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Not Exactly Rocket Science
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Gut bacteria – fat or thin, family or friends, shared or unique

You are not alone. Even if you’re currently reading this in complete isolation, you are still far from a singular individual. You’re more of a colony – one human, together with microbes in their trillions. For every one of your own genes, your body is also host to thousands of bacterial ones. Some of the most important of these tenants – the microbiota – live in our gut. Their genes, collectively known as our microbiome, provide us with the ability to break down sources of food, like complex carbohydrates, that we would otherwise find completely indigestible.

Peter Turnbaugh from the Washington University School of Medicine has spent his career studying the microbiome. His latest work reveals both tremendous differences and similarities between the bacterial tenants of our digestive systems. Your bowels may be home to very different species of bacteria to mine, but both our sets share a core group of genes.

Turnbaugh likens the situation within our guts to that of islands. Real islands may be home to very different species of animals but all have representatives that perform certain roles; there will always be grazers, predators, insect-eating specialists, fishermen and so on.  Across islands, animals approach a set of core lifestyles in different ways, and so it is with the microbiota – every man is an island, home to unique collections of bacteria that nonetheless carry out some core functions. And the further an person’s microbiota strays from this standard template, the more likely they are to be obese.

Gutbacteria.jpg

The discovery came about through a desire to see how similar the microbiota were between close relatives. Together with a large group of US scientists, Turnbaugh collected stool samples from 154 people to analyse their gut bacteria. The volunteers were broadly representative of the local population, had a range of different weights, and had not taken any antibiotics for at least half a year.

They included 54 pairs of twins, both identical and non-identical, and their mothers. Twins are a common feature of genetic studies – if a trait is strongly influenced by genes, you would expect identical twins, who share 100% of their genes, to be more similar in that trait than non-identical twins, who only share 50% of their genes. Indeed, identical twins have more closely matching BMI values than non-identical ones, and they gain weight after overeating in a more similar way.

Unsurprisingly, Turnbaugh found that the microbiotas of relatives are a closer match than those of unrelated people, even within similar weight categories. The reasons for this are unclear; it wasn’t because they shared a common environment, for twins who lived some distance away were no more dissimilar in their bacterial passengers than those who shared a home. Nor were the similarities driven by genes, for the microbiota of both identical and non-identical twins shared equally strong resemblances.

Relatives aside, individuals had extremely different gut bacteria, with few genetic similarities from person to person. No single species was present in more than 0.5% of the stool samples as a whole, and none were found in all the people involved. These differences between individuals were far greater than changes to any one person’s microbiota over time. Using a second set of samples, collected from the same people two months later, Turnbaugh showed that some bacterial groups had risen to dominance and others had fallen from power, but the players were largely the same.

At the genetic level, things looked quite different. The team took a more detailed look at the microbiomes of six of the families, three lean ones and three obese ones, and they found that the genes within all 18 microbiomes performed remarkably consistent jobs. They even had similar proportions of genes dedicated to different tasks. Although very high proportions were involved in breaking down carbohydrates and proteins, Turnbaugh found a relatively even spread of genes involved in various other ‘metabolic pathways’ – sequences of chemical reactions designed to break down potential nutrients.

The researchers also found membership of the microbiota depends on body weight. Compared to lean people, obese ones had fewer bacteria from the Bacteroidetes group and more from the Actinobacteria group. These results mirror earlier work by Turnbaugh’s group which showed that the Bacteroidetes were relatively rarer in obese mice than lean ones, and that their numbers rose in obese people who lost weight.

A closer look at the genes involved confirmed this analysis. Turnbaugh found about 383 genes that were activated to a greater extent in obese people than in lean ones and while the vast majority of these came from Actinobacteria species, none at all hailed from Bacteroidetes sources.

All in all, the obese twins had a less diverse milieu of gut bacteria  than their leaner peers, which may be due to their comparative dearth of Bacteroidetes members. Turnbaugh compares the bowels of obese people to bodies of water that have been choked by agricultural run-offs. In such water, the bacterial community receives a substantial flood of nutrients, but its diversity plummets as a few species bloom and monopolise the extra energy. So it is with guts that have been flooded with calories.

Reference: Peter J. Turnbaugh, Micah Hamady, Tanya Yatsunenko, Brandi L. Cantarel, Alexis Duncan, Ruth E. Ley, Mitchell L. Sogin, William J. Jones, Bruce A. Roe, Jason P. Affourtit, Michael Egholm, Bernard Henrissat, Andrew C. Heath, Rob Knight, Jeffrey I. Gordon (2008). A core gut microbiome in obese and lean twins Nature DOI: 10.1038/nature07540

More on gut bacteria: Human gut bacteria linked to obesity


An introduction to the microbiome

<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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December 1st, 2008 Tags: Bacteria, bowel, Genetics, gut, microbiome, microbiota, microflora, Obesity, weight
by Ed Yong in Bacteria, Genetics, Medicine & health, Microbiome, Obesity | 7 comments | RSS feed | Trackback >

7 Responses to “Gut bacteria – fat or thin, family or friends, shared or unique”

  1. 1.   Austin Says:
    December 1st, 2008 at 2:52 pm

    Very cool stuff. Does this have ramifications in the burgeoning pro-biotic industry? Would we see an increase in obesity in individuals who, following antibiotic treatment, consume specially cultured yogurt or tablets?

  2. 2.   subramanyam Says:
    December 2nd, 2008 at 2:22 am

    can we add some bacteroidetes stuff to obese people to shed their weight? If so very helpful and interesting.

  3. 3.   Jon D Says:
    December 2nd, 2008 at 10:05 am

    Does the study mention at all how much the microbiome changes in individuals over a long period, say a decade?
    I would imagine that dominant colonies established when the relatives were sharing an environment (when the twins or siblings were children living with their parents) would be a barrier to newcomers finding a niche in their guts when they leave home..

  4. 4.   Ed Yong Says:
    December 2nd, 2008 at 10:20 am

    Jon – not really, 2 months was the maximum time interval they examined. Your point’s a good one though and the authors acknowledge it – they say that their results don’t tell us anything about how the microbiota develop during childhood, and that this is an important remaining question.
    As to practical applications, I don’t know – but I would hazard a guess that our knowledge in this area is too preliminary. There are almost certainly routes for tackling obesity that are already more developed (short of obvious lifestyle changes).

  5. 5.   Mo Says:
    December 2nd, 2008 at 1:07 pm

    That micrograph brought back horrible repressed memories of my short time as a science teacher – I used it in a PowerPoint for a Year 8 lesson on microbes.

  6. 6.   Weekly Round Up November 10 – 2010 | Personal Patterns Says:
    November 10th, 2010 at 6:54 am

    [...] Gut bacteria change the sexual preferences of fruit flies – So what? Well, considering we have more or less the same kind of digestive system, it’s always better to know what’s going on down there. Read more: You are what you eat – how your diet defines you in trillions of ways & Gut bacteria – fat or thin, family or friends, shared or unique. [...]

  7. 7.   Weekly Round Up November 10 – 2010 | Connect the Dots Says:
    January 15th, 2011 at 2:36 pm

    [...] Gut bacteria change the sexual preferences of fruit flies – So what? Well, considering we have more or less the same kind of digestive system, it’s always better to know what’s going on down there. Read more: You are what you eat – how your diet defines you in trillions of ways & Gut bacteria – fat or thin, family or friends, shared or unique. [...]

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