NIH Human Microbiome Project defines normal bacterial makeup of the body.


Genome sequencing creates first reference data for microbes living with healthy adults

Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for human survival. For the first time, a consortium of researchers organized by the National Institutes of Health has mapped the normal microbial makeup of healthy humans, producing numerous insights and even a few surprises.

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.

In a series of coordinated scientific reports published on June 14, 2012, in Nature and several journals in the Public Library of Science (PLoS), some 200 members of the Human Microbiome Project (HMP) Consortium from nearly 80 universities and scientific institutions report on five years of research. HMP has received $153 million since its launch in fiscal year 2007 from the NIH Common Fund, which invests in high-impact, innovative, trans-NIH research. Individual NIH institutes and centers have provided an additional $20 million in co-funding for HMP consortium research.

“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.”

Methods and Results

The human body contains trillions of microorganisms — outnumbering human cells by 10 to 1. Because of their small size, however, microorganisms make up only about 1 to 3 percent of the body’s mass (in a 200-pound adult, that’s 2 to 6 pounds of bacteria), but play a vital role in human health.

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. Using computers, researchers sorted through the 3.5 terabases of genome sequence data to identify specific genetic signals found only in bacteria — the variable genes of bacterial ribosomal RNA called 16S rRNA. Bacterial ribosomal RNA helps form the cellular structures that manufacture protein and can identify the presence of different microbial species.

Focusing on this microbial signature allowed HMP researchers to ignore the human genome sequences and analyze only the bacterial DNA. In addition, metagenomic sequencing, or sequencing all of the DNA in a microbial community, allowed the researchers to study the metabolic capabilities encoded in the genes of these microbial communities.

“Recently developed genome sequencing methods now provide a powerful lens for looking at the human microbiome,” said Eric D. Green, M.D., Ph.D., director of the National Human Genome Research Institute, which managed HMP for NIH. “The astonishing drop in the cost of sequencing DNA has made possible the kind of large survey performed by the Human Microbiome Project.”

Where doctors had previously isolated only a few hundred bacterial species from the body, HMP researchers now calculate that more than 10,000 microbial species occupy the human ecosystem. Moreover, researchers calculate that they have identified between 81 and 99 percent of all microorganismal genera in healthy adults.

“We have defined the boundaries of normal microbial variation in humans,” said James M. Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning and Strategic Initiatives, which includes the NIH Common Fund. “We now have a very good idea of what is normal for a healthy Western population and are beginning to learn how changes in the microbiome correlate with physiology and disease.”

HMP researchers also reported that this plethora of microbes contribute more genes responsible for human survival than humans contribute. Where the human genome carries some 22,000 protein-coding genes, researchers estimate that the human microbiome contributes some 8 million unique protein-coding genes or 360 times more bacterial genes than human genes.

This bacterial genomic contribution is critical for human survival. Genes carried by bacteria in the gastro-intestinal tract, for example, allow humans to digest foods and absorb nutrients that otherwise would be unavailable.

“Humans don’t have all the enzymes we need to digest our own diet,” said Lita Proctor, Ph.D., NHGRI’s HMP program manager. “Microbes in the gut break down many of the proteins, lipids and carbohydrates in our diet into nutrients that we can then absorb. Moreover, the microbes produce beneficial compounds, like vitamins and anti-inflammatories that our genome cannot produce.” Anti-inflammatories are compounds that regulate some of the immune system’s response to disease, such as swelling.

Researchers were surprised to discover that the distribution of microbial metabolic activities matters more than the species of microbes providing them. In the healthy gut, for example, there will always be a population of bacteria needed to help digest fats, but it may not always be the same bacterial species carrying out this job.

“It appears that bacteria can pinch hit for each other,” said Curtis Huttenhower, Ph.D., of Harvard School of Public Health and lead co-author for one of the HMP papers in Nature. “It matters whether the metabolic function is present, not which microbial species provides it.”

Moreover, the components of the human microbiome clearly change over time. When a patient is sick or takes antibiotics, the species that makeup of the microbiome may shift substantially as one bacterial species or another is affected. Eventually, however, the microbiome returns to a state of equilibrium, even if the previous composition of bacterial types does not.

Clinical Applications

As a part of HMP, NIH funded a number of studies to look for associations of the microbiome with diseases and several PLoS papers include medical results. For example, researchers at the Baylor College of Medicine in Houston compared changes in the vaginal microbiome of 24 pregnant women with 60 women who were not pregnant and found that the vaginal microbiome undergoes a dramatic shift in bacterial species in preparation for birth, principally characterized by decreased species diversity. A newborn is a bacterial sponge as it populates its own microbiome after leaving the sterile womb; passage through the birth canal gives the baby its first dose of microbes, so it may not be surprising that the vaginal microbiome evolved to make it a healthy passage.

Researchers at the Washington University School of Medicine in St. Louis examined the nasal microbiome of children with unexplained fevers, a common problem in children under 3 years of age. Nasal samples from the feverish children contained up to five-fold more viral DNA than children without fever, and the viral DNA was from a wider range of species. Previous studies show that viruses have ideal temperature ranges in which to reproduce. Fevers are part of the body’s defense against pathogenic viruses, so rapid tests for viral load may help children avoid inappropriate treatment with antibiotics that do not kill the viruses but may harm the child’s healthy microbiome.

These are among the earliest clinical studies using microbiome data to study its role in specific illnesses. NIH has funded many more medical studies using HMP data and techniques, including the role of the gut microbiome in Crohn’s disease, ulcerative colitis and esophageal cancer; skin microbiome in psoriasis, atopic dermatitis and immunodeficiency; urogenital microbiome in reproductive and sexual history and circumcision; and a number of childhood disorders, including pediatric abdominal pain, intestinal inflammation, and a severe condition in premature infants in which the intestine actually dies.

“Enabling disease-specific studies is the whole point of the Human Microbiome Project,” said Barbara Methé, Ph.D., of the J. Craig Venter Institute, Rockville, MD, and lead co-author of the Nature paper on the framework for current and future human microbiome research. “Now that we understand what the normal human microbiome looks like, we should be able to understand how changes in the microbiome are associated with, or even cause, illnesses.”

The NIH Common Fund also invested in a series of studies to evaluate the ethical, legal and social implications of microbiome research. While the results of these studies are yet to be published, a number of important issues already have been identified, ranging from how products designed to manipulate the microbiome — such as probiotic concoctions that include live microorganism believed to benefit the body — might be regulated, to whether individuals should begin to consider storing their microbiome while healthy.

After NIH launched HMP in December 2007, the International Human Microbiome Consortium formed in 2008 to represent funding organizations, including NIH, and scientists from around the world interested in studying the human microbiome. The consortium has coordinated research to avoid duplication of effort and insured rapid release of molecular and clinical data sets. It also has developed common data quality standards and tools to share research results.

Microbes ‘cheaper, fairer’ for boosting yields than GM.


Speed read

  • Microbes may offer a more equitable choice for smallholder farmers
  • Improvements in technology must continue to get them from the lab to the field
  • Melon yields in Honduras have already benefited from microbes.

Adapting microbes that dramatically increase crop yields while reducing demand for fertilisers and pesticides through selective breeding or genetic engineering could be cheaper and more flexible than genetically modifying plants themselves, says an author of a report.
 
Microbes, such as beneficial bacteria, fungi and viruses, could be produced locally for smallholder 
farmers to significantly improve food security and incomes in developing regions, believes Ann Reid, director of the American Academy of Microbiology and co-author of a report published by the organisation last month (27 August).
 
“Genetic modification of crop plants, which has seen a huge investment, is closed to all but the biggest agricultural companies,” she tells SciDev.Net.
 
“Optimisation of microbes could be done at the level of the local community college and is much more obtainable for a smallholder farmer.”
 
Her comments echo the findings of the report — the product of an expert meeting in 2012 — which underscored the significant impact microbes could have on food production by increasing crops’ absorption of nutrients, resistance to disease and environmental stresses, and even improving flavour.
 

“Optimisation of microbes could be done at the level of the local community college and is much more obtainable for a smallholder farmer.”

Ann Reid, American Academy of Microbiology

As well as to accentuate naturally occurring traits such as the secretion of pest-killing toxins or nitrogen-fixation, the modification of microbes is often needed to allow them to be grown in large numbers out of their natural environment.
 
For example, researchers in Colombia could only produce large quantities of a fungus that improves the nutrient absorption of cassava once they bred a strain of that fungus that was capable of growing on carrot roots.
 
Recent technological developments in rapid DNA sequencing, imaging and computer modelling can help provide further solutions, as well as building a greater understanding of the complex environment that microbes themselves need to flourish, the report says.
 
These advances raise the possibility that, within two decades, microbes could increase food production by a fifth and reduce fertiliser demands by the same proportion, it finds.
 
But to achieve this ambitious goal, the research community must engage in curiosity-driven basic research, develop even cheaper sequencing techniques, and establish a process to move discoveries from the lab to the field, it says.
 
Reid adds that, unlike genetic modification, which requires farmers to regularly buy improved seeds, microbes may be able to stay in the soil indefinitely.
 
But larger universities are still needed to drive more-complex areas of investigation, which inevitably requires funding, she says. “We wanted to get the word out that this could be a big-bang-for-your- buck area for funding agencies.”
 
Matteo Lorito, a professor of plant pathology at the University of Naples, Italy, agrees that sophisticated research centres must be involved in identifying and selecting suitable microbes and techniques.
 
But once this groundwork has been done, growing microbes will require as little as a fermenting tank, he says.
 
The impact of this approach is already being seen in areas such as Honduras, where melon yields have been improved by 15 per cent by applying a fungus that boosts the plants’ defence mechanisms.
 
Other crops such as maize, tomatoes and wheat could see rises in production of more than 50 per cent from such techniques, he believes.
 
But Ken Giller, professor of plant production systems at the Netherland’s Wageningen University, says that much more work needs to be done, particularly on how to get the microbes into the soil, before farmers will benefit, he says.
 
“Molecular biology has been incredibly important in understanding biology in general, which has helped when thinking about solutions [for food production],” he tells SciDev.Net.
 
“But in terms of the manipulation of these processes to make an impact in the field, we have yet to make any great inroads

Gut Microbes Can Split a Species.


Here’s how to create a new species. Put animals—say finches—from the same species on separate islands and let them do their thing for many, many generations. Over time, each group will adapt to its new environment, and the genomes of the two populations will become so different that if you reintroduce the animals to the same habitat, they can no longer breed successfully. Voilà, one species has become two. But a new study suggests that DNA isn’t the only thing that separates species: Some populations diverge because of the microbes in their guts.

 

The paper is “important and potentially groundbreaking,” says John Werren, a biologist at the University of Rochester in New York. “Scientists have studied speciation … for many years, and this opens up a whole new aspect to it.”

The new work involves three different species of parasitic jewel wasps, tiny insects that drill into the pupas of flies and lay their eggs, letting the offspring feed on the host. Two of the species, Nasonia giraulti and N. longicornis, are closely related, whereas the third species, N. vitripennis, diverged from the other two about 1 million years ago. When N. giraultiand N. longicornis mate in the lab, most of their offspring survive, but when either mates with N. vitripennis, almost all male larvae in the second generation die.

Seth Bordenstein and Robert Brucker, biologists at Vanderbilt University in Nashville, wondered if the reason for this mortality went beyond incompatible DNA. They knew that the gut microbes in N. vitripennis differed from those in the other two species, and they suspected that these microbes could play a role in the offspring deaths. Indeed, when they raised all three species of Nasonia without gut microbes—by rearing them on sterile food—almost all the second generation offspring of matings between N. vitripennis and N. giraulti wasps survived. Andwhen the scientists reintroduced bacteria into the germ-free wasps, most of their second-generation offspring died, the duo report online today in Science.

Werren says that the work introduces a whole new way to look at what sets species apart. Instead of just thinking about genes of the parents not meshing in hybrids, he says, biologists could now think about how the parents’ genes are incompatible with the offspring’s microorganisms. Some parental genes could enable the immune system to keep certain gut bacteria in check, for instance, and without them the gut microbes might sicken the animal and kill it.

Bordenstein goes one step further. The genes of microbes harbored by an organism are just as important for evolution as the genes in its own cells, he says, calling both together a “hologenome.” Werren disagrees. Microbes in the gut interact with the bigger organism, just like other organisms in nature interact, for instance predator and prey, Werren says. “They are not co-evolving as a single unit, so why would we call them a single genome?”

Axel Meyer, an evolutionary biologist at the University of Konstanz in Germany, is skeptical about whether gut microbes have a big effect on speciation. The paper is “exciting,” he says, “but there might be huge biological differences between species in how the microbiome [the community of microbes in an organism] is established.” As a result, he says, it is an open question whether there will be many more examples of gut microbes separating species. Werren thinks there will be. “No pun intended,” he says, “but my gut tells me that this is going to be common.”

Source: sciencemag.org

The Long and Arduous Quest to Find Flowing Water on Mars May Be Over.


mars-in-motion_2

Discoveries of water on Mars are now so common that the subject has become the butt of jokes among planetary scientists: “Congratulations—you’ve discovered water on Mars for the 1,000th time!”

Most of these findings have involved either visual evidence for ancient, long-gone water or evidence for present-day ice, vapor or hydrated minerals. The discovery of actual liquid water on the surface, in the present day, could change the course of Mars exploration. Where there is water on Earth, there is almost always life. Confirming the existence of water on Mars would therefore greatly improve the prospect of finding extraterrestrial life. This is the story of continuing efforts to uncover what role, if any, liquid water plays on Mars today.

In Brief

  • High-resolution orbital imaging over multiple Martian years is revealing all manner of surface changes, some of which may involve liquid water.
    • Surface features known as gullies were once thought to require the presence of water, but recent evidence suggests otherwise.
    • A newly discovered class of features on warm slopes may mark the flow of salty water. These sites could be the best places to look for microbial life on Mars.

Source: http://www.scientificamerican.com

 

 

 

Pregnancy Alters Resident Gut Microbes.


The microbes that reside in your gut are very much a living, and integral, part of you.

Far from being just passive bystanders, the bacteria are impacted by your health, your lifestyle and even your life stages – and they actively change in response to different periods of your life, like pregnancy.

Your Gut Microbes Change During Each Pregnancy Trimester to Support Fetal Growth

The composition of a woman’s gut microbes actually changes during each trimester of pregnancy in ways that support the growth of the fetus. This is largely influenced by the hormonal shifts that occur during pregnancy.

Interestingly, for the first time, research has shown the microbes actually become less diverse and the number of beneficial bacteria decline while disease-related bacteria increase. Under normal circumstances, such changes could lead to weight gain and inflammation, but in pregnancy, they induce metabolic changes that promote energy storage in fat tissue so the fetus can grow.1

The study’s lead author noted:2

“The findings suggest that our bodies have coevolved with the microbiota and may actually be using them as a tool — to help alter the mother’s metabolism to support the growth of the fetus.”

The importance of gut flora continues during and after birth, and may have a profound influence on the baby’s health and development. An article in Science Daily reported on the featured findings of one related study,3 stating:4

“Each individual’s community of gut microbes is unique and profoundly sensitive to environmental conditions, beginning at birth. Indeed, the mode of delivery during the birthing process has been shown to affect an infant’s microbial profile. Communities of vaginal microbes change during pregnancy in preparation for birth, delivering beneficial microbes to the newborn.

At the time of delivery, the vagina is dominated by a pair of bacterial species, Lactobacillus and Prevotella. In contrast, infants delivered by caesarean section typically show microbial communities associated with the skin, including Staphylococcus, Corynebacterium, and Propionibacterium.  While the full implications of these distinctions are still murky, evidence suggests they may affect an infant’s subsequent development and health, particularly in terms of susceptibility to pathogens.”

Interestingly, gut flora is not the only factor influenced by the method of birth. One recent study showed that vaginal birth triggers the expression of mitochondrial uncoupling protein 2 (UCP2) in mice, which is important for improving brain development and function in adulthood. The expression of this protein was impaired in mice born via caesarean section (C-section).5

Mom’s Gut Bacteria Seriously Impacts Baby’s Future Health

Microorganisms in your gastrointestinal tract form a highly intricate, living “fabric” that affects body weight, energy, and nutrition, among other factors.

Not only is each individual’s community of gut microbes unique, but the groundwork for each person’s gut flora is laid from birth. In fact, the mode of delivery during the birthing process has been shown to affect an infant’s microbial profile. This is in part why it’s so important for pregnant women to become mindful of their gut health, as it will affect not just their own health, but also that of their child.

The health implications of this variation in gut bacteria acquired from birth is exactly what Dr. Natasha Campbell-McBride‘s research sheds light upon. Her research shows there’s a profound dynamic interaction between your gut, your brain, and your immune system, starting from birth. She has developed what might be one of the most profoundly important treatment strategies for a wide range of neurological, psychological, and autoimmune disorders—all of which are heavily influenced by your gut health.

I believe her Gut and Psychology Syndrome, and Gut and Physiology Syndrome (GAPS) Nutritional program is vitally important for MOST people, as the majority of people have such poor gut health due to poor diet and toxic exposures, but it’s particularly crucial for pregnant women and young children.

According to Dr. Campbell-McBride, in children with GAPS, the toxicity flowing from their gut throughout their bodies and into their brains continually challenges their nervous system, preventing it from performing its normal function and process sensory information. GAPS may manifest in a wide range of symptoms, fitting the diagnosis of either autism, or attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD) without hyperactivity, dyslexia, dyspraxia, or obsessive-compulsive disorder, just to name a few possibilities… She explained:

What I see in the families of autistic children is that 100 percent of mom’s of autistic children have abnormal gut flora and health problems related to that. But then I look at grandmothers on the mother’s side, and I find that the grandmothers also have abnormal gut flora, but much milder.”

In essence, what we have is a generational build-up of abnormal gut flora, with each generation becoming ever more prone to being further harmed.

What Might be Putting Your Gut Flora at Risk?

If you’ve taken antibiotics or birth control pills, if you eat a lot of processed or sugary foods – even if you were bottle-fed as a baby, all of these can impact the makeup of bacteria and microbes in your gut.

For instance, we now know that breastfed babies develop entirely different gut flora compared to bottle-fed babies. Infant formula never was, and never will be, a healthy replacement to breast milk, for a number of reasons — altered gut flora being one of them.

Dr. Campbell-McBride discovered that a large percentage of the mothers of autistic children were bottle-fed. Then, as they received many courses of antibiotics throughout their childhood, the abnormalities in their gut flora further deepened.

“Ever since antibiotics were prescribed, particularly from the 50s and 60s, they were prescribed for every cough and sneeze. They really over-prescribed antibiotics. And with every course of antibiotics, the abnormalities in the gut flora would get deeper and deeper in these girls. And then, at the age of 15, 16, these ladies were put on a contraceptive pill… [which] have a devastating effect on the gut flora. Nowadays ladies are taking it for quite a few years before they’re ready to start their family.”

So, to recap, bottle-feeding along with over-use of antibiotics and use of the contraceptive pill set the stage for increasingly abnormal gut flora with each passing generation. Then, add to that a diet of processed junk food and excessive consumption of fructose and other sugars and you have a prescription for disaster in terms of gastrointestinal health.

Dr. Campbell-McBride continued:

“Many of these modern factors created a whole plethora of young ladies in our modern world who have quite deeply abnormal gut flora by the time they are ready to have their first child. This is the abnormal gut flora that they are passing through their children.

So these babies acquire abnormal gut flora from the start and while the baby is breastfed the baby is receiving protection because whatever is in the mother’s blood will be in her milk. Women who have abnormal gut flora would have immune factors in their blood, which they have developed against their own gut flora to protect them. These immune factors will be in their milk.

While the baby is breastfed, despite the fact that the baby has acquired abnormal gut flora from the mom, there will be some protection. But as soon as the breastfeeding stops that protection stops as well. That is the time when the abnormalities in the gut flora really flourish and the child starts sliding down into autism or ADHD or ADD or any other learning disability or physical problems such as diabetes type 1, for example, and celiac disease or other autoimmune conditions, or… asthma, eczema and other physical problems. That’s where this epidemic comes from.”

If You’re Pregnant, This is One of the Healthiest Types of Food to Eat

Maintaining optimal gut flora by eating raw food grown in healthy, organic soil and ‘reseeding’ your gut with fermented foods and probiotics (this is essential when you’re taking an antibiotic), may be one of the most important steps you can take to improve your health and your baby’s during pregnancy. If you aren’t eating fermented foods, you most likely need to supplement with a probiotic on a regular basis, especially if you’re eating a lot of processed foods.

If you’re pregnant, however, I strongly recommend adding fermented foods to your diet. You can ferment virtually any food, and nearly every culture has traditionally fermented their foods to prevent spoilage. There are also many fermented beverages and yoghurts.

Fermenting your own foods is a fairly straightforward process. To learn more, please listen to my interview with Caroline Barringer, a Nutritional Therapy Practitioner (NTP) who has been involved with nutrition for about 20 years and is an expert in the preparation of the foods prescribed in Dr. Campbell-McBride’s GAPS Nutritional Program.

What Can You do to Encourage Healthy Gut Flora Once Your Baby is Born?

Breastfeeding was designed by nature to ensure that your child’s gut flora develops properly right from the start, as it is loaded both with beneficial bacteria and nutrient growth factors that will support their continued growth. It also has powerful components that will inhibit the growth of pathogenic bacteria and yeast. So one of the most important foundational elements of building a healthy GI system for your child is to first eat a healthy diet with fermented foods while you’re pregnant, and then breastfeed (whenever possible) for at least one year after your child is born.

Providing abundant beneficial bacteria in the form of breast milk and, later, fermented foods is one of the most powerful ways to restore your baby’s gut flora.

Once your baby is ready to start solid foods, the first fermented food Dr. Campbell-McBride recommends for your infant is raw organic grass-fed yogurt (not commercial yogurt from the grocery store), because it’s well tolerated by most infants and children. It’s best to make your own yogurt at home from raw organic milk, and start with a very tiny amount. Once yogurt is well tolerated by your baby, then start introducing kefir. If you have any problems with cow’s milk, you can always try goat’s milk or substitute vegetables fermented with yogurt culture or kefir culture.

  • ·         Source: Dr. Mercola