Monday, February 12, 2007

All in the gut

Obesity, expectedly, is influenced by various different factors. A person’s diet, exercise, genes, other health conditions and various other factors influence how fat (s)he is. There have been plenty of studies describing the influence of all these factors on fatness.

But here’s one factor you probably never thought of.

The bacteria that live within the gut.

Most of us forget the fact that we are all walking ecosystems, and our bodies (particularly our intestines) are host to millions of bacteria of many different species. Most of these bacteria are extremely beneficial, sometimes essential for us, and allow us to efficiently digest food (that otherwise would be indigestible). And most of us have experienced some dietary discomfort after a course of antibiotics (which usually don’t discriminate between the good and the bad bacteria, resulting in some upset stomachs). But we would never have thought the bacteria within us could perhaps influence how fat we are.

But that is what two really interesting studies now tell us.

It all started from some observations in mice. If bacteria were harvested from normal mice guts, and then these bacteria were infected into lab-raised germ-free mice, the germ free mouse guts would become colonized by the bacteria, and the mice would soon rapidly gain weight. This seemed to be because the bacteria were now breaking down food that would otherwise be indigestible, and so the (once germ free) mice were able to absorb many, many more calories, and therefore gain weight. This got the researchers asking if the type of bacteria in the gut could perhaps influence obesity or weight gain.

To do their studies, they had a convenient model. There are some mice, where a certain gene, called the leptin gene is mutated. These mice are very, very fat (and there is now a booming field of studies on leptin and obesity). The authors decided to compare the microbial fauna in the gut of these mice with normal “lean” mice. To do this, the authors first put in a lot of work to “shotgun” sequence the total genes of the bacteriome from the different mouse guts, and found that over 90% of the bacteria in mouse guts were from members of two (out of 70 known) bacterial divisions, Bacteroidetes and Firmicutes. What the authors saw was that in the obese mice, the relative abundance of Bacteroidetes (compared to normal mice) was 50% lower, while Firmicutes were 50% higher. This was in spite of the fact that both groups of mice were fed the same diet, and same amounts of food.

So, the next question they asked was if the two different groups of bacteria could process food differently. Their results were even more remarkable. What they saw was that Firmicutes, the bacteria that were more common in obese mice, were capable of better “energy harvesting”, and had many more proteins that could help break down indigestible food than the Bacteroidetes, to make it available for the mouse.

But was this really playing a role in weight gain?

What the authors did next was to take bacteria from obese mice or normal mice, and inject these in to normal but germ-free mice. When they did this and allowed the bacteria to recolonize the germ-free mouse guts, they saw that the mice injected with obese mouse bacteria also ended up having a higher proportion of Firmicutes than the mice injected with bacteria from normal mice. And, the mice injected with bacteria from obese mice also ended up gaining more weight than the other group of mice!

You could dismiss this as being something in mice, but does it apply to us humans as well? The authors decided to address this question as well, and found a dozen obese volunteers and five lean volunteers to do their tests on. They found that the obese people, like the obese mice, had a greater percentage of Firmicutes, and less Bacteroidetes than the thin people. Finally, the obese people went on a low-fat/ low-carb diet for a year, lost a bunch of weight, and when tested showed a steady rise in the levels of the Bacteroidetes, and a decrease in Firmicutes (the “fat” bacteria).

So, obesity can alter the microbial balance in the gut, but apparently, altering the microbial balance can also alter obesity!

Of course, anything to do with obesity is going to raise a lot of interest, and people are now going to make grand proclamations, but this study doesn’t really say if the microbes in the gut are playing a major role in obesity across the world, or if they can be used to “treat” obesity.

I personally think going for a run and cutting out the crap-food is a far better way to stay lean.

But who would have thought, the bacteria in my gut are perhaps playing games with my weight?

(Nature 444, 1027-131 (21 December 2006) and Nature 444, 1022-1023 (21 December 2006))


Wavefunction said...

Maybe a Firmicutes specific inhibitor would be a next step. Perhaps one which targets the butyrate producing enzyme...

Kiran said...

Check this one out:,65252-0.html

Most of the cells in your body are not your own, nor are they even human. They are bacterial. From the invisible strands of fungi waiting to sprout between our toes, to the kilogram of bacterial matter in our guts, we are best viewed as walking "superorganisms," highly complex conglomerations of human cells, bacteria, fungi and viruses.

Anonymous said...

Sunil, I actually ends up with a research job at A&M. Interesting health policy and social science research, although CS can be a really boring place to live in!

Sunil said...

ashutosh.....the authors did propose exactly that. But I think its a bad idea. Firstly, their studies show a complex, two-way relationship between the % of bacteria of each type and body weight, as well as body weight with % of bacteria. So, by forcibly altering one, you may have some short term benifits, but there are bound to be some more complex feedback loops. And obesity (unless it is genetic) is usually a result of bad eating habits and a lack of exercise. So, a "pill" to cure obesity isn't really going to cure'll just make people lazier. But yes....the possibility of a Firmicutes inhibitor is certainly there.'re right......we are all walking, talking ecosystems, and what's more surprising is that we know little about all the bacteria we are hosts to. An interesting aside is that the mitochondira in cells, essential for our survival, is thought to have been aquired a long, long, long time ago in the early evolution of eukaryotic cells....and may well have been a primitive, independent cell.

Ash....good for you, and CS rules!

Wavefunction said...

Sometimes I think that drug-discovery is futile, since we are fighting diseases of our own inventions!! Especially cancer and AD. Sigh.

Sunil said...

hmm.....not sure I follow you here. Are you saying cancer and AD (I assume AD is Alzheimer's disease) are human inventions?

Cancer has been around for a long, long time....and cancerous mutations in cells arise from a lot of causes, many of which are perfectly natural. And most often an aging related process...and the amyloid cascade hypothesis (currently the most accepted reason for the cause and progress of AD) doesn't have clear causes yet. It is likely that there would have been many AD patients in the past if people lived that long, but average lifespans a hundred years ago was only some 45 years...

But I completely agree that there is no "need" for drugs for some "illnesses" like obesity, which are better treated with diet and exercise.

Wavefunction said...

Well, some people see cancer and AD as inevitable disorders that arise because of our increased life span. They say that we are living an abnormal life span; for all animals, the mean lifespan is more or less prportional to their reproductive lifespan. Not so in the case of humans, where we have increased the gap between the two with better lifestyles and drugs. So they say that it is inevitable that problems like cancer and AD will afflict us; our cells are not designed for such a long lifespan. It's an interesting theory.

Sunil said...

hmm.....there may be some truth in that, and it is possible.

So, would you rather die by the time you are 50?

Wavefunction said...

hehe...good and profound question!

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