do their work and attend to their own bacterial business.  In most instances, you’ll be better off for it.


Check out the good work by the folks at the Human Food Project: http://humanfoodproject.com/

The title of Michael Specter’s article in the Oct 22, 2012 New Yorker says it all: “Germs are Us”—if you haven’t read it, run out and get it. It will make you want the Heliobacter pylori bacteria in your stomach!

Lynn Margulis was really on to something when she wrote Symbiotic Planet (1998 Basic Books ISBN 0465072712)

“The skin’s secret surveillance system” Nature July 26, 2120 http://www.nature.com/news/the-skin-s-secret-surveillance-system-1.11075

Great article from Germany’s Spiegel “Western Lifestyle Disturbing Key Bacterial Balance” 9/21/2012 http://www.spiegel.de/international/zeitgeist/western-lifestyle-leading-to-dangerous-bacterial-imbalances-a-856825.html

On the skin biome—“Skin microbiota: a source of disease or defense?” From the British Journal of Dermatology, March 2008 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746716/

Wednesday, November 7, 2012

Microbiome Part 7: Human Bacterial Partnerships

Note: This program first aired on October 27, 2012.

It should be clear to you, if you’ve been following this show for the past several weeks, that bacteria influence every aspect of life on Earth. Omnipresent, that is how you should think of bacteria. From the endosymbiosis theory of the origins of chloroplasts for photosynthesis, and mitochondria for energy metabolism to the nitrogen fixing role of symbiotic microbes in plant roots, bacteria are intimately involved in all biological processes. They even single handedly support the non photosynthetic ecosystems of the deep ocean hydrothermal vent communities, supporting life without light, something we used to think of as impossible.

I want to turn our gaze inward now, to the cutting edge of medicine and microbiology, to the human microbiome. Our bodies are a vast universe and play host to thousands of different kinds of life forms. There are estimated to be more bacterial cells on and in our bodies than there are human cells, by at least an order of magnitude. It turns out, we’re actually more than the sum of our parts.  We function more like a forest ecosystem or a coral reef than the individuals we once thought we were.

All of these microbes evolved right along with us, over the millions of years of hominid evolution. Our microbiome has been even been described as an additional organ, one we all have that most of us have no awareness of whatsoever. These bacteria we host fill many ecological roles in our bodies, and in return get a stable and generous living environment. They do so much for us in fact, that without them we could scarcely live. Remember when I talked about bacteria as external digesters? Most of them (and certainly all the ones we are talking about now) are heterotrophic and must ingest nutrients from outside their bodies. The two to five pounds of them living in our guts at any given time are doing just that; digesting all that food we swallow. We physically break the food down into smaller pieces, and we even synthesize some enzymes that chemically break down the food molecules into smaller more absorbable bits. What we can’t or don’t digest (primarily certain complex carbohydrates and fibers) we give to our gut flora, that two to five pounds of bacteria we carry around in our intestines. As decomposers, they are able to at least partially break down the less digestible components of the food we eat, and we can benefit from this. That digested food can be absorbed by our cells. Some of the byproducts of this bacterial digestion are the short chain fatty acids that are so critical to many metabolic pathways, and are thought to play a an anti inflammatory role in the body as well. The microbes also synthesize certain essential vitamins and cofactors that are not otherwise found in the food we eat.

From a nutritional standpoint, our gut flora close a loop that we are not capable of closing on our own, we’ve never had to evolve complete chemical digestion because we’ve been co-evolving with our symbiotic microflora for millions of years. In the coming weeks we will look beyond the simple digestive symbiosis, and explore the various other ways the human microbiome affects and improves our quality of life. 


The New York Times did several articles on the human microbiome this summer, in conjunction with the release of the NIH Human Microbiome project report.

Kolata, Gina “In Good Health? Thank your 100 Trillion Bacteria” New York Times, June 13, 2012

Zimmer, Carl “Tending the Body’s Microbial Garden” New York Times, June 18, 2012

Also, from 2010: Zimmer, Carl (he’s a leading American science writer, who’s latest book is on microbes) “How Microbes Defend and Define Us” New York Times, July 12, 2010

Direct from the source: The National Institute of Health’s Human Microbiome webstite: http://commonfund.nih.gov/hmp/index.aspx, http://www.hmpdacc.org/

“The structure, function and diversity of healthy human microbiome”—one of the seminal articles from the Human Microbiome Project

Small intestinal bacterial overgrowth happens when large bowel bacteria get into the small bowel (think Girls gone wild meets Mardi Gras), and raise havoc. We tend to think of the gut flora as being in the colon, but there are bacteria in the small bowel too, just less of them and of a different type http://www.medicinenet.com/small_intestinal_bacterial_overgrowth/article.htm