You are outnumbered by a factor of 10 to one, by forces you cannot see. Your body has around ten trillion cells, but it's also home to a hundred trillion bacteria. For every gene in your genome, there are 100 bacterial ones. Most of these are found the dark, dank environment of your bowel but their incredible diversity is being brought to the surface. Say hello to the gut metagenome.
Together with a team of international scientists, Junjie Qin and Ruiqiang Li from BGI-Shenzen had the unenviable task of studying the bacteria from the faeces of 124 Europeans. They used a formidable and audacious technique called metagenomics, which analyses all the genetic material in a sample, without bothering to culture the individual species first. It's a shoot-first-ask-questions-later method that captures all the data and lets other programmes sort out the mess.
Stool samples from 33 people have already been analysed in this way, but Qin and Li managed to sequence almost 200 times as much DNA. Brace yourself for some big numbers. Their project uncovered just under 3.3 million bacterial genes, more than 150 times as many as reside in the entire human genome. By their estimate, your bowel and mine harbour at least 160 bacterial species each and we share many of our tenants (I say bacteria, but around 1% of the genes came from archaea, a superficially similar group but one that's actually as different from bacteria as bacteria are from us).
The quest to understand gut microbes may seem like an arcane niche of science, but it's actually very important for public health. We rely on these microscopic passengers more than we realise. They harvest energy from our food, provide us with nutrients that would otherwise be denied to us, prevent the growth of harmful bacteria, and more. In many ways, they're like a forgotten organ. They can also go rogue, changing their community in ways that are linked to obesity or bowel diseases. Indeed, Qin and Li showed that the gut microbiome of a health person looks very different to that of someone with a bowel condition like Crohn's disease or ulcerative colitis.
All in all, over 1,000 species make their living in the human bowel but a common cadre of 57 are shared by the vast majority of us. Even for this common set, each individual species could be thousands of times more common in your gut compared to mine. With such variation, it's no wonder that earlier smaller studies concluded that people have very different gut lodgers.
Of the 3.3 million genes, most are fairly rare. Some 2.3 million of them are found in less than a fifth of the people in the study. There is, however, a set that is shared across all bowels. Some of these core genes as "housekeepers", essential for the survival of any bacterium, but others are specific requirements for life in the bowel.
The latter group include genes for sticky proteins that allow the bacteria to latch onto the cells of their hosts, essential when your home is constantly washed by tsunamis of digested food. Others are all about sugars - they harvest, break down and ferment these complex molecules from their nutritious surroundings, including several sugars from fruits and vegetables that we don't absorb very well. Yet others produce vitamins and fatty acids that we'd otherwise lack and some may even help to convert unusual chemicals, like the food supplement benzoate (E211), into useful substances like the vitamin biotin. The majority, however, are still a mystery, and that's just the essential genes. There are millions more with functions still to be unpicked.
So far, the data reads like a litany of massive numbers and impressive stats. But the true value of Qin and LI's work is as a source of data for future discoveries yet to come. Jonathan Eisen from University of California, Davis says, "Much of the science in here is not that novel but the scope of this project alone is awesome. This is most valuable as a reference data set for future work." He adds that we still need to decipher the genomes of many other gut microbes, to give us reference sequences that can be compared against the sprawling mass of data thrown up by Qin and Li's study. For the moment, the best way to do that is to take the species that can already be identifed, and sequence close relatives that can be cultured in the lab. In the not-too-distant future, it should also be possible to seqeunce the genome of a single cell.
Once this work is done, we can start to answer some of the more intriguing questions. How, for example, does the gut metagenome interact with our own squadron of genes? How does it change when people put on or lose weight, when we get gut infections or when we develop bowel cancer? How are these passengers influenced by our diet or other aspects of our environment? And so far, the team have only examined European faeces. Who knows what revelations lurk within the poo of other nations?
Reference: Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan, M., Batto, J., Hansen, T., Le Paslier, D., Linneberg, A., Nielsen, H., Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li, S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J., Brunak, S., DorÃ©, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J., Weissenbach, J., Antolin, M., Artiguenave, F., Blottiere, H., Borruel, N., Bruls, T., Casellas, F., Chervaux, C., Cultrone, A., Delorme, C., Denariaz, G., Dervyn, R., Forte, M., Friss, C., van de Guchte, M., Guedon, E., Haimet, F., Jamet, A., Juste, C., Kaci, G., Kleerebezem, M., Knol, J., Kristensen, M., Layec, S., Le Roux, K., Leclerc, M., Maguin, E., Melo Minardi, R., Oozeer, R., Rescigno, M., Sanchez, N., Tims, S., Torrejon, T., Varela, E., de Vos, W., Winogradsky, Y., Zoetendal, E., Bork, P., Ehrlich, S., & Wang, J. (2010). A human gut microbial gene catalogue established by metagenomic sequencing Nature, 464 (7285), 59-65 DOI: 10.1038/nature08821
More on gut bacteria:
- Gut bacteria - fat or thin, family or friends, shared or unique
- Human gut bacteria linked to obesity
And I thought I had a shit post-doc...
What a great article! well done - I'm sending this to all my friends who wonder why I love microbiology...
How about the difference between meat eaters and vegetarians?
If people are interested in the dataset they can also download it via BioTorrents:
Microbiology is so not my area, but I couldn't help but notice a quasi-link between this post, your later one on the research connecting specific mouse-gut bacteria with obesity, and this guest post over at Aetiology: http://scienceblogs.com/aetiology/2010/02/c-sections_allergies_and_prob… about vaginal versus C-section birth processes and correlated outcomes of gut microflora colonization in newborns. So, I wonder... if the mouse research holds true for humans too and if a mother has this "bad" bacteria (listed in the other post) that is linked to obesity, and gives birth vaginally, then does that put the infant at increased risk for obesity straight from birth?
Ooh interesting call. Inheritance of gut bacteria is not the only route that mice could inherit a higher risk of obesity from their parents - check this out.
Interesting, I think I remember this one now; and I did not mean to imply that might be the "only" route, was just musing about the synergy of these concepts. Funny, but this describes my significant other: "..the ever-present gene also blocks signals in the animals' brains that tell them that they're full." <>
"The latter group include genes for sticky proteins that allow the bacteria to latch onto the cells of their hosts"
Absolutely intriguing! My wife has celiac disease which manifests when one of the proteins that make up gluten, gliadin a long chain of amino acids, is not completely broken down by digestive enzymes, and for unknown reasons, when this longer chain attaches to an enzyme in the small intestine called tissue-transglutaminase, the body interprets this union as toxic and the immune system attacks it. Maybe this will bring a new avenue to research of the disease?
How would you go about discovering if one or several bacteria were related to digestion of the protein gliadin? Determine if is similar in different people, and different or unique in celiac patients?
And the laymanâs question, can you introduce bacteria of this nature to an individual?
How would you go about discovering if one or several bacteria were related to digestion of the protein gliadin?>/blockquote>
Never heard of that protein, but it should be as easy as: Make an agar plate with gliadin, put bacteria on it, see if the gliadin is broken down.
And the laymanâs question, can you introduce bacteria of this nature to an individual?
In a word, yes. But it's a bit more complicated than that. Adding bacteria (like the yoghurts advertising "good bacteria") is a big enough area of research becuase there's money in it. For functinoal foods, enough of the bacterial culture has to survive the food processing and the passage through your digestive system. You can avoid that problem if you're willing to go up instead of down, but that isn't as in demand, understandably.
The problem there's no real getting around is making the bacteria establish themselves in sufficient numbers.
There's trillions of bacteria in your gut, and they're all competeing with each other. The bacteria has to be able to survive, and in suffcient numbers to have the desired effect. If the bacteria can survive in your gut, I would speculate that it's very likely already present. If it can't, there's no hope for adding it as it is, so a similar bacteria (or at least one which can do what you want) which can survive must be found, and if necessary/possible optimised for survival (genetic manipulation through genetic engineering or through selective breeding).
Take everything I've said with a pinch of salt though, because I'm only basing this on my undergrad and the odd talk from scientists in this area.
Thanks for Post 9 Marc
I really appreciate the input. This potential avenue to understand celiac disease may have been pursued already? But in the sampling of the research papers I have read on this subject matter I have not come across this link in the research.
I will inquire with a celiac research center at the University of Columbia to see if they are aware of approaching it from this direction.
Another interesting line of research would be the effect on this gutsy ecosystem of antibiotics, both (a) over the time they are being prescribed, and (b) over the long haul.