ideas of the microbiome and the virome...,

Sciencemag | Humans have been doing battle with bacteria since the 1800s, thwarting disease with antibiotics, vaccines, and good hygiene with mixed success. But in 2000, Nobel laureate Joshua Lederberg called for an end to the “We good; they evil” thinking that has fueled our war against microbes. “We should think of each host and its parasites as a superorganism with the respective genomes yoked into a chimera of sorts,” he wrote in Science in 2000.

His comments were prescient. This past decade has seen a shift in how we see the microbes and viruses in and on our bodies. There is increasing acceptance that they are us, and for good reason. Nine in 10 of the cells in the body are microbial. In the gut alone, as many as 1000 species bring to the body 100 times as many genes as our own DNA carries. A few microbes make us sick, but most are commensal and just call the human body home. Collectively, they are known as the human microbiome. Likewise, some viruses take up residence in the body, creating a virome whose influence on health and disease is just beginning to be studied.

Their genes and ours make up a metagenome that keeps the body functioning. This past decade we've begun to see how microbial genes affect how much energy we absorb from our foods and how microbes and viruses help to prime the immune system. Viewing the human and its microbial and viral components as intimately intertwined has broad implications. As one immunologist put it, such a shift “is not dissimilar philosophically from the recognition that the Earth is not the center of the solar system.”

This appreciation has dawned gradually, as part of a growing recognition of the key role microbes play in the world. Microbiologists sequencing DNA from soil, seawater, and other environments have discovered vast numbers of previously undetected species. Other genomics research has brought to light incredible intimacies between microbes and their hosts—such as a bacterium called Buchnera and the aphids inside which it lives. A study in 2000 found that each organism has what the other lacks, creating a metabolic interdependency.

One of the first inklings that microbiologists were missing out on the body's microbial world came in 1999, when David Relman of Stanford University in Palo Alto, California, and colleagues found that previous studies of bacteria cultured from human gums had seriously undercounted the diversity there. Turning to samples taken from the gut and from stools, the researchers identified 395 types of bacteria, two-thirds of them new to science.

In 2006, Steven Gill of the University at Buffalo in New York and colleagues did a metagenomics study of the gut, analyzing all the genes they could find in the 78 million bases sequenced. They found metabolic genes that complemented the human genome, including ones that break down dietary fiber, amino acids, or drugs, and others that produce methane or vitamins. This and a more comprehensive survey in 2010 by Jun Wang of BGI-Shenzhen in China and colleagues provided support for the concept of the microbe-human superorganism, with a vast genetic repertoire. Now, large-scale studies have surveyed the microflora in the gut, skin, mouth, nose, and female urogenital tract. The Human Microbiome Project has sequenced 500 relevant microbial genomes out of a planned 3000.

Some of these microbes may play important roles in metabolic processes. In 2004, a team led by Jeffrey Gordon of Washington University School of Medicine in St. Louis, Missouri, found that germ-free mice gained weight after they were supplied with gut bacteria—evidence that these bacteria helped the body harvest more energy from digested foods. Later studies showed that both obese mice and obese people harbored fewer Bacteroidetes bacteria than their normal-weight counterparts.

The microbiome is also proving critical in many aspects of health. The immune system needs it to develop properly. What's more, to protect themselves inside the body, commensal bacteria can interact with immune cell receptors or even induce the production of certain immune system cells. One abundant gut bacterium, Faecalibacterium prausnitzii, proved to have anti-inflammatory properties, and its abundance seems to help protect against the recurrence of Crohn's disease. Likewise, Sarkis Mazmanian of the California Institute of Technology in Pasadena showed that the human symbiont Bacteroides fragilis kept mice from getting colitis. And inserting bacteria isolated from healthy guts restored the microbial communities, curing chronic diarrhea in a patient infected with Clostridium difficile.

Herbert Virgin of Washington University School of Medicine finds a similar role for the virome. In mice, his team found that dormant herpesviruses revved up the immune system just enough to make the mice less susceptible to certain bacterial infections.

The ideas of a microbiome and a virome didn't even exist a decade ago. But now researchers have reason to hope they may one day manipulate the body's viral and microbial inhabitants to improve health and fight sickness.

genetic engineering of space travelers

Video - Twilight Zone Episode Third From the Sun

LiveScience | NASA's human spaceflight program might take some giant leaps forward if the agency embraces genetic engineering techniques more fully, according to genomics pioneer J. Craig Venter.

The biologist, who established the J. Craig Venter Institute that created the world's first synthetic organism earlier this year, told a crowd here Saturday (Oct. 30) that human space exploration could benefit from more genetic screening and genetic engineering. Such efforts could help better identify individuals most suited for long space missions, as well as make space travel safer and more efficient, he said.

"I think this could change the shape of what NASA does, if you make the commitment to do it," said Venter, who led a team that decoded the human genome a decade ago. Venter spoke to a group of scientists and engineers who gathered at NASA's Ames Research Center for two different meetings: a synthetic biology workshop put on by NASA, and Space Manufacturing 14: Critical Technologies for Space Settlement, organized by the nonprofit Space Studies Institute.

Astronauts with the right (genetic) stuff

Genetics techniques could come in extremely handy during NASA's astronaut selection process, Venter said. The space agency could screen candidates for certain genes that help make good spaceflyers — once those genes are identified, he added.

Genes that encode robust bone regeneration, for example, would be a plus, helping astronauts on long spaceflights battle the bone loss that is typically a major side effect of living in microgravity. Also a plus for any prospective astronaut: genes that code for rapid repair of DNA, which can be damaged by the high radiation levels in space.

Genetic screening would be a natural extension of what NASA already does — it would just add a level of precision, according to Venter.

"NASA's been doing genetic selection for a long time," he said. "You just don't call it that."

Last summer, the agency chose just nine astronaut candidates — out of a pool of 3,500 — for its rigorous astronaut training program based on a series of established spaceflight requirements and in-depth interviews.

A new microbiome
At some point down the road, NASA could also take advantage of genetic engineering techniques to make long space journeys more efficient and easier on astronauts, Venter said.

As an example, he cited the human microbiome, the teeming mass of microbes that live on and inside every one of us. Every human body hosts about 100 trillion microbes — meaning the bugs outnumber our own cells by a factor of at least 10 to one.

While humans only have about 20,000 genes, our microbiome boasts a collective 10 million or so, Venter said. These microbes provide a lot of services, from helping us digest our food to keeping our immune system's inflammation response from going overboard.

With some tailoring, the microbiome could help us out even more, according to Venter.

"Why not come up with a synthetic microbiome?" he asked.

Theoretically, scientists could engineer gut microbes that help astronauts take up nutrients more efficiently. A synthetic microbiome could also eliminate some pathogens, such as certain bacteria that can cause dental disease. Other tweaks could improve astronauts' living conditions, and perhaps their ability to get along with each other in close quarters.

Body odor is primarily caused by microbes, Venter said. A synthetic microbiome could get rid of the offenders, as well as many gut microbes responsible for excessive sulfur or methane production. Fist tap Nana.

a universe of us

NYTimes | We think of ourselves as individuals — perhaps, in philosophical moments, as the merger of body and soul. Most of us are barely aware of the estimated 10 trillion individual cells that make up the human body or of the 100 trillion or more bacteria that live collaboratively and benignly within and upon us. Whatever else we are, we are also a complex ecosystem, a habitat.

Scientists now have discovered another realm within our habitat — the virome, a large community of viruses. These are not the viruses that make us sick. These are an integral part of the microbiotic universe that makes us healthy.

In a recent paper in Nature, a team led by Jeffrey Gordon, a microbiologist at Washington University, reports that each of us has, so to speak, a viral identity — a pattern of viral DNA that is highly stable and highly distinct, even among closely related humans. This is unlike bacterial communities, which tend to evolve over time and to be similar among family members.

This discovery is part of a rapidly growing interest in the microbiome — an effort to understand the diversity and complexity of the trillions of organisms living within each of us. The basic exploratory technique is broad-scale DNA sequencing of the genetic contents of the human gut. The result is a significantly different view of who we are.

We are not just the expression of an individual human genome. We are, as Dr. Gordon writes, “a genetic landscape,” a collective of genomes of hundreds of different species all working together — in ways that leave our minds mysteriously free to focus on getting our bodies to the office and wondering what’s for lunch.

microbiomes-R-us

NYTimes | In 2008, Dr. Khoruts, a gastroenterologist at the University of Minnesota, took on a patient suffering from a vicious gut infection of Clostridium difficile. She was crippled by constant diarrhea, which had left her in a wheelchair wearing diapers. Dr. Khoruts treated her with an assortment of antibiotics, but nothing could stop the bacteria. His patient was wasting away, losing 60 pounds over the course of eight months. “She was just dwindling down the drain, and she probably would have died,” Dr. Khoruts said.

Dr. Khoruts decided his patient needed a transplant. But he didn’t give her a piece of someone else’s intestines, or a stomach, or any other organ. Instead, he gave her some of her husband’s bacteria.

Dr. Khoruts mixed a small sample of her husband’s stool with saline solution and delivered it into her colon. Writing in the Journal of Clinical Gastroenterology last month, Dr. Khoruts and his colleagues reported that her diarrhea vanished in a day. Her Clostridium difficile infection disappeared as well and has not returned since.

The procedure — known as bacteriotherapy or fecal transplantation — had been carried out a few times over the past few decades. But Dr. Khoruts and his colleagues were able to do something previous doctors could not: they took a genetic survey of the bacteria in her intestines before and after the transplant.

Before the transplant, they found, her gut flora was in a desperate state. “The normal bacteria just didn’t exist in her,” said Dr. Khoruts. “She was colonized by all sorts of misfits.”

Two weeks after the transplant, the scientists analyzed the microbes again. Her husband’s microbes had taken over. “That community was able to function and cure her disease in a matter of days,” said Janet Jansson, a microbial ecologist at Lawrence Berkeley National Laboratory and a co-author of the paper. “I didn’t expect it to work. The project blew me away.”

Scientists are regularly blown away by the complexity, power, and sheer number of microbes that live in our bodies. “We have over 10 times more microbes than human cells in our bodies,” said George Weinstock of Washington University in St. Louis. But the microbiome, as it’s known, remains mostly a mystery. “It’s as if we have these other organs, and yet these are parts of our bodies we know nothing about.”

gut bacteria are what we eat

The Scientist | Japanese people regularly consume sushi wrapped in seaweed, which carries with it marine bacteria that produce porphyranases. "It was directly obvious for us that this was horizontal gene transfer from the ocean to the Japanese gut," Hehemann said. "As far as I know, there has not before been an example of horizontal gene transfer between different ecosystems."

In a commentary accompanying the study, Sonnenburg compared the gene transfer event to giving human gut bacteria a "new set of utensils" -- likely providing them the ability to digest specific foods prevalent in different regional diets. "I think there's a good bet that you'll see diet match microbiota functionality over and over and over again," he said. "That's exactly what we see in this study."

But the food purification and sterilization techniques commonly used throughout the industrialized world might affect the environmental tuning of the human gut biome function suggested by the study, Sonnenburg added. Removing many harmful bacteria from foods has dramatically reduced food-borne diseases in recent decades, he said, "but I think there's a likely cost -- the loss of microbes that are not harmful." Such microbes may transfer seemingly beneficial genes to the gut biome, increasing its ability to adapt to changes in diet, as well as fine-tune the immune system, such that "if you begin to eradicate microbes with which we have coevolved, that has the potential [to disrupt] homeostasis," Sonnenburg said.

"It shows how we rely on biodiversity that is surrounding us," Hehemann agreed. "Maybe that's the natural way -- that there is a frequent update of our gut microbiome [through] gene transfer to increase gene diversity. Obviously when we eat these highly processed foods, that's not going to happen."

How exactly this gene transfer helps the host, however, is still unclear, said Hehemann, who is currently looking into the benefits porphyranase genes provide gut bacteria in his new lab at the University of Victoria in British Columbia, Canada. It's possible that when the bacteria break down marine algae polysaccharides, it benefits the host through the production of short chain fatty acids, the end product of bacterial metabolism, which can be taken up by the host in the form of calories, Sonnenburg said. "Those are calories that, in the absence of this capability, go totally unrealized."

gut harbors antibiotic resistance

The Scientist | The millions of microbes that crowd the human intestinal tract are teeming with new antibiotic resistance genes that could jump to disease-causing pathogens, according to researchers from Harvard University.

They found more than 90 undiscovered bacterial genes capable of conferring antibiotic resistance hiding in microbes harvested from two healthy adults. They report their findings in Science today (August 27).

"I thought this was an incredibly cool story," Gerry Wright, McMaster University chemical biologist, told The Scientist. "It tells you just how ignorant we are of microbial ecology."

Wright, director of McMaster's Michael G. DeGroote Institute for Infectious Disease Research, said that the findings raise several key questions. "If there's so much resistance out there, how come [antibiotics] work at all?" asked Wright, who was not involved with the study. "It either means that we really don't understand how antibiotics work or we really don't understand how microbes work."

This lack of understanding is underscored by the fact that humans have exposed their bodies to a potentially dangerous flood of antibiotics -- directly in medicines and indirectly through agriculture and cleaning products -- for decades. This exposure has likely selected for the newly discovered antibiotic resistance genes in our internal microbiome, according to lead author Morten Sommer, a postdoc in Harvard geneticist George Church's lab. "And that could be a problem when the microbiome interacts with disease-causing microbes," he told The Scientist.

subreality mainstreamed?

NYTimes | This week, the 40th anniversary of the first moon landing, there’s much talk of exploring other worlds. Which is exciting and grand; such is the stuff that dreams are made on. Yet we don’t need to go abroad to find amazing new life forms. We just need to look at the palms of our hands, the tips of our fingers, the contents of our guts.

The typical human is home to a vast array of microbes. If you were to count them, you’d find that microbial cells outnumber your own by a factor of 10. On a cell-by-cell basis, then, you are only 10 percent human. For the rest, you are microbial. (Why don’t you see this when you look in the mirror? Because most of the microbes are bacteria, and bacterial cells are generally much smaller than animal cells. They may make up 90 percent of the cells, but they’re not 90 percent of your bulk.)

This much has been known for a long time. Yet it’s only now, with the revolution in biotechnology, that we’re able to do detailed studies of which microbes are there, which genes they have, and what they’re doing. We’re just at the start, and there are far more questions than answers. But already, the results are astonishing, and the implications profound.

Even on your skin, the diversity of bacteria is prodigious. If you were to have your hands sampled, you’d probably find that each fingertip has a distinct set of residents; your palms probably also differ markedly from each other, each home to more than 150 species, but with fewer than 20 percent of the species the same. And if you’re a woman, odds are you’ll have more species than the man next to you. Why should this be? So far, no one knows.

But it’s the bacteria in the digestive tract, especially the gut, that intrigue me most. Many of these appear to be true symbionts: they have evolved to live in guts and (as far as we know) are not found elsewhere. In providing their habitat — a constant temperature, some protection from hostile lifeforms and regular influxes of food — we are as essential to them as they are to us.

And they definitely are essential to us. Gut bacteria play crucial roles in digesting food and modulating the immune system. They make small molecules that we need in order for our enzymes to work properly. They interact with us, altering which of our genes get turned on and off in cells in the intestinal walls. Some evidence suggests that they are essential for the building of a normal heart. Finally, it seems likely that gut bacteria will turn out to affect appetite, as well as other aspects of our behavior, though no one has shown this yet. (Imagine the plea: I’m sorry, sir, my microbes made me do it.)

Together, your gut microbes provide you with a pool of genes far larger than that found in the human genome. Indeed, the gut “microbiome,” as it is known, is thought to contain at least 100 times more genes than the human genome. Moreover, whereas humans are extremely similar to one another at the level of the genome, the microbiome appears to differ markedly from one person to the next.

What determines these differences? Good question. Diet has some effect: a diet rich in sugars and fats reduces the diversity of gut bacteria, and shifts the balance towards those that are more efficient at extracting energy. Start eating more plants and you can shift the balance back, and increase the diversity of your gut microbes. Your own genetic background may play a role as well, though we are far from understanding how, or how much. It probably also matters which other microbes are present: as in any ecosystem, relationships among different inhabitants are likely to be complex.

(At this point, I’d like to introduce a caveat. We know that the diversity of microbial species differs between your gut and mine, and that the less related we are, the more that will be true. Family members tend to have more similar gut microbes than nonrelatives, and preliminary evidence suggests that geography matters, too. So the gut microbes of people in China are different from those of people in the United States — though whether this is due to diet, human genes or geography is entirely unknown. But despite this variation at the species level, we don’t yet know how much variation there is at the genetic level. It may be that different sets of gut microbes provide broadly equivalent sets of genes.)

Naturally, a huge effort is now under way to see whether differences in gut bacteria are responsible for differences in health. But what interests me most about all this is that it suggests another mode of human evolution. Bacteria evolve quickly: they can go through many thousands of generations for every human one.

This has two potential consequences. First, during your lifetime, your bacteria can change their genes even though you cannot change yours. (You do have some flexibility: your immune system has a built-in capacity to change.) It may be that gut bacteria evolve in response to short-term changes in the environment, especially exposure to food-borne diseases. They may thus act as an evolving supplement to the immune system.

The second potential consequence is further reaching. Because bacteria can evolve so fast, it may be that some of what we think of as human evolution — like the ability to digest new diets that accompanied the invention of agriculture — is actually bacterial evolution. We know that hostile bacteria — those that cause diseases in ourselves and our domestic plants and animals — have undergone dramatic genetic changes in the last 10,000 years. Perhaps our friendly bacteria have, too.

are we organisms or living ecosystems?

SeedMagazine | To find a biological answer to the question “Who are we?” we might look to the human genome. Certainly, when the Human Genome Project first produced a draft of the 3 billion-base-pair sequence, it was touted as a blueprint for human life. Less than a decade later, however, most experts recognize that our genomes capture only a part of who we are. Researchers have become aware, for example, of the influence of epigenetic phenomena — imprinting, maternal effects, and gene silencing, among others — in determining how genetic material is ultimately expressed. Now comes the notion that the genomes of microbes within us must also be considered. Our bodies are, after all, composites of human and bacterial cells, with microbes together contributing at least 1,000 times more genes to the whole. As we discover more and more roles that microbes play, it has become impossible to ignore the contribution of bacteria to the pool of genes we define as ourselves. Indeed, several scientists have begun to refer to the human body as a “superorganism” whose complexity extends far beyond what is encoded in a single genome.

The physiology of a superorganism would likely look very different from traditional human physiology. There has been a great deal of research into the dynamics of communities among plants, insect colonies, and even in human society. What new insights could we gain by applying some of that knowledge to the workings of communities in our own bodies? Certain body functions could be the result of negotiations between several partners, and diseases the result of small changes in group dynamics — or of a breakdown in communication between symbiotic partners.

Recently, for instance, evidence has surfaced that obesity may well include a microbial component. In ongoing work that is part of the Human Microbiome Project, researchers in Jeffrey Gordon’s lab at the Washington University School of Medicine in St. Louis showed that lean and obese mice have different proportions of microbes in their digestive systems. Bacteria in the plumper rodents, it seemed, were better able to extract energy from food, because when these bacteria were transferred into lean mice, the mice gained weight. The same is apparently true for humans: In December Gordon’s team published findings that lean and obese twins — whether identical or fraternal — harbor strikingly different bacterial communities. And these bacteria, they discovered, are not just helping to process food directly; they actually influence whether that energy is ultimately stored as fat in the body.

Even confined in their designated body parts, microbes exert their effects by churning out chemical signals for our cells to receive. Jeremy Nicholson, a chemist at Imperial College of London, has become a champion of the idea that the extent of this microbial signaling goes vastly underappreciated. Nicholson had been looking at the metabolites in human blood and urine with the hope of developing personalized drugs when he found that our bodily fluids are filled with metabolites produced by our intestinal bacteria. He now believes that the influence of gut microbes ranges from the ways in which we metabolize drugs and food to the subtle workings of our brain chemistry.

Scientists originally expected that the communication between animals and their symbiotic bacteria would form its own molecular language. But McFall-Ngai, an expert on animal-microbe symbiosis, says that she and other scientists have instead found beneficial relationships involving some of the same chemical messages that had been discovered previously in pathogens. Many bacterial products that had been termed “virulence factors” or “toxins” turn out to not be inherently offensive signals; they are just part of the conversation between microbe and host. The difference between our interaction with harmful and helpful bacteria, she says, is not so much like separate languages as it is a change in tone: “It’s the difference between an argument and a civil conversation.” We are in constant communication with our microbes, and the messages are broadcast throughout the human body.

Human Microbiome Project

Now I know that before I even get started here, nobody read the Oxygen Wars, nobody read Gould's Planet of the Bacteria - and nobody read Wizardology 101 so the noodle-baking I really want to put on you - is only going to come out half-baked - if it gets baked any at all.

Be that as it may, I will continue scattering bread crumbs in hopes that somebody attending to this peculiar web log will connect them all up and go AHHH!!!!!

At the end of the day - all it is - is a different angle of approach or perspective from which to view and consider the affairs in which it is broadly and uncritically believed and accepted that we are the agents. What pipsqueak arrogance leads us to conclude, believe, and act as if it were natural and theological law that we are the fundamental units of selection, the sine qua non and center of the implicate order of creation?

Gut Reaction;

For the first time, scientists have defined the collective genome of the human gut, or colon. Up to 100 trillion microbes, representing more than 1,000 species, make up a motley "microbiome" that allows humans to digest much of what we eat, including some vitamins, sugars, and fiber.

In a study published in the June 2 issue of Science, scientists at The Institute for Genomic Research (TIGR) and their colleagues describe and analyze the colon microbiome, which includes more than 60,000 genes--twice as many as found in the human genome. Some of these microbial genes code for enzymes that humans need to digest food, suggesting that bacteria in the colon co-evolved with their human host, to mutual benefit.

"The GI tract has the most abundant, diverse population of bacteria in the human body," remarks lead author Steven Gill, a molecular biologist formerly at TIGR and now at the State University of New York in Buffalo. "We're entirely dependent on this microbial population for our well-being. A shift within this population, often leading to the absence or presence of beneficial microbes, can trigger defects in metabolism and development of diseases such as inflammatory bowel disease."

The Human Microbiome Project;

Within the body of a healthy adult, microbial cells are estimated to outnumber human cells by a factor of ten to one. These communities, however, remain largely unstudied, leaving almost entirely unknown their influence upon human development, physiology, immunity, and nutrition. To take advantage of recent technological advances and to develop new ones, the NIH Roadmap has initiated the Human Microbiome Project (HMP) with the mission of generating resources enabling comprehensive characterization of the human microbiota and analysis of its role in human health and disease.

Traditional microbiology has focused on the study of individual species as isolated units. However many, if not most, have never been successfully isolated as viable specimens for analysis, presumably because their growth is dependant upon a specific microenvironment that has not been, or cannot be, reproduced experimentally. Among those species that have been isolated, analyses of genetic makeup, gene expression patterns, and metabolic physiologies have rarely extended to inter-species interactions or microbe-host interactions. Advances in DNA sequencing technologies have created a new field of research, called metagenomics, allowing comprehensive examination of microbial communities, even those comprised of uncultivable organisms. Instead of examining the genome of an individual bacterial strain that has been grown in a laboratory, the metagenomic approach allows analysis of genetic material derived from complete microbial communities harvested from natural environments. In the HMP, this method will complement genetic analyses of known isolated strains, providing unprecedented information about the complexity of human microbial communities.

By leveraging both the metagenomic and traditional approach to genomic DNA sequencing, the Human Microbiome Project will lay the foundation for further studies of human-associated microbial communities.

Just a little food for thought...., are you thinking about it yet? (the picture accompanying this post is of a polished stromatolite in the shape of an egg)