Every Man an Island, Pt. 1

ResearchBlogging.org

No man is an island, entire of itself

— John Donne, Meditation XVII

Scanning electron microscope images of <i>B. thetaiotaomicron</i>, a prominent human gut bacterium, and the intestine.  From: Human Gut Hosts a Dynamically Evolving Microbial Ecosystem Gross L PLoS Biology Vol. 5, No. 7, e199 doi:10.1371/journal.pbio.0050199
Scanning electron microscope images of B. thetaiotaomicron, a prominent human gut bacterium, and the intestine. From: Human Gut Hosts a Dynamically Evolving Microbial Ecosystem Gross L PLoS Biology Vol. 5, No. 7, e199 doi:10.1371/journal.pbio.0050199

Only one out of ten cells in our body is human

In a certain sense, every man is an island; this interesting finding comes from Jeffrey Gordon’s lab in Washington University. To understand why that is so, we need to understand something about the make up of our bodies. Adult human bodies are comprised of 1013 cells. These cells are broadly divided into different types that compose the tissues and organs that make us function the way we do. However, those are not all the cells that are in the human body. In addition to our own cells, we have 1014 bacterial cells that reside in and on us. Think about it: only one out of ten cells in our bodies contain the DNA inherited from our parents. The other nine cells are not human.

Most of the bacterial cells in our body  are located in our gut, about 1.5 kg of bacteria. All along our gastrointestinal tract really, from our mouth to our anus. The others are on our skin, our respiratory system (lungs, trachea, nose) and ears. These bacteria too, are roughly divided into different types that perform different functions, some of them actually beneficial to us. Skin bacteria, mostly benign, actually prevent the colonization of our skin by disease causing bacteria. Our  mouth is a slightly different story: the bacteria sitting on our teeth form plaque, a rough surface which accelerated the colonization by by other bacteria that metabolise sugar into acid. This acid eats through the tooth enamel and causes dental caries. That is why we wage a constant battle with toothbrush and toothpaste against bacteria. Other interesting stories are associated with our respiratory tract, our ears, and the upper GI tract.

But today we will talk about our gut, the bacteria that live there and some surprising findings on how they affect, and are affected by, our body weight.  Oh yes, and why every man is an island.

“It’s not your fault, it’s your gut microflora”

Two years ago, Gordon’s group published two papers that made quite a splash both in the scientific world and in the popular media.  They have shown that there is a difference in the bacterial taxonomic composition between obese and non-obese humans. They have shown that obese mice and people harbour in their guts a dominant population from the bacterial division Firmicutes. At the same time, lean  people (or even those on a weight-loss diet) and lean mice,  have less bacteria from the Firmicutes division and more from the Bacteroidetes division.  To try and understand why that is, they performed a comparative metagenomic functional analysis of mouse gut bacteria. They compared a sample of  DNA sequences extracted from the population of bacteria in the guts on lean mice,  to DNA sequences from bacteria in obese mice. They found that in obese mice the gut bacterial population contained more enzymes that broke up complex carbohydrates, like starch.  Other experiments showed that indeed, the population of bacteria in obese  mice break up  complex sugars more efficiently; that is, the bacterial populations of obese mice provide their hosts with smaller sugar molecules that are readily absorbed through the gut, creating a vicious feed-forward cycle:  if you are a fat mouse, you will get more calories from the same piece of chow than if you are a lean mouse. Their conclusion was that the human gut bacterial population is intimately connected with what we eat. High poly-carbohydrate  foods eventually enrich their consumers’ guts with carbohydrate loving bacteria; and those, in turn, “reward” their hosts with the back-handed compliment of making more simple and easily absorbable carbohydrates available to them, making them fatter.

So here is another another way in which bacteria affect our well-being: our gut flora controls our caloric intake.  Consider a slice of whole wheat bread, about 100 calories.* This means that the actual caloric intake from a slice of bread will differ between individuals. Unfortunately, it is the fatter person who will, quite probably, receive more calories from eating the same slice of bread, because his gut bacteria will deliver more available calories to him.

This is not the first time such an observation was made. In 2004 the Gordon lab published a paper in PNAS, where they showed that Bateroidetes theta suppresses the formation of FIAF: Fasting-induced Adipocyte Factor. FIAF normally prevents the creation of fat, but high level of B. theta, associated with stress in humans, induce both a higher intake of carbohydrates, and the formation of fat from that intake.  Here is a case of bacteria exerting a hormonal influence on our bodies affecting our energy balance and our weight.

So we have an incredibly intimate association with the bacteria in our bodies, at times as strong as that we have with our own.. actually, it’s getting hard to distinguish where we end and where our microflora begins. Well, not really: a eukaryotic cell with the DNA we got from mom and dad in a double package of 23 chromosomes is probably more ours than a prokaryotic cell with a single or double chromosome. The point is that the bacterial population is as important to our well being as some of our “human-cell” tissues.

But do all obese people have the same microflora? How much of  our own genetic makeup influences our bacterial gut population and thus our body weight? And  what about the headline “Every Man an Island”, what does that have to do with anything?   Well, I’m pretty much getting to the end of this post, so please be patient, part 2 is coming up with some more interesting insights; and an explanation of the headline.


* Yeah, I know. The scientific measure is really 100 kilocalories. I am using the grocery-store parlance that most people use, even scientists; especially scientists on a diet.


Peter J. Turnbaugh, Ruth E. Ley, Michael A. Mahowald, Vincent Magrini, Elaine R. Mardis, Jeffrey I. Gordon (2006). An obesity-associated gut microbiome with increased capacity for energy harvest Nature, 444 (7122), 1027-131 DOI: 10.1038/nature05414

Further reading:

To be Continued…

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13 Responses to “Every Man an Island, Pt. 1”

  1. Shirley says:

    This is such fascinating stuff. And just when we were starting to dream about going from genotype to phenotype, we learn it’s not just our genotype we have to consider. Who knew the environment wasn’t just whether we smoked or whether we exercised, but these trillions of other organisms?

    Looking forward to the next post!

  2. idoerg says:

    Shirley :
    This is such fascinating stuff. And just when we were starting to dream about going from genotype to phenotype, we learn it’s not just our genotype we have to consider. Who knew the environment wasn’t just whether we smoked or whether we exercised, but these trillions of other organisms?
    Looking forward to the next post!

    Yes. We have to consider the genotype of our microbiome as well: the “other human genome”. The NIH is funding the sequencing of the species that are considered to be “core species” so we will have a set of reference genomes for gut metagenomic studies. The only hitch is that there does not seem to be a core of species in the gut microbiome. There is more and more evidence that our gut microbiomes have no core intersection of common phylotypes, but rather a core of functionalities. See the second part of this posting.

  3. Paul Crowley says:

    The scientific measure is of course kilojoules.

    So when a thin person eats a slice of bread, where does the energy that they don’t make use of go?

  4. Keith - Hermosa says:

    The logical interpretation is that the human body cannot keep up with
    the digestion of absurd amounts of food (2 to 10 times as much as a
    human is supposed to eat), thereby leaving undigested food in the
    stomach. That undigested food becomes an available food source for
    bacteria who take advantage of its presence. This is not the same
    thing as “fat people are being fed more by bacteria,” implying, of course, that it’s not their fault.

    These “scientists” should go into finance. Wall Street is looking for some sharp minds like these. It’s this sort of deep thinking that has blown up the world’s economy.

  5. Chan says:

    I’m sorry but I’d have to agree with Keith. This sounds so much like scientific holistic/new age interpretation. I have always maintained that effective digestion is a product of two main mechanisms, physically by chewing and chemically by enzymes and overwhelming by HCL (stomach acid). Nutrition is absorbed in the upper digestive tract where the population of bacteria is low or non-existence. For people with large population of gut bacteria, they either consume too much food or the two mechanisms broke down, leaving undigested food for bacteria to consume.

    The bacteria are there to benefit themselves mostly.

    As for strains of bacteria in certain type of people, the observed evidence doesn’t always imply a cause.

    On an unrelated note, I have a cure for the common cold. Check it out – http://www.youtube.com/watch?v=0UVHeULP1JA

  6. Emac2 says:

    Keith – Logical interpretation?

    I think you miss the point if you think this has anything to do with who is to blame.

    A lot of thin people eat too much as well and this helps explain why these people do not lose weight while some fat people can’t even lose weight when they diet – especially if they diet by eating low fat high carb foods.

  7. Jimmy says:

    So, basically, if I ingest something that will kill off these Firmicutes bacteria, then I’ll slow down the availability of the simple sugars that are making me fat? Huh, so, what fits the bill to kill bacteria – clorox seems like a bad choice, I’ll go with hydrogen peroxide. Thanks!

  8. tetsu96 says:

    @Jimmy
    That’s exactly what I thought at first. Clorox and Hydrogen Peroxide are probably a bad idea, but I wonder if an Antibiotic detox followed by reintroducing certain bacteria (acidophilus as example) would be an effective way to “reboot” a person’s gut. Or would it do more harm then good? Maybe I’ll spend time with sick people until I catch something to justify this experiment.

  9. idoerg says:

    tetsu96 :
    @Jimmy
    That’s exactly what I thought at first. Clorox and Hydrogen Peroxide are probably a bad idea, but I wonder if an Antibiotic detox followed by reintroducing certain bacteria (acidophilus as example) would be an effective way to “reboot” a person’s gut. Or would it do more harm then good? Maybe I’ll spend time with sick people until I catch something to justify this experiment.

    One thing Gordon’s group did in the first paper was exactly that. Only with mice. They took germ free mice and inoculated them with bacterial populations taken from lean and obese mice. The germ free inoculated with obese mice bacteria gained more weight than those inoculated with lean mice. Although statistically significant, the weight gain difference was not that large.

  10. p says:

    I have a maybe stupid question. We know an adult is about 60Kg, but he/she has only 10^13 cells according to your post. The 10^14 bacterial cells are approximately 1.5 Kg. It doesn’t make sense to me. Though most of our body is water, how could the ‘dry body’ be much less than 1.5 Kg if we assume the cells have nearly the same weight?

  11. Iddo says:

    @p

    p :
    I have a maybe stupid question. We know an adult is about 60Kg, but he/she has only 10^13 cells according to your post. The 10^14 bacterial cells are approximately 1.5 Kg. It doesn’t make sense to me. Though most of our body is water, how could the ‘dry body’ be much less than 1.5 Kg if we assume the cells have nearly the same weight?

    Therein lies the rub: bacterial cells and human cells do not have the same weight. Human cells outweigh bacterial cells by x1000. A bacterial cell weight about 10^-12 grammes, a human cell is 10^-9 grammes or so. If the typical human outweighs his / her bacterial cells by 100, the numbers come about just right.

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