http://www.scienceda...10420143620.htm
ScienceDaily (Apr. 21, 2011) — In the future, when you walk into a doctor's surgery or hospital, you could be asked not just about your allergies and blood group, but also about your gut type. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and collaborators in the international MetaHIT consortium, have found that humans have three different gut types.
The study, published in Nature, also uncovers microbial genetic markers that are related to traits like age, gender and body-mass index. These bacterial genes could one day be used to help diagnose and predict outcomes for diseases like colo-rectal cancer, while information about a person's gut type could help inform treatment.
We all have bacteria in our gut that help digest food, break down toxins, produce some vitamins and essential amino acids, and form a barrier against invaders. But the composition of that microbial community -- the relative numbers of different kinds of bacteria -- varies from person to person.
"We found that the combination of microbes in the human intestine isn't random," says Peer Bork, who led the study at EMBL: "our gut flora can settle into three different types of community -- three different ecosystems, if you like."
Bork and colleagues first used stool samples to analyse the gut bacteria of 39 individuals from three different continents (Europe, Asia and America), and later extended the study to an extra 85 people from Denmark and 154 from America. They found that all these cases could be divided into three groups, based on which species of bacteria occurred in high numbers in their gut: each person could be said to have one of three gut types, or enterotypes.
The scientists don't yet know why people have these different gut types, but speculate that they could be related to differences in how their immune systems distinguish between 'friendly' and harmful bacteria, or to different ways of releasing hydrogen waste from cells.
Like blood groups, these gut types are independent of traits like age, gender, nationality and body-mass index. But the scientists did find for example, that the guts of older people appear to have more microbial genes involved in breaking down carbohydrates than those of youngsters, possibly because as we age we become less efficient at processing those nutrients, so in order to survive in the human gut, bacteria have to take up the task.
"The fact that there are bacterial genes associated with traits like age and weight indicates that there may also be markers for traits like obesity or diseases like colo-rectal cancer," Bork says, "which could have implications for diagnosis and prognosis."
If this proves to be the case, when diagnosing or assessing the likelihood of a patient contracting a particular disease, doctors could look for clues not only in the patient's body but also in the bacteria that live in it. And after diagnosis, treatment could be adapted to the patient's gut type to ensure the best results.
http://www.scienceda...10421141632.htm
ScienceDaily (Apr. 22, 2011) — The human gut is filled with 100 trillion symbiotic bacteria -- ten times more microbial cells than our own cells -- representing close to one thousand different species. "And yet, if you were to eat a piece of chicken with just a few Salmonella, your immune system would mount a potent inflammatory response," says Sarkis K. Mazmanian, assistant professor of biology at the California Institute of Technology (Caltech).
Salmonella and its pathogenic bacterial kin don't look that much different from the legion of bacteria in our gut that we blissfully ignore, which raises the question: What decides whether we react or don't? Researchers have pondered this paradox for decades.
In the case of a common "friendly" gut bacterium, Bacteroides fragilis, Mazmanian and his colleagues have figured out the surprising answer: "The decision is not made by us," he says. "It's made by the bacteria. Since we are their home, they hold the key to our immune system."
What's more, the bacteria enforce their "decision" by hijacking cells of the immune system, say Mazmanian and his colleagues, who have figured out the mechanism by which the bacteria accomplish this feat -- and revealed an explanation for how the immune system distinguishes between beneficial and pathogenic organisms.
In addition, the work, described in the April 21 issue of Science Express, "suggests that it's time to reconsider how we define self versus non-self," Mazmanian says.
Like other commensal gut bacteria -- those that provide nutrients and other benefits to their hosts, without causing harm -- B. fragilis was thought to live within the interior of the gut (the lumen), and thus far away from the immune system. "The dogma is that the immune system doesn't respond to symbiotic bacteria because of immunological ignorance," Mazmanian explains. "If we can't see them, we won't react to them."
But using a technique called whole-mount confocal microscopy to study the intestines of mice, he and his colleagues found that the bacteria actually live in a unique ecological niche, deep within the crypts of the colon, "and thus in intimate contact with the gut mucosal immune system," he says.
"The closeness of this association highlights that an active communication is occurring between the bacteria and their host," says Caltech postdoctoral scholar June L. Round.
From that vantage point, the bacteria are able to orchestrate control over the immune system -- and, specifically, over the behavior of immune cells known as regulatory T cells, or Treg cells. The normal function of Treg cells is to prevent the immune system from reacting against our own tissues, by shutting down certain immune responses; they therefore prevent autoimmune reactions (which, when uncontrolled, can lead to diseases such as multiple sclerosis, type 1 diabetes, lupus, psoriasis, and Crohn's disease).
Bacteroides fragilis has evolved to produce a molecule that tricks the immune system into activating Treg cells in the gut, but in this case, Mazmanian says, "the purpose is to keep the cells from attacking the bugs. Beautiful, right?"
In their Science paper, Mazmanian and colleagues describe the entire molecular pathway that produces this effect. It starts with the bacteria producing a complex sugar molecule called polysaccharide A (PSA). PSA is sensed by particular receptors, known as Toll-like receptors, on the surfaces of Treg cells, thus activating those cells specifically. In response, Treg cells suppress yet another type of cell, the T helper 17 (Th17) cells. Normally, Th17 cells induce pro-inflammatory responses -- those that would result, for example, in the elimination of foreign bacteria or other pathogens from the body. By shutting those cells down, B. fragilis gets a free pass to colonize the gut. "Up until now, we have thought that triggering of Toll-like receptors resulted solely in the induction of pathways that eliminate bacteria," says Round. "However, our studies suggest that multiple yet undiscovered host pathways allow us to coexist with our microbial partners."
When Mazmanian and his colleagues blocked this mechanism -- by removing the PSA molecule, by removing the Toll-like receptor for PSA, or by eliminating the Treg cells themselves -- the bacteria were attacked by the immune system and expelled. "They can no longer co-opt the immune system into inducing an anti-inflammatory response, so the formerly benign bacterium now looks like a pathogen," he says, "although the bug itself is exactly the same."
"Our immune system arose in the face of commensal colonization and thus likely evolved specialized molecules to recognize good bacteria," says Round. Mazmanian suspects that genetic mutations in these pathways could be responsible for certain types of immune disorders, including inflammatory bowel disease: "The question is, do patients get sick because they are rejecting bacteria they shouldn't reject?"
On a more philosophical level, Mazmanian says, the findings suggest that our concept of "self" should be broadened to include our many trillions of microbial residents. "These bacteria live inside us for our entire lives, and they've evolved to look and act like us, as part of us," he says. "As far as our immune system is concerned, the molecules made by gut bacteria should be tolerated similarly to our own molecules. Except in this case, the bacteria 'teaches' us to tolerate them, for both our benefit and theirs."
The work was supported by the National Institutes of Health, the Damon Runyon Cancer Research Foundation, and the Crohn's and Colitis Foundation of America.
http://consumer.heal....asp?AID=652138
Gut Bacteria Falls Into Three Major Types
Every human appears to have a distinct intestinal ecosystem, European researchers report
By Jenifer Goodwin
HealthDay Reporter
THURSDAY, April 21 (HealthDay News) -- Just like eye color or blood type, the bacteria that flourish in the gut can also be used to categorize humans, new research finds.
European researchers have determined that there are three distinct types of microscopic ecosystems that exist in the human intestine. What differentiates each type is which species of microbes are present and which are the most abundant, researchers said.
Although there's far more to learn about what those microbes do, researchers say your bacterial type may tell a whole lot about you, including how you metabolize food, how you synthesize vitamins and how you might respond to certain medications.
"We think humans can be categorized based on the micro-composition in their gut," said study co-author Manimozhiyan Arumugam, a research scientist at the European Molecular Biology Laboratory in Heidelberg, Germany. "We also have reasons to believe these are not specific to any continent, country, ethnicity or any other obvious factor."
The human gut is host to an estimated 500 to 1,000 species of bacteria, Arumugam said. Those species compete and cooperate with each other in microscopic ecosystems that remain relatively stable in a balanced, symbiotic relationship with the host -- the human body.
"They are not working alone, they have to work as a community," Arumugam said. "And they have to adapt to the host, such as what we eat."
In the study, published in the April 20 issue of Nature, researchers took stool samples of 22 people from four European countries (Denmark, France, Italy and Spain), extracted the DNA and determined which species of bacteria resided there. They combined their data with the results of earlier data on the gut microbes of 13 people from Japan and two Americans. They then added data from another 85 Danish people and 154 Americans.
Their analysis showed that the microbiota could be grouped into three categories. People with type 1, for example, had high levels of the bacteria Bacteroides. In type 2, Bacteroides levels were lower, but the Prevotella was prevalent. Ruminococcus was a big factor in the third enterotype.
"In the data sets we looked at, we found three types. Would it remain only three if you sampled 100,000 people? We don't know," Arumugam said. "It could also be that maybe these enterotypes could be refined more and that there are subtypes."
Since researchers began to understand that gut microbes play a significant -- and underestimated -- role in human health, one question that's been vexing the field is just how many versions of intestinal microbiota there are, said Justin Sonnenburg, an assistant professor of microbiology and immunology at Stanford University School of Medicine.
If there were an infinite number of variations, then using the information in the real world would be impossibly complex, Sonnenburg added.
"There's been this increasing realization over the past several years that the microbes that live in and upon us are wired into many facets of our biology, and it's also becoming clear that these microbes are going to be a major determinant of variation between individuals, both in relationship to our health, predisposition to disease, progression of diseases and how they should be treated therapeutically," he said.
But by identifying the three types, the new research represents a significant breakthrough, he added.
"This paper really makes a huge leap in establishing that this variation is not a continual and infinite, but that there these finite enterotypes," Sonnenburg said.
Think of it like eye color, Sonnenberg added. There's brown, green, blue, hazel and a perhaps a few other variations, but there is no purple, chartreuse or other colors.
The researchers said they had found no evidence that such characteristics as age, gender or body weight correlated to the gut microbe types.
However, looking across the entire sample, age, gender and body weight did correlate with certain genetic markers in the bacteria, hinting that it may be possible to eventually use such information to diagnose disease or determine who is likely to get diseases, Arumugam said.
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