The bacterial zoo in your bowel

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.

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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., Doré, 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

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