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Not Exactly Rocket Science
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The many yous in you – what Lydia Fairchild has in common with a sponge and an anemone »

Divided by language, united by gut bacteria – people have three common gut types

Europe is a divided land. For such a relatively small continent, it is split into 50 different countries and its people speak hundreds of languages. But within their guts, there is common ground. The intestines of Europeans, like those of all humans, harbour massive communities of bacteria. According to a new study, these microscopic worlds fall into just three different groups, which transcend the borders of geography and politics. In gut bacteria, we are united.

Our gut contains trillions of bacteria, known collectively as the microbiome. Their cells outnumber our own by ten to one. We are, to the closest approximation, thriving communities of bacteria encased in a human shell. No two people have quite the same collection – we differ slightly in the species we contain, and there can be hundreds jostling for space.

But this variation isn’t infinite. Previous studies have shown that once people reach adulthood, their microbiomes become remarkably stable. Even after the communities are rocked by antibiotic assaults, they rebound to their old selves, recruiting members in the same proportions as before. Now, Manimozhiyan Arumugam and Jeroen Raes from the European Molecular Biology Laboratory (EMBL) have found that these constraints go even further. There seem to be just three preferred ways of building a community of gut bacteria.

The duo collected stool samples from 22 Europeans from Denmark, France, Spain and Italy, sequenced all the DNA within them, and compared them to 13 similar samples from Japan. They found that these sequences collapsed into three general groups, which they called enterotypes. Arumugam and Raes also showed that sequences from 154 Americans and 85 Danes, taken from other studies, fit within the three groups.

The enterotypes transcend boundaries of countries and continents. That is surprising – two years ago, John Novembre showed that the genetic variation in Europe mirrors its geography with startling precision. But human genes are outnumbered by those of their gut bacteria by a hundred to one, and these bacterial genes are apparently far more straight-forward.

Enterotypes aren’t quite as well-defined as, say, blood groups, but they could have similar uses as medical markers. The microbiome helps us to digest our food and it affects our susceptibility to diseases; the enterotypes could reflect these roles. Each enterotype was dominated by a specific genus of bacteria, and varied in the proportions of the other members. They produce energy in subtly different ways, they’re particularly efficient at breaking down different nutrients, and they specialise at creating different vitamins.

These are clues, but they stop short of telling us what the three enterotypes signify. Peer Bork, who led the study, says that the groups don’t seem to be driven by diet. However, his team has only looked at Westernised or developed countries. It’s possible that more enterotypes lurk in the guts of hunter-gatherers from remote villages; after all, one earlier study found that African villagers have different gut bacteria to Europeans.

The enterotypes aren’t driven by the age, gender, nationality, or body weight of their hosts either. However, they could be affected by their hosts in more subtle ways. For example, the gut bacteria of older people contain more genes that are involved in breaking down carbohydrates than those of youngsters, but they have fewer genes that help them cope with harsh conditions. These changes could reflect the bacteria’s responses to their ageing human hosts, whose failing digestive systems need more help and whose weakening immune systems pose less of a problem.

It’s clear that this line of research is just beginning. “This is the first hint that there might be types of gut microbiome that are reproducible in different populations,” says Rob Knight, who also works on gut bacteria. “It will be fascinating to determine in future work whether these enterotypes are associated with disease risk and reproducible in other populations and ages.”

“I do think the enterotypes will have an impact on human health,” says Bork. His team has found hints that everyone with a certain disease belong to just one enterotypes, although for now, he isn’t revealing which disease it is. That will come in time…

Reference: Arumugam, Raes et al. 2011. Enterotypes of the human gut microbiome. Nature http://dx.doi.org/10.1038/nature09944

<p>You could be sitting alone and still be completely outnumbered for your body is home to trillions upon trillions of tiny passengers – bacteria. Your body is made up of around ten trillion cells, but you harbour <em>a hundred </em>trillion bacteria. For every gene in your genome, there are 100 bacterial ones. This is your ‘microbiome’ and it has a huge impact on your health, your ability to digest food and more. We, in turn, affect them. Everything from the food we eat to the way we’re born influences the species of bacteria that take up residence in our bodies.</p>
<p>This slideshow is a tour through this “<a href="http://www.nytimes.com/2010/07/20/opinion/20tue4.html?_r=1">universe of us</a>”. Every slide has links to previous pieces that I’ve written on the subject if you want to delve deeper. Or download a podcast of <a href="blogs.discovermagazine.com/notrocketscience/2011/10/19/i-microbes-my-radio-4-talk-on-the-hordes-of-microbes-inside-us/">my Radio 4 programme on these hidden partners</a>.</p>
<p>Image by David Gregory &amp; Debbie Marshall, Wellcome Images</p><p>To our microbiome, the human body must seem like an entire planet, full of different ecosystems. This is especially true for those that <a title="Permanent Link to The bacterial zoo living on your skin" href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/06/23/2009/05/28/the-bacterial-zoo-living-on-your-skin/">live on our skin</a>. At the microscopic scale, the hairy, moist surface of your armpits is as different from the smooth, dry skin of your forearms as a rainforest is to a desert.</p>
<p>In a thorough survey of our skin microbiome, Elizabeth Grice identified species from at least 205 different genera. Your forearm has the richest community with an average of 44 species, while your nostril, ears and inguinal crease (between leg and groin) are the most stable habitats. Grice also found at bacteria from a specific body part have more in common than those from a specific person. Your butt microbes have more in common with mine than they do with your elbow microbes.</p><p>Despite its diversity, the skin microbiome is a tiny country village compared to the <a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/06/23/2010/03/03/the-bacterial-zoo-in-your-bowel/">bustling metropolis inside your bowels</a>. The dark corridors of your intestine house more bacteria than any other part of your body. A team of international scientists led by Junjie Qin and Ruiqiang Li discovered that each of our bowels carries at least 160 bacterial species. Together, our collective guts have just under 3.3 million bacterial genes, more than 150 times as many as reside in our own genomes. They also showed that the gut microbiome of a healthy person looks very different to that of someone with a bowel condition like Crohn’s disease or ulcerative colitis.</p>
<p>Despite this diversity, Peer Bork has shown that the gut bacteria of people from Europe, North American and Japan collapse <a href="http://blogs.discovermagazine.com/notrocketscience/2011/04/20/divided-by-language-united-by-gut-bacteria-%e2%80%93-people-have-three-common-gut-types/">into three enterotypes, or gut types</a>. These clusters cut across age, gender, body weight and nationality. Each produces energy in a slightly different way, manufactures a different vitamin and may affect our susceptibility to different diseases.</p>
<p>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.</p>
<p> </p>
<p>Image by Med. Mic. Sciences Cardiff Uni, Wellcome Images</p><p><a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/06/23/baby%e2%80%99s-first-bacteria-depend-on-route-of-delivery/">We inherit our microbiomes from our mother</a>, picking up billions of them as we slide from her largely bacteria-free womb through her microbe-laden vagina. Being slathered in vaginal microbes might not seem like much of a treat but it’s vital for a newborn.</p>
<p>Babies end up with a very different portfolio of skin and gut bacteria depending on how they are delivered. Those who are born naturally harbour a more diverse array of bacteria, which resemble those in their mother’s vagina, including several species that are important for digestion. Those who are delivered by C-section are colonised by a less diverse array of bacteria, including some like <em>Staphylococcus</em> that are picked up from the hospital environment.</p>
<p>These early differences could directly affect a baby’s health for these first colonisers determine which the species that will follow. The bacterial heirlooms that babies inherit from their mothers might act as a shield, preventing more dangerous microbes like from setting up shop. By changing baby’s first bacteria, C-sections could alter the make-up of their later communities, leading to long-term effects on health and nutrition.</p><p><a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/08/03/you-are-what-you-eat-%e2%80%93-how-your-diet-defines-you-in-trillions-of-ways/">Our microbiome is like a hidden organ</a>, helping us to break down foodstuffs that our own cells cannot cope with. And in turn, our food affects our microbiome. Our first set is laden with genes for digesting milk proteins, allowing us to make full use of our only source of nourishment as babies. Breast milk might even have evolved to nourish the most beneficial bacteria with special sugars.</p>
<p>Just before we move onto solid foods, our microbiome starts activating genes that break down the complex sugars and starches in plants, preparing us for the menu to come. As our diet diversifies, so do our bacteria. They activate genes that use carbohydrates effectively, produce vitamins, and break down unusual and diverse chemicals. As adults, our microbiome becomes relatively stable, but its membership roster depends on the food we eat. The guts of African villagers who eat high-fibre diets are dominated by plant-digesting specialists, which are much rarer in the guts of Europeans who eat high-fat diets.</p><p>Before the age of better food hygiene, our meals used to provide a rich source of foreign bacteria that our microbiome could plunder for genetic tools. Bacteria trade genes as easily as humans trade gifts. For example, the gut bacteria of Japanese people have borrowed genes from a marine species, which now <a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/04/07/gut-bacteria-in-japanese-people-borrowed-sushi-digesting-genes-from-ocean-bacteria/">allows them to digest the special carbohydrates in seaweed</a>. The marine bacterium eats seaweed, including the types that are used to make nori, a common sushi ingredient.  In the past, when diners wolfed down morsels of nori, some also swallowed seaweed-eating bacteria, which traded genes with those in their own guts.</p>
<p>This wouldn’t happen nowadays because nori is roasted before being eaten. In fact, processing food presents a blockade to bacteria from the outside world and as a result, Western gut communities have become gentrified. They lack genetic diversity, and they have few ways of increasing it.</p>
<p>Images by Alice Wiegand, Alex Kovach, Tristan Barbeyron and Mirjam Czjzek</p><p>The microbiome is more than just our partners-in-digestion – they affect our health too. They have been linked to a variety of medical conditions, including allergies, immune diseases, and even obesity. For example, the balance of the two major groups – the Bacteroidetes and Firmicutes – <a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/06/23/2008/10/06/human-gut-bacteria-linked-to-obesity/">could influence our body weight</a>.</p>
<p>Fat mice and humans have a less diverse milieu of gut bacteria, with a <a href="http://blogs.discovermagazine.com/notrocketscience//notrocketscience/2008/12/01/gut-bacteria-fat-or-thin-family-or-friends-shared-or-unique/">greater proportion of Firmicutes to Bacteroidetes in their bowels</a>. This ratio increases if we eat high-fat diets and falls if we eat low-fat diets. And if the gut bacteria from fat mice are transplanted into mice with no gut bacteria of their own, they can make the new hosts overeat and pile on the pounds. This research suggests that gut bacteria could be manipulating us for their own ends. Some species send out signals that make us hungrier, encourage us to eat more, and affect the way we store fat. And some of our immune genes help to moderate these signals.</p>
<p>As we learn more about our bacterial partners, we might eventually find ways of influencing them to improve our health. This is already happening. In 2008, Alexander Khoruts from the University of Minnesota managed to cure a woman with a “vicious gut infection” by giving her <a href="http://www.nytimes.com/2010/07/13/science/13micro.html?_r=2&amp;pagewanted=1">a transplant of her husband’s gut bacteria</a>.</p><p>What happens in the gut doesn’t stay in the gut – it sometimes affects the brain. Animal studies have started to show that the microbiome, from its staging ground in the bowel, can influence the development of its host’s brain.</p>
<p>Rochellys Diaz Heijtz found that <a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2011/01/31/gut-bacteria-steer-the-development-of-the-young-brain/">germ-free mice, without any microbiome</a>, were more active, less anxious and less risk-averse than usual. Their brains differed in the activity of over a hundred genes that provide cells with energy, influence chemical communications in the brain and strengthen the connection between nerve cells. Heijtz could even shift her germ-free mice towards “normal” behaviour and genetic activity by giving them a microbiome transplant, but this only worked early in their lives.</p>
<p>But later,  Javier Bravo  at University College Cork managed to<a href="http://blogs.discovermagazine.com/notrocketscience/2011/08/29/from-guts-to-brains-%e2%80%93-eating-probiotic-bacteria-changes-behaviour-in-mice/"> change the behaviour of normal adult mice</a> by feeding them with a probiotic bacterium  called <span id="apture_prvw1" class="aptureLink"><span class="aptureLinkIcon" style="background-position: right -1348px;"> </span><span class="aptureLink snap_noshots"><em>Lactobacillus rhamnosus</em></span></span>,  often found in yoghurts and dairy products. The bacterial menu changed  the levels of signalling chemicals in the rodents’ brains, and reduced  behaviours associated with stress, anxiety and depression.</p>
<p>Meanwhile, Gil Sharon found that <a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/11/01/gut-bacteria-change-the-sexual-preferences-of-fruit-flies/">gut bacteria can shape the sexual choices of flies</a>. Flies that are raised on diets of starch prefer to mate with other “starch flies” while those raised on maltose prefer “maltose flies”. When Sharon dosed the flies with antibiotics, she killed both their gut bacteria <em>and </em>their sexual preferences. If she inoculated the sterile flies with the microbiome of their peers, their preferences reappeared instantly. It’s possible that the bacteria influence the levels of sex pheromones that affect the fly’s attractiveness.</p>
<p>These studies show that you can’t understand an animal’s evolution simply by considering the evolutionary pressures that act on its genome. You also have to consider the genes of the bacteria and other passengers that live inside it. We’re each like a superorganism – a unified alliance between the genes of several different species, only one of which is human.</p>The teeming masses of the microbiome also contain a record of our evolutionary past. Howard Ochman found that the <a href="http://blogs.discovermagazine.com/notrocketscience/notrocketscience/2010/11/16/gut-bacteria-recap-the-evolution-of-apes/">evolution of the gut microbes in great apes</a> perfectly recaps that of their host. The bacteria from the two species of gorilla are more closely related to each other than they are to human gut bacteria. Geography, diet and disease aside, the main thing that influences the members of these bacterial cities is the species of the host. You could reconstruct the evolution of the apes, simply by comparing the bacteria in their bowels.<p>The bacteria of our microbiome are mostly our allies. <a href="http://blogs.discovermagazine.com/notrocketscience/2011/10/13/beneficial-gut-bacteria-can-become-virus-collaborators/">But they can also they can be turned against us.</a> Two new studies in mice have found  that viruses - including one that causes polio, and another that causes cancer - can exploit gut bacteria to infect our bodies.</p>
<p>They use molecules on the bacteria's surfaces as reins, to ride towards host cells, or backstage passes to sneak past the immune system. Our microscopic allies can turn into  unwitting collaborators for dangerous infections.</p>
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April 20th, 2011 by Ed Yong in Bacteria, Microbiome | 11 comments | RSS feed | Trackback >

11 Responses to “Divided by language, united by gut bacteria – people have three common gut types”

  1. 1.   Robert S-R Says:
    April 20th, 2011 at 1:30 pm

    Wow. This seems huge. I wonder what medicines might work differently for people with different “gut types,” or what treatments might become less risky after knowing which type someone has. Very cool stuff!

  2. 2.   Chris Lindsay Says:
    April 20th, 2011 at 2:29 pm

    Sort of an un-related question…can you measure and compare organisms’ gut bacteria with other organisms (of a different species) to determine evolutionary relatedness?

  3. 3.   Ed Yong Says:
    April 20th, 2011 at 2:57 pm

    @Robert S-R – Yeah, those are the questions that Bork and his crew are asking. Pretty cool, no?

    @Chris Lindsay – Sort of. Certainly, the evolutionary relationships of the gut bacteria in great apes accurately recaps the evolution of the apes themselves. I wrote about this last year.

  4. 4.   mark mulligan Says:
    April 21st, 2011 at 8:57 pm

    Interesting speculation: I wonder if this gut biota distinction could have anything to do with original diet: primarily carnivore, primarily herbivore or omnivore.

    Scary follow-up speculation: Could these three categories define/include the political categories of totalitarian-fundamentalist/apolitical-passive/anarchist-humanist? If so, the Nazis will have objective criteria, this time around, by which to identify ubermenschen allies and untermenschen victims, regardless of subjective, erroneous and self-defeating criteria like race, nationality, creed, sex, etc.

    In that case, we are in for a global war of extermination that will make every prior one look like a picnic.

    Just speculations, easily proven or disproved (perhaps regrettably).

  5. 5.   Michael Says:
    April 22nd, 2011 at 12:31 am

    As a pharmacy student I can’t help but wonder what unknown impacts this might have on how medications are absorbed from the gut.

  6. 6.   Yohanan Winogradsky Says:
    April 22nd, 2011 at 9:45 am

    Thank you Ed for this nice piece on the enterotypes paper. I will make the same comment as on Carl’s blog and nytimes article earlier today: your articles on the human microbiome are always very interesting and perfectly translate to the general public what our research focuses on.
    I would like to reproduce below the comment we posted this morning (Paris time) under the New York Times article (currently under moderation).

    The enterotypes paper is the result of a wide European collaboration. The EU-funded Project MetaHIT (metagenomics of the human intestinal tract) is behind the enterotypes discovery. Many fields of expertise, teams, labs, researchers are gathered in order for this collaboration to publish such exciting results. We believe that it is more than normal that the whole consortium be thanked and its name, MetaHIT, put forward.

    Congratulations to all the contributors of this wonderful adventure that is our collaboration! Stay tuned for more, it s only a beginning!

    Visit our website for more information http://www.metahit.eu & Follow us on twitter, @MetaHIT

    Do not hesitate to get in touch with us, we’ll be more than happy to give further details on our activities.

  7. 7.   scilicious Says:
    April 24th, 2011 at 5:12 am

    “Europe is a divided land. For such a relatively small continent, it is split into 50 different countries and its people speak hundreds of languages.”

    Okay that made me blink, because if I didn’t know better my first reaction would have been “Said like a true American”. Not quite a metaphor that sits well with me.

    I suppose they didn’t look at if the enterotype might change with relocation? Or is this even a local thing? I can see the age relation and how it would make sense, but it would be interesting if there are other influences (external ones rather than internal) that could change this balance.

  8. 8.   peatey Says:
    April 25th, 2011 at 4:45 am

    Since fetal gut is pretty sterile, initial-seeding differences would be suspects for this divergence. Makers of yogurt and mead would probably agree with me. Naturally, diet is the candidate variable for the gut biome. My guesses for the 3 groups:

    1. natural delivery birth (mother’s feces)
    2. Caesarean delivery birth (no feces)
    3. breastfed or formula (pure guess)

    I remember reading that gut micro-biomes get transmitted at birth via trace amounts of mother’s feces that newborns ingest (Caesarean births are different story entirely, that article stated).

  9. 9.   Liz Says:
    May 15th, 2011 at 8:48 am

    Please provide more specific information and functional analysis of the 3 types. Which types produce which vitamins, break down which foods, are involved in which reactions, (and as above, medications) etc. Thanks

  10. 10.   Mirna Says:
    August 6th, 2011 at 11:46 pm

    This is an interesting discovery and I wonder about any relationship to eocinophilic esophagitis, which my husband suffers from and probably my children do too.

  11. 11.   Cathy Says:
    February 3rd, 2012 at 7:32 am

    If I had to guess, the disease where everyone shares a biome would be digestive related such as Celiac’s disease.

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