Wednesday, January 28, 2009

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.

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