Viruses Modulate the Function and Evolution of All Living Things

NYTimes |  High in the Sierra Nevada mountains of Spain, an international team of researchers set out four buckets to gather a shower of viruses falling from the sky.

Scientists have surmised there is a stream of viruses circling the planet, above the planet’s weather systems but below the level of airline travel. Very little is known about this realm, and that’s why the number of deposited viruses stunned the team in Spain. Each day, they calculated, some 800 million viruses cascade onto every square meter of the planet.

Most of the globe-trotting viruses are swept into the air by sea spray, and lesser numbers arrive in dust storms.

“Unimpeded by friction with the surface of the Earth, you can travel great distances, and so intercontinental travel is quite easy” for viruses, said Curtis Suttle, a marine virologist at the University of British Columbia. “It wouldn’t be unusual to find things swept up in Africa being deposited in North America.”

The study by Dr. Suttle and his colleagues, published earlier this year in the International Society of Microbial Ecology Journal, was the first to count the number of viruses falling onto the planet. The research, though, is not designed to study influenza or other illnesses, but to get a better sense of the “virosphere,” the world of viruses on the planet.

Generally it’s assumed these viruses originate on the planet and are swept upward, but some researchers theorize that viruses actually may originate in the atmosphere. (There is a small group of researchers who believe viruses may even have come here from outer space, an idea known as panspermia.)

Whatever the case, viruses are the most abundant entities on the planet by far. While Dr. Suttle’s team found hundreds of millions of viruses in a square meter, they counted tens of millions of bacteria in the same space.

Mostly thought of as infectious agents, viruses are much more than that. It’s hard to overstate the central role that viruses play in the world: They’re essential to everything from our immune system to our gut microbiome, to the ecosystems on land and sea, to climate regulation and the evolution of all species. Viruses contain a vast diverse array of unknown genes — and spread them to other species.

Last year, three experts called for a new initiative to better understand viral ecology, especially as the planet changes. “Viruses modulate the function and evolution of all living things,” wrote Matthew B. Sullivan of Ohio State, Joshua Weitz of Georgia Tech, and Steven W. Wilhelm of the University of Tennessee. “But to what extent remains a mystery.”

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do you ever wonder what your anthropocene antics look like from the bacterial apex?

pnas |  In most ecosystems, microbes are the dominant consumers, commandeering much of the heterotrophic biomass circulating through food webs. Characterizing functional diversity within the microbiome, therefore, is critical to understanding ecosystem functioning, particularly in an era of global biodiversity loss. Using isotopic fingerprinting, we investigated the trophic positions of a broad diversity of heterotrophic organisms. Specifically, we examined the naturally occurring stable isotopes of nitrogen (¹⁵N:¹⁴N) within amino acids extracted from proteobacteria, actinomycetes, ascomycetes, and basidiomycetes, as well as from vertebrate and invertebrate macrofauna (crustaceans, fish, insects, and mammals). Here, we report that patterns of intertrophic ¹⁵N-discrimination were remarkably similar among bacteria, fungi, and animals, which permitted unambiguous measurement of consumer trophic position, independent of phylogeny or ecosystem type. The observed similarities among bacterial, fungal, and animal consumers suggest that within a trophic hierarchy, microbiota are equivalent to, and can be interdigitated with, macrobiota. To further test the universality of this finding, we examined Neotropical fungus gardens, communities in which bacteria, fungi, and animals are entwined in an ancient, quadripartite symbiosis. We reveal that this symbiosis is a discrete four-level food chain, wherein bacteria function as the apex carnivores, animals and fungi are meso-consumers, and the sole herbivores are fungi. Together, our findings demonstrate that bacteria, fungi, and animals can be integrated within a food chain, effectively uniting the macro- and microbiome in food web ecology and facilitating greater inclusion of the microbiome in studies of functional diversity.

N-1 a literal diseased state?

biologydirect |  The variety of parasites that can affect host behavior suggests that the phenomena of parasitic host control might be more common in nature than currently established and could have been overlooked in humans. This warrants a detailed search for parasitic organisms that affect human behavior. One approach to search for “invisible” microbes that influence behavior is by comparing the microbiomes of control subjects and humans that consistently engage in irrational ritualistic behavioral activities, which contribute to the spreading of parasites and infections.

The modern anthropological view on religion is that it is a cultural meme that replicates through social communication [44]. While the meme itself may influence behavior, religious icons are known to be vectors of infectious diseases [45]. Most major religions have rituals that are likely to promote the transmission of infections. This includes circumcision [46], Christian common communion chalice [46], the Hindu ‘side-roll’[46] and Islamic ritual ablution [46] as well as the Hajj congregation in Mecca [47]. For example, the latter is specifically associated with outbreaks of meningococcal disease [48].

Also many religions are centered on sacred relics that are worshiped and frequently kissed by multiple people and thereby can act as vessels for microbial transmission. Crosses, icons, Bible covers are kissed in some denominations of the Christian tradition, the Black Stone (the eastern cornerstone of the Kaaba) is a relic that is kissed by millions of Muslims, kissing of the Wailing Wall is a religious tradition for the Jewish. It is unlikely, but possible that the rejection of condom use, vaccination and use of antibiotics present in some religious cultures, as well as the sacred status of specific domestic animals (possible definitive hosts to the parasites) may also be related to microbial host control. Finally, it has been noted that many parasites eliminate their hosts reproductive potential as they channel all available resources to maximize their own reproductive success [18]. Coincidentally celibacy is commonplace for holy individuals that are most devoted to their faith such as monks or nuns.

Thus it is possible that various religious practices could represent biomemes: manifestations of a symbiosis between informational memes [54] and biological organisms. This concept is somewhat similar to the fictional midichlorians of the Jedi Order from the popular series “Star Wars”[55].

Two particular parts of the human body seem to be most promising for the search of  behavior-altering parasites. First of all, the human gut microbiome may be of interest in light of the microbiome-gut-brain axis concept. Another promising area to search for behavioraltering parasites is the human brain. Several organisms that can bypass the mammalian blood–brain barrier and produce a latent infection without obvious symptoms are currently known. In mice with latent toxoplasmosis, Toxoplasma gondii cysts can be found in various regions of the brain, especially in the olfactory bulb, the entorhinal, somatosensory, motor and orbital, frontal association and visual cortices, the hippocampus and the amygdala [56]. In humans the brain also appears to be an important site for Toxoplasma gondii cyst formation and the parasite is capable of infecting a variety of brain cells, including astrocytes and neurons [57-59].

the business model consists in fleecing credulous geeks with more money than sense...,

discovermagazine |  Full disclosure, I didn’t pay $89 for my sample analysis kit. But if I had, I would have been disappointed. And if I had paid $399 for the five-site kit, I would have been even more so. The amount of readily available information provided little enlightenment about what my internal lurkers meant about me.

To be fair, this is not totally uBiome’s fault, and it’s something they disclose explicitly in the terms of service. We don’t know enough about the microbiome to say, “Too many of X and too little of Y mean Z,” or, “Firmicutes make you fat.” I knew that, and uBiome made very clear that no human should use their service to diagnose themselves or predict their future, and that knowledge of the microbiome is nascent and evolving. But I did expect the comparison tools to have more flexibility.

I could check out how my bacteria’s phyla stood up to those of vegans, paleos, vegetarians, heavy drinkers, weight losers, weight gainers, those on antibiotics, men, and women. But not women on antibiotics. Or vegetarian women who are in their 30s. And I couldn’t compare a level beneath phylum.

My microbiome doesn’t look like vegans’, paleos’, vegetarians’, lushes’, or any of the other groups’, which makes sense given that I’m an individual and don’t strictly fit within those categories. 

However, it also means that my data didn’t provide me much insight. I could download my own raw data and manipulate it, but then I was looking at it in a vacuum, without a set to compare to, so the analysis amounts mostly to, “Hey, look. I have this many of those bacteria. Neat?”

Beyond that, I could see a list of all my bacteria and what percentage of the population they were; which were “most enriched” compared to the aggregate; and which were “most depleted” compared to the aggregate. For some, I could click on their name — digging down from phylum to genus — and learn more about their lives and the effect they might have on mine.

However, many — more than half, if you go all the way to genus — don’t have entries. That’s because science hasn’t figured them out yet. And science will almost certainly figure them out in the future… By which time, however, my microbiome will probably have changed.

Bio Business Model

uBiome bills itself primarily as a citizen science project—your guts in your hands!

transhumans about the bidnis of enginnering biomes, as well...,

MIT |  No matter where you are, you are surrounded by your microbiome—the complex biological system of more than 100 trillion microorganisms on the human body, in airwaves, and in every environment.

“You may not know it, but you’re walking around with two pounds of microbes on you,” says Bernat Olle SM ’05, MBA ’07, PhD ’07. “But only recently have scientists discovered how important and how useful they can be.”

Research in the field of the microbiome is still in its early stages, but it has already shown that microbes play important roles in metabolism, digestion, and even mood. And Olle is one of a growing group of engineers focusing on this area.

“Modern habits have been to clean up and sterilize everything—make it clean as possible,” he says. “But we’re starting to find out this might not be a good idea—and we’re abusing anti-microbial chemicals. These microbial exposures can help develop key human functions.”

Olle is co-founder and COO of Vedanta Biosciences, a Boston-based startup that researches interactions between the human microbiome and the immune system. He spoke to Slice of MIT at the 2015 South by Southwest (SXSW) Interactive, where he was part of a three-person panel that discussed the benefits of microbes and the impact they could have on medicine in the future.

the body's ecosystem

thescientist |  The human body is teeming with microbes—trillions of them. The commensal bacteria and fungi that live on and inside us outnumber our own cells 10-to-1, and the viruses that teem inside those cells and ours may add another order of magnitude. Genetic analyses of samples from different body regions have revealed the diverse and dynamic communities of microbes that inhabit not just the gut and areas directly exposed to the outside world, but also parts of the body that were long assumed to be microbe-free, such as the placenta, which turns out to harbor bacteria most closely akin to those in the mouth. The mouth microbiome is also suspected of influencing bacterial communities in the lungs. Researchers are also examining the basic biology of the microbiomes of the penis, the vagina, and the skin.

“No tissue in the human body is sterile, including reproductive tissues and, for that matter, the unborn child,” Seth Bordenstein, a biologist at Vanderbilt University, says in an e-mail to The Scientist.

Altogether, the members of the human body’s microbial ecosystem make up anywhere from two to six pounds of a 200-pound adult’s total body weight, according to estimates from the Human Microbiome Project, launched in 2007 by the National Institutes of Health (NIH). The gastrointestinal tract is home to an overwhelming majority of these microbes, and, correspondingly, has attracted the most interest from the research community. But scientists are learning ever more about the microbiomes that inhabit parts of the body outside the gut, and they’re finding that these communities are likely just as important. Strong patterns, along with high diversity and variation across and within individuals, are recurring themes in microbiome research. While surveys of the body’s microbial communities continue, the field is also entering a second stage of inquiry: a quest to understand how the human microbiome promotes health or permits disease.

“None of us in the field—and this is true for the gut, this is true for the skin—none of us can actually tell how our experimental observations really relate to human disease, but we’re getting closer to mechanistic insights,” says immunologist Yasmine Belkaid, chief of mucosal immunology at the National Institute of Allergy and Infectious Disease.

microbial colonization...,

thescientist |  Infants start out mostly microbe-free but quickly acquire gut bacteria, which take root in three successive groups. First, Bacilli dominate. Then Gammaproteobacteria surge, followed by Clostridia. But the pace at which these bacterial groups colonize the gastrointestinal tract depends on the time since the babies were conceived, not since when they were born. And time since conception appears to have more of an influence on the infant gut microbiome than other factors, such as exposure to antibiotics, whether babies were born vaginally or by cesarean section, and if they were breastfed. These are a few of the findings from a survey of 922 fecal samples collected from 58 premature babies, published today (August 11) in PNAS.

“It is an interesting study that provides useful data regarding temporal changes in microbial composition in the infant gut that can be mined further,” Shyamal Peddada, a biostatistician at the National Institute of Environmental Health Sciences who was not involved in the study, wrote in an e-mail to The Scientist.

“I think the paper does a nice job of showing that premature babies develop differently from full-term babies . . . it is not just a function of colonization after birth,” Rob Knight from the University of Colorado, Boulder, told The Scientist in an e-mail. “Differences in gut physiology or in the infant immune system could explain this pattern.”

Researchers at the Washington University School of Medicine in St. Louis embarked on this survey in an effort to better understand the role of the microbiota in the development of gut disorders common in premature infants, such as necrotizing enterocolitis. Without first defining the premature infant gut in the absence of gastrointestinal issues, the researchers struggled to identify potentially pathogenic bacterial patterns.

The researchers collected stool samples each time the babies defecated until they were thirty days old, and sampled every third elimination after that. They then sequenced 16S ribosomal RNA genes to identify the bacterial composition of each sample.

voices from within: gut microbes and the central nervous system

springer |  Recent advances in research have greatly increased our understanding of the importance of the gut microbiota. Bacterial colonization of the intestine is critical to the normal development of many aspects of physiology such as the immune and endocrine systems. It is emerging that the influence of the gut microbiota also extends to modulation of host neural development. Furthermore, the overall balance in composition of the microbiota, together with the influence of pivotal species that induce specific responses, can modulate adult neural function, peripherally and centrally. Effects of commensal gut bacteria in adult animals include protection from the central effects of infection and inflammation as well as modulation of normal behavioral responses. There is now robust evidence that gut bacteria influence the enteric nervous system, an effect that may contribute to afferent signaling to the brain. The vagus nerve has also emerged as an important means of communicating signals from gut bacteria to the CNS. Further understanding of the mechanisms underlying microbiome–gut–brain communication will provide us with new insight into the symbiotic relationship between gut microbiota and their mammalian hosts and help us identify the potential for microbial-based therapeutic strategies to aid in the treatment of mood disorders.

missing microbes: conspicuously obvious once the man points it out...,

martinblaser |   From Missing Microbes by Martin J. Blaser, MD. Blaser, former chair of medicine at NYU and president of the Infectious Diseases Society of America, is one of a growing number of medical practitioners and researchers who believe that we are experiencing a growing array of "modern plagues," and that the cause of these plagues is rooted in our "disappearing microbiota":

"Within the past few decades, amid all of [our] medical advances, something has gone terribly wrong. In many different ways we appear to be getting sicker. You can see the headlines every day. We are suffering from a mysterious array of what I call 'modern plagues': obesity, childhood diabetes, asthma, hay fever, food allergies, esophageal reflux and cancer, celiac disease, Crohn's disease, ulcerative colitis, autism, eczema. In all likelihood you or someone in your family or someone you know is afflicted. Unlike most lethal plagues of the past that struck relatively fast and hard, these are chronic conditions that diminish and degrade their victims' quality of life for decades. ...

"The autoimmune form of diabetes that begins in childhood and requires insulin injections (juvenile or Type I diabetes) has been doubling in incidence about every twenty years across the industrialized world. In Finland, where record keeping is meticulous, the incidence has risen 550 percent since 1950. ... But the disease itself has not changed; something in us has changed. Type I diabetes is also striking younger children. The average age of diagnosis used to be about nine. Now it is around six, and some children are becoming diabetic when they are three.

"The recent rise in asthma, a chronic inflammation of the airways, is similarly alarming. One in twelve people (about 25 million or 8 percent of the U.S. population) had asthma in 2009, compared with one in fourteen a decade earlier. Ten percent of American children suffer wheezing, breathlessness, chest tightness, and coughing; black children have it worst: one in six has the disease. Their rate increased by 50 percent from 2001 through 2009. But the rise in asthma has not spared any ethnicity: the rates were initially different in various groups, and all have been rising. ... No economic or social class has been spared.

"Food allergies are everywhere. A generation ago, peanut allergies were extremely rare. ... Ten percent of children suffer from hay fever. Eczema, a chronic skin inflammation, affects more than 15 percent of children and 2 percent of adults in the United States. In industrialized nations, the number of kids with eczema has tripled in the past thirty years. ...

"Why are all of these maladies rapidly rising at the same time across the developed world and spilling over into the developing world as it becomes more Westernized? Can it be a mere coincidenc

e? If there are ten of these modern plagues, are there ten separate causes? That seems unlikely.

"Or could there be one underlying cause fueling all these parallel increases? A single cause is easier to grasp; it is simpler, more parsimonious. But what cause could be grand enough to encompass asthma, obesity, esophageal reflux, juvenile diabetes, and allergies to specific foods, among all of the others? Eating too many calories could explain obesity but not asthma; many of the children who suffer from asthma are slim. Air pollution could explain asthma but not food allergies. ...

"The most popular explanation for the rise in childhood illness is the so-called hygiene hypothesis. The idea is that modern plagues are happening because we have made our world too clean. The result is that our children's immune systems have become quiescent and are therefore prone to false alarms and friendly fire. ...

"We need to look closely at the microorganisms that make a living in and on our bodies, massive assemblages of competing and cooperating microbes known collectively as the microbiome. ... Each of us hosts a ... diverse ecology of microbes that has coevolved with our species over millennia. They thrive in the mouth, gut, nasal passages, ear canal, and on the skin. In women, they coat the vagina. The microbes that constitute your microbiome are generally acquired early in life; surprisingly, by the age of three, the populations within children resemble those of adults. Together, they play a critical role in your immunity as well as your ability to combat disease. In short, it is your microbiome that keeps you healthy. And parts of it are disappearing.

"The reasons for this disaster are all around you, including overuse of antibiotics in humans and animals, Cesarean sections, and the widespread use of sanitizers and antiseptics, to name just a few. ...

"The loss of diversity within our microbiome is far more pernicious [than the overuse of antibiotics and resulting antibiotic resistance]. Its loss changes development itself, affecting our metabolism, immunity, and cognition.

"I have called this process the 'disappearing microbiota.' It's a funny term that does not immediately roll off your tongue, but I believe it is correct. For a number of reasons, we are losing our ancient microbes. This quandary is the central theme of this book. The loss of microbial diversity on and within our bodies is exacting a terrible price. I predict it will be worse in the future. Just as the internal combustion engine, the splitting of the atom, and pesticides all have had unanticipated effects, so too does the abuse of antibiotics and other medical or quasi-medical practices (e.g., sanitizer use).

"An even worse scenario is headed our way if we don't change our behavior. It is one so bleak, like a blizzard roaring over a frozen landscape, that I call it 'antibiotic winter.'"

the quantified microbiome visualization looks strangely like an appflow visualization...,

nationalgeographic |  Some of my friends are sporting wristbands these days that keep track of their bodies. Little computers nestled in these device inside record the steps they take each day, the beats of their heart, the length of their slumbers. At the end of each day, they can sit down at a computer and look at their data arrayed across a screen like a seismogram of flesh.

I got one of these devices as a gift recently. But as much as I enjoy wasting time with technology, I just didn’t care enough to put it on my wrist. I already know that I should run more, walk more, stand more, and avoid sitting in front of monitors more. I don’t need granular data to remind me of that.

But as I read the journal Genome Biology today, I decided that someday I might surrender to the Quantified Self movement. I’ll just have to wait till I can track my trillions of microbes from one day to the next.

Thanks to the falling cost of sequencing DNA, it’s now possible for us to survey the thousands of species that live in our bodies. A couple years ago, for example, I found out that I have 58 species in my bellybutton. But all I knew was that there were 58 species in my bellybutton at one point in time–that moment I swiped a Q-tip around my navel. But everything we know about bacteria tells us that our inner ecosystems can change swiftly. My bellybutton may be remarkably different today than it was when I put a Q-tip in it.

Eric Alm, a biologist at MIT, and a graduate student of his named Lawrence David decided to plumb this change by tracking a year in the life of their microbiomes. Each day, they saved some of their stool, and later, they extracted DNA from it to figure out which species of bacteria were living in their guts. David also spat some of his saliva into a tube each day so that he could compare how his microbiome changed in his gut compared to his mouth.

Even though their study only involved two people, it was still very much a Big Data project. And one of the major challenges of any Big Data project is to visualize the results in a useful way. A number on a wrist watch won’t cut it. Between Alm and David, they and their colleagues identified thousands of species of microbes. Most were rare, while a few hundred made up the majority of bugs in their bodies. Some species showed up briefly and vanished; others lingered all year.

Here’s one way to look at their microbiomes. It shows David’s saliva. Each band represents one of the dominant species (or operational taxonomic units). Species belonging to the same lineage (a phylum) have different shades of the same color.  Fist tap Dale.

biota, diet, brains, power...,

bbc |  I have some startling news: you are not human. At least, by some counts. While you are indeed made up of billions of human cells working in remarkable concert, these are easily outnumbered by the bacterial cells that live on and in you – your microbiome. There are ten of them for every one of your own cells, and they add an extra two kilograms (4.4lbs) to your body. 

Far from being freeloading passengers, many of these microbes actively help digest food and prevent infection. And now evidence is emerging that these tiny organisms may also have a profound impact on the brain too. They are a living augmentation of your body – and like any enhancement, this means they could, in principle, be upgraded. So, could you hack your microbiome to make yourself healthier, happier, and smarter too?

According to John Cryan, this isn’t as far-fetched as it sounds. As a professor of anatomy and neuroscience at University College Cork, he specialises in the relationship between the brain and the gut. One of his early experiments showed the diversity of bacteria living in the gut was greatly diminished in mice suffering from early life stress. This finding inspired him to investigate the connection between the microbiome and the brain.

The bacterial microbiota in the gut helps normal brain development, says Cryan. “If you don’t have microbiota you have major changes in brain structure and function, and then also in behaviour.” In a pioneering study, a Japanese research team showed that mice raised without any gut bacteria had an exaggerated physical response to stress, releasing more hormone than mice that had a full complement of bacteria. However, this effect could be reduced in bacteria-free mice by repopulating their gut with Bifidobacterium infantis, one of the major symbiotic bacteria found in the gut. Cryan’s team built on this finding, showing that this effect could be reproduced even in healthy mice. “We took healthy mice and fed them Lactobacillus [another common gut bacteria), and we showed that these animals had a reduced stress response and reduced anxiety-related behaviours.” Fist tap Dale.

breath straight kicking like cancer....,

thescientist | Fusobacterium nucleatum is a Gram-negative oral commensal microbe, but it has the potential to become pathogenic, occasionally causing periodontal disease. In October 2011, two separate teams from Canada’s BC Cancer Agency and the Broad Institute in Cambridge showed that the bacterium could also be found in the gut, where its abundance was associated with colorectal cancer. Now, two new studies present functional evidence to help explain how F. nucleatum spurs the development of cancer.

In papers published in Cell Host & Microbe today (August 13), teams led by Harvard Medical School’s Aleksandar Kostic and Case Western Reserve University’s Mara Roxana Rubinstein used a mouse model of intestinal tumorigenesis and human colon cancer cells, respectively, to show that F. nucleatum induces proinflammatory and oncogenic activities that promote the growth of colorectal cancer.

“It is usually impossible to infer whether microbes are causative or opportunistic colonizers without functional studies,” said Robert Holt, who led the BC Cancer Agency team that in 2011 reported an association between F. nucleatum in the gut and colorectal cancer but was not involved in the present studies. “Identifying an infectious origin for disease almost always starts with observing an association between the presence of a microbe and the presence of a particular pathology, but an understanding of causality—or lack thereof—requires the gradual accumulation of experimental and epidemiological evidence,” such as that reported today.

The Washington University School of Medicine’s Gautam Dantas agreed that the new work helps distinguish cause from consequence. “Is an observed altered microbiome state in a diseased individual the cause of the disease, or a symptom?” Dantas, who was not involved in the studies, wrote in an e-mail to The Scientist. The papers published today “report on significant strides towards . . . identifying the mechanisms by which a human commensal bacterium, Fusobacterium nucleatum, promotes colorectal cancer.”

human breath analysis and individual metabolic phenotypes

plosone | The metabolic phenotype varies widely due to external factors such as diet and gut microbiome composition, among others. Despite these temporal fluctuations, urine metabolite profiling studies have suggested that there are highly individual phenotypes that persist over extended periods of time. This hypothesis was tested by analyzing the exhaled breath of a group of subjects during nine days by mass spectrometry. Consistent with previous metabolomic studies based on urine, we conclude that individual signatures of breath composition exist. The confirmation of the existence of stable and specific breathprints may contribute to strengthen the inclusion of breath as a biofluid of choice in metabolomic studies. In addition, the fact that the method is rapid and totally non-invasive, yet individualized profiles can be tracked, makes it an appealing approach.

medical ecology

NYTimes | For a century, doctors have waged war against bacteria, using antibiotics as their weapons. But that relationship is changing as scientists become more familiar with the 100 trillion microbes that call us home — collectively known as the microbiome.

“I would like to lose the language of warfare,” said Julie Segre, a senior investigator at the National Human Genome Research Institute. “It does a disservice to all the bacteria that have co-evolved with us and are maintaining the health of our bodies.”

This new approach to health is known as medical ecology. Rather than conducting indiscriminate slaughter, Dr. Segre and like-minded scientists want to be microbial wildlife managers.

No one wants to abandon antibiotics outright. But by nurturing the invisible ecosystem in and on our bodies, doctors may be able to find other ways to fight infectious diseases, and with less harmful side effects. Tending the microbiome may also help in the treatment of disorders that may not seem to have anything to do with bacteria, including obesity and diabetes.

“I cannot wait for this to become a big area of science,” said Michael A. Fischbach, a microbiologist at the University of California, San Francisco, and an author of a medical ecology manifesto published this month in the journal Science Translational Medicine.

Judging from a flood of recent findings about our inner ecosystem, that appears to be happening. Last week, Dr. Segre and about 200 other scientists published the most ambitious survey of the human microbiome yet. Known as the Human Microbiome Project, it is based on examinations of 242 healthy people tracked over two years. The scientists sequenced the genetic material of bacteria recovered from 15 or more sites on their subjects’ bodies, recovering more than five million genes.

The project and other studies like it are revealing some of the ways in which our invisible residents shape our lives, from birth to death.

A number of recent reports shed light on how mothers promote the health of their children by shaping their microbiomes. In a study published last week in the journal PLoS One, Dr. Kjersti Aagaard-Tillery, an obstetrician at Baylor College of Medicine, and her colleagues described the vaginal microbiome in pregnant women. Before she started the study, Dr. Aagaard-Tillery expected this microbiome to be no different from that of women who weren’t pregnant.

“In fact, what we found is the exact opposite,” she said.

oops, they forgot the breastesses...,

kurzweilai | Some 200 members of the Human Microbiome Project (HMP) Consortium from nearly 80 universities and scientific institutions, organized by the National Institutes of Health, have mapped the normal microbial makeup of healthy humans, producing numerous insights and even a few surprises.

The report on on their five years of research was published Thusday June 14, 2012, in a series of coordinated scientific reports in Nature the PLoS.

Researchers found, for example, that nearly everyone routinely carries pathogens, microorganisms known to cause illnesses.

In healthy individuals, however, pathogens cause no disease; they simply coexist with their host and the rest of the human microbiome, the collection of all microorganisms living in the human body.

Researchers must now figure out why some pathogens turn deadly and under what conditions, likely revising current concepts of how microorganisms cause disease.

“Like 15th century explorers describing the outline of a new continent, HMP researchers employed a new technological strategy to define, for the first time, the normal microbial makeup of the human body,” said NIH Director Francis S. Collins, M.D., Ph.D.

“HMP created a remarkable reference database by using genome sequencing techniques to detect microbes in healthy volunteers. This lays the foundation for accelerating infectious disease research previously impossible without this community resource.”

To define the normal human microbiome, HMP researchers sampled 242 healthy U.S. volunteers (129 male, 113 female), collecting tissues from 15 body sites in men and 18 body sites in women.

Researchers collected up to three samples from each volunteer at sites such as the mouth, nose, skin (two behind each ear and each inner elbow), and lower intestine (stool), and three vaginal sites in women; each body site can be inhabited by organisms as different as those in the Amazon Rainforest and the Sahara Desert.

Historically, doctors studied microorganisms in their patients by isolating pathogens and growing them in culture. This painstaking process typically identifies only a few microbial species, as they are hard to grow in the laboratory. In HMP, researchers purified all human and microbial DNA in each of more than 5,000 samples and analyzed them with DNA sequencing machines.

the wonder of breasts

Guardian | We love breasts, yet can't quite take them seriously. Breasts embarrass us. They're unpredictable. They're goofy. They can turn babies and grown men into lunkheads.

They appear out of nowhere in puberty, they get bigger in pregnancy, they're capable of producing prodigious amounts of milk, and sometimes they get sick. But for such an enormously popular feature of the human race, it's remarkable how little we know about their basic biology.

The urgency to know and understand breasts has never been greater. Modern life has helped many of us live longer and more comfortably. It has also, however, taken a strange toll on our breasts. For one thing, they are bigger than ever. We are sprouting them at younger ages. We are filling them with saline and silicone and transplanted stem cells to change their shape. This year marks the 50th anniversary of the first silicone implant surgery in Houston, Texas.

More tumours form in the breast than in any other organ, making breast cancer the most common malignancy in women worldwide. Its incidence has almost doubled since the 1940s and is still rising.

But breasts are often overlooked, at least for non-cancer scientific research. The Human Microbiome Project, for example, is decoding the microbial genes of every major human gland, liquid and orifice, from the ears to the genitals. It neglected to include breast milk.

I wanted to know more, so I went to the 15th meeting of the International Society for Research in Human Milk and Lactation in Lima. Many attendees were molecular biologists, biochemists or geneticists who are deconstructing milk bit by bit. Until recently, it was thought breast milk had around 200 components. These could be divided into the major ingredients of fats, sugars, proteins and enzymes. But new technologies have allowed researchers to look deeper into each of these categories and discover new ones.

Scientists used to think breast milk was sterile, like urine. But it's more like cultured yoghurt, with lots of live bacteria doing who knows what. These organisms evolved for a reason, and somehow they're helping us out. One leading theory is they act as a vaccine, inoculating the infant gut. A milk sample has anywhere from one to 600 species of bacteria. Most are new to science.

Then there are the sugars. There's a class of them called oligosaccharides, which are long chains of complex sugars. Scientists have identified 140 of them so far, and estimate there are about 200. The human body is full of oligosaccharides, which ride on our cells attached to proteins and lipids. But a mother's mammary gland cooks up a unique batch of "free" or unattached ones and deposits them in milk. These are found nowhere else in nature, and not every mother produces the same ones, since they vary by blood type. Even though they're sugars, the oligosaccharides are, weirdly, not digestible by infants. Yet they are a main ingredient, present in milk in the same percentage as the proteins, and in higher amounts than the fats. So what are they doing there?

They don't feed us, but they do feed many types of beneficial bacteria that make a home in our guts and help us fight infections. In addition to recruiting the good bugs, these sugars prevent the bad bugs from hanging around. "The benefits of human milk are still underestimated," said Lars Bode, an immunobiologist at the University of California, San Diego. "We're still discovering functional components of breast milk."

what bugs are in your gut?

TheScientist | Humans from different cultures and geographic locations differ in the diversity of bacteria in their guts, but the metabolic functions that those microbial communities serve are similar, according to a report out in Nature today (May 9). The findings come from a large-scale sequencing project carried out on 531 samples of human excrement from Africa, South America, and the United States.

“It’s a humungous paper, with multiple key findings,” said food scientist David Mills of the University of California, Davis. “An impressive and complex piece of work,” agreed molecular biologist Jeremy Nicholson of Imperial College, London. Neither researcher participated in the study.

The scale and complexity stem from the research team’s aim of answering a multifaceted question—“What is the degree to which these microbial communities… vary within a person, as a function of postnatal development, physiological status, cultural tradition, and where a person lives,” said geneticist Jeffrey Gordon of the Washington University in St Louis, who led the study.

To this end, the researchers collected samples of feces from villagers in rural Malawi, Amerindians in Amazonian Venezuela, and metropolis-dwelling Americans. They then performed high-throughput sequencing on DNA taken from the samples to determine both the species and strains of microbes present and which microbial genes were most abundant.

The team found a common pattern for how the microbiomes of babies develop in the three countries. “It takes 6 to 9 months to get the first 6 or 700 bugs and then another couple of years to get the adult set,” explained Nicholson. “[Gordon] finds there is the same sort of developmental time span between countries,” he said, “but that the resulting microbiomes are nonetheless distinct between, let’s call it, a third-world population and a westernized population.”

One of the most striking differences was the degree of microbial diversity, with both the Amerindians and Malawians having far greater diversity than the Americans. “But, ironically, [Americans] might have more diversity in terms of the food eaten,” said Mills, which might have been expected to correlate with microbial diversity. Gordon suggested the Westerners’ lack of diversity could result from “our lifestyle, our degree of hygiene, [and] our use of antibiotics,” though further research is needed to test these possibilities.

Despite these differences between the gut microbiomes of the three cultures, there were also striking similarities, said Gordon. For example, “across all three populations, we see this age-dependent change in vitamin biosynthesis,” he said. In infants, gut bacteria tend to carry more copies of genes involved in folate biosynthesis, while the guts of older individuals harbor microbes carrying more genes for folate metabolism. Conversely, genes involved in vitamin B-12 synthesis became more prevalent in the gut microbiome with age.

“What’s really fascinating about those results,” said Mills, “is that it is reflecting what the host needs.”

bacteria divide people into types

NYTimes | In the early 1900s, scientists discovered that each person belonged to one of four blood types. Now they have discovered a new way to classify humanity: by bacteria. Each human being is host to thousands of different species of microbes. Yet a group of scientists now report just three distinct ecosystems in the guts of people they have studied.

Blood type, meet bug type.

“It’s an important advance,” said Rob Knight, a biologist at the University of Colorado, who was not involved in the research. “It’s the first indication that human gut ecosystems may fall into distinct types.”

The researchers, led by Peer Bork of the European Molecular Biology Laboratory in Heidelberg, Germany, found no link between what they called enterotypes and the ethnic background of the European, American and Japanese subjects they studied.

Nor could they find a connection to sex, weight, health or age. They are now exploring other explanations. One possibility is that the guts, or intestines, of infants are randomly colonized by different pioneering species of microbes.

The microbes alter the gut so that only certain species can follow them.

Whatever the cause of the different enterotypes, they may end up having discrete effects on people’s health. Gut microbes aid in food digestion and synthesize vitamins, using enzymes our own cells cannot make.

Dr. Bork and his colleagues have found that each of the types makes a unique balance of these enzymes. Enterotype 1 produces more enzymes for making vitamin B7 (also known as biotin), for example, and Enterotype 2 more enzymes for vitamin B1 (thiamine).

The discovery of the blood types A, B, AB and O had a major effect on how doctors practice medicine. They could limit the chances that a patient’s body would reject a blood transfusion by making sure the donated blood was of a matching type. The discovery of enterotypes could someday lead to medical applications of its own, but they would be far down the road.

“Some things are pretty obvious already,” Dr. Bork said. Doctors might be able to tailor diets or drug prescriptions to suit people’s enterotypes, for example.

Or, he speculated, doctors might be able to use enterotypes to find alternatives to antibiotics, which are becoming increasingly ineffective. Instead of trying to wipe out disease-causing bacteria that have disrupted the ecological balance of the gut, they could try to provide reinforcements for the good bacteria. “You’d try to restore the type you had before,” he said.

Dr. Bork notes that more testing is necessary. Researchers will need to search for enterotypes in people from African, Chinese and other ethnic origins. He also notes that so far, all the subjects come from industrial nations, and thus eat similar foods. “This is a shortcoming,” he said. “We don’t have remote villages.”

The discovery of enterotypes follows on years of work mapping the diversity of microbes in the human body — the human microbiome, as it is known. The difficulty of the task has been staggering. Each person shelters about 100 trillion microbes.

(For comparison, the human body is made up of only around 10 trillion cells.) But scientists cannot rear a vast majority of these bacteria in their labs to identify them and learn their characteristics.

gut microbes influence behavior

TheScientist | Gut microbes acquired early in life can impact brain development in mice and subsequent behavior, such as decreasing physical activity and increasing anxiety, according to a study published this week in the Proceedings of the National Academy of Sciences.

"This paper opens the door to new studies in at least two directions," Yale University microbiologist Andrew Goodman, who was not involved in the research, told The Scientist in an email. "First, determining how differences between complete host-associated microbial communities lead to differences in behavior, and second, exploring the contributions of microbes during specific developmental periods in the host."

Gut microbiota often colonize their hosts early in life, either during pregnancy or following birth, and play an integral role in the health of developing organisms. Previous research has shown that the bacteria affect the development of liver function, the protection epithelial cells afford underlying digestive tissue, gut regulation and the growth of new capillary blood vessels. But this is the first time gut flora have been linked to brain development and behavior.

Harmful microbial infections, on the other hand, have been linked to neurodevelopmental disorders, including autism and schizophrenia. And rodents infected by microbial pathogens before and after birth demonstrated behavioral abnormalities, such as anxiety-like behavior and impaired cognitive function, leading Rochellys Diaz Heijtz, a neurobiologist at the Karolinska Institute in Sweden, and her colleagues to wonder if the gut's normal microbial residents may similarly influence brain development.

The researchers tested exploratory activity in germ-free mice and mice with normal gut microbiota by tracking their movements across open space. They also tested anxiety of the two groups in two classic rodent behavioral tests -- the light-dark box and the elevated maze. Spending more time in lit areas and along unwalled, elevated maze portions equated to less anxiety.

Germ-free mice appeared to be more exploratory than mice with normal microbiota, venturing farther and to more areas of the space provided. Germ-free mice also spent more time in the light and engaged in riskier behavior in the maze, indicating they suffered from less anxiety than their microbe-filled counterparts.

The team then infected germ-free mice with normal gut microbiota when they were born to test whether the gut flora could alter the mice's activity and anxiety levels. Sure enough, the newly infected mice spent less time exploring and engaging in risky behavior, like the normal mice in the initial experiments. The results further supported the argument that the microorganisms can affect brain and behavior when introduced early enough in development.

"These microorganisms communicate in a systemic fashion to the developmental programming of a new individual and can influence fundamental aspects of behavior," said Diaz Heijtz. "We should start to consider the possibility that the microbiome and/or its composition may contribute to psychiatric problems."