NIH Human Microbiome Project Researchers Publish First Genomic Collection of Human Microbes

August 26th, 2010

The Human Microbiome Project (HMP) today published an analysis of 178 genomes from microbes that live in or on the human body. The researchers discovered novel genes and proteins that serve functions in human health and disease, adding a new level of understanding to what is known about the complexity and diversity of these organisms.

The human microbiome consists of all the microorganisms that reside in or on the human body. Outnumbering cells in the human body by 10 to 1, some of the microorganisms cause illnesses, but many are necessary for good health. Currently, researchers can grow only some of the bacteria, fungi and viruses in a laboratory setting. However, new genomic techniques can identify minute amounts of microbial DNA in an individual and determine its identity by comparing the genetic signature to known sequences in the project’s data base. The paper is published in the May 21 issue of the journal Science.

“This initial work lays the foundation for this ambitious project and is critical for understanding the role that the microbiome plays in human health and disease,” said National Institutes of Health Director Francis S. Collins, M.D., Ph.D. “We are only at the very beginning of a fascinating voyage that will transform how we diagnose, treat and ultimately, prevent many health conditions.”

Launched in 2008 as part of the NIH Common Fund’s Roadmap for Medical Research, the HMP is a $157 million, five-year effort that will implement a series of increasingly complicated studies that reveal the interactive role of the microbiome in human health.

The 178 microbial genomes in this report launch the HMP reference collection that eventually will total approximately 900 microbial genomes of bacteria, viruses and fungi. These data will then be used by HMP researchers to characterize the microbial communities found in samples taken from healthy human volunteers and, later, those with specific illnesses. Samples are currently being collected for HMP from five areas of the body: the digestive tract, the mouth, the skin, the nose and the vagina.

“Although this is only the first step in making HMP medically useful, we already have learned surprising things about the diversity and complexity of the microorganisms that live in and on our body,” said Jane Peterson, Ph.D., associate director of the NHGRI Division of Extramural Researcher and a leader of the HMP effort. “The next stages of this coordinated study will begin to associate the presence or absence of specific micro-organisms with various states of health and illness.”

Researchers also conducted a preliminary survey to gain insights into the function of some of the newly identified genes and proteins unique to individual microbial strains. For instance, researchers found previously unknown proteins produced by bacteria that live in the stomach that may cause gastric ulceration, a hole in the stomach lining. In addition, they found a small number of newly identified novel proteins associated with how sugars and amino acids are metabolized.

Researchers also evaluated the microbial diversity present in the HMP reference collection. For example, they found 29,693 previously undiscovered, unique proteins in the reference collection

Human gene catalog shows it’s mostly a mystery

August 19th, 2010

They live in us and on us, helping digest food and keeping acne at bay, and researchers said on Thursday that most of these germs are turning out to be new to science.

The first look at 178 different microbes that live in or on the human body shows that more than 90 percent of their genetic sequences were unknown and raise questions about how scientists classify species among micro-organisms.

“Most people don’t even realize how much microbial diversity we have on and in us,” said Karen Nelson of the J. Craig Venter Institute in Rockville, Maryland, who leads the ongoing study.

“We are dependent on them for digestion of plant material and some vitamins,” she added in a telephone interview.

Yet scientists know very little about the many hundreds of different types of bacteria, viruses and yeast that inhabit the skin, mouth, scalp and most of all, the gut.

“The oceans and the soils have gotten more attention than the human body,” Nelson said.

Researchers at the Baylor College of Medicine in Houston; the Broad Institute in Cambridge, Massachusetts; Washington University in St. Louis and the Venter Institute are working on the $157 million, five-year Human Microbiome Project to survey all the microbes important to human health.

FIGHTING DISEASE

There are hints that healthy colonies of microbes not only process vitamins, but maintain pH balance on the skin, prevent tooth decay, protect against diarrheal infections and defend against sexually transmitted infections.

The researchers recruited 300 healthy volunteers who are allowing themselves to be swabbed and examined. “At least 15 additional projects will focus on disease conditions,” Nelson said.

Reporting on Thursday in the journal Science, Nelson and colleagues described 500,000 new genetic sequences, all from bacteria so far. “There is a lot of diversity. We don’t really know what this means,” she said.

They found more than 29,000 new proteins, which are the compounds made by cells based on their genetic sequences. This suggests these microbes are up to a great deal of previously undocumented activity.

“This initial work lays the foundation for this ambitious project and is critical for understanding the role that the microbiome plays in human health and disease,” said National Institutes of Health director Dr. Francis Collins.

“We are only at the very beginning of a fascinating voyage that will transform how we diagnose, treat and ultimately, prevent many health conditions.”

One they examined, a bacteria called Lactobacillus reuteri, seems to have a distinct genetic sequence for each species whose gut it inhabits — rats, pigs and people. Nelson said there are also indications that individual people host their own unique species of germs.

L. reuteri, found in breast milk, may protect against rotavirus infections, other researchers have found,

In 2006 Steven Gill of the State University of New York in Buffalo estimated that 90 percent of the cells on the human body are actually bacteria.

More Steps a Day Lead to Better Health

August 12th, 2010

Walk a little, and your body will thank you. Walk a lot, and it will really thank you.

That’s the message of a new study that links taking more steps in a day to a lower risk of an extremely common condition known as metabolic syndrome, which can lead to heart disease and diabetes.

The research only shows a connection between more walking and better health — it doesn’t prove that simply walking more will make you healthier. Still, the findings suggest that “you don’t have to be out there running marathons,” said study co-author Peter T. Katzmarzyk, a professor at Pennington Biomedical Research Center in Baton Rouge, La.

Instead, “you just have to incorporate physical activity such as walking into your lifestyle,” he said.

The study, published in the May issue of the American Journal of Preventive Medicine, examined the effects of exercise on metabolic syndrome, which is estimated to affect more than a third of adults in the United States.

People with metabolic syndrome have at least some of the risk factors for heart disease and diabetes — excess weight in the abdomen, elevated blood pressure, low levels of good cholesterol, high triglyceride (blood fat) levels, insulin resistance or elevated blood glucose levels.

The condition serves as a sort of early warning system, Katzmarzyk said. “If you have two, three or four risk factors, you may have a much higher risk of developing full-blown cardiovascular disease than someone who doesn’t,” he said.

Many people with excess weight have metabolic syndrome, but people of normal weight can develop it too, he said.

The study authors examined a 2005-2006 study that tracked 1446 adults (with an average age of 47.5) as they went about their days. The participants wore high-quality pedometers (known as accelerometers) that allowed researchers to accurately count the number of steps they took each day and sort them into three groups: “sedentary” (those who took fewer than 5000 steps a day), “low-to-somewhat-active” (5000 to 9999 steps a day), and “active-to-highly active” (10,000 or more steps a day).

After adjusting their statistics so they wouldnt be thrown off by factors like gender and age, the researchers found that almost 56 percent of those who took the least steps had metabolic syndrome, but just 13 percent of those who took the most steps had it. Overall, about a third had metabolic syndrome.

But even adults who were only somewhat active had a better chance of avoiding the syndrome than those who walked the least. Compared to the sedentary group, people in the “low-to-somewhat-active” group had 40 percent lower odds of developing the condition. People in the “active-to-highly active” had a full 72 percent lower odds of developing it.

In addition, each additional 1,000 steps was associated with an 8-13 percent decrease in the odds of a large waist, in a low level of “good” HDL cholesterol, and in high levels of triglycerides.

Those who walked the most were least likely to have risk factors, Katzmarzyk said.

“There was a trend all the way,” he said. “It’s not that you reach some magical number. Something is better than nothing, and something more than that is even better.”

Since the study didn’t prove a cause-and-effect relationship between walking and lowered odds of metabolic syndrome, other factors could be at play, Katzmarzyk said. For example, people who have metabolic syndrome may be less active because of it.

David R. Bassett Jr., a professor who studies exercise at the University of Tennessee, said the new study is significant because it’s more rigorous than previous research examining the connection between steps taken and metabolic syndrome.

“The amount of walking people do is vitally important for their health,” Bassett said. “The authors measured the total volume of walking performed, not just walking done in bouts of 10 minutes or more, and not just brisk walking. Plain, old walking is good for your health.”

SOURCES: Peter T. Katzmarzyk, Ph.D., professor, Pennington Biomedical Research Center, Baton Rouge, La.; David R. Bassett Jr., Ph.D., professor, Department of Exercise, Sport and Leisure Studies, University of Tennessee, Knoxville.

Older patients can skip breast radiation: study

August 5th, 2010

Older women with early stage breast cancer can safely skip radiation therapy and go straight to taking pills that help keep tumors from coming back, researchers reported on Thursday.

They said the finding, to be presented next month to a meeting of the American Society of Clinical Oncology, may save many women and their doctors a lot of trouble, not to mention the costs of radiation.

“This study confirms that for older women with early stage breast cancer, lumpectomy without radiation is a viable alternative, and tamoxifen may replace the need for radiation,” said Dr. Kevin Hughes of Massachusetts General Hospital in Boston, who led the study.

Hughes and colleagues now have 12 years of data on 636 women aged 70 or older who had stage I breast cancer, the easy-to-cure type that has not spread and that is so-called estrogen receptor-positive.

The women had the tumors removed in an operation called a lumpectomy. Half got radiation treatment and then took five years of tamoxifen, a pill that has been shown to cut in half the risk that breast cancer will return.

The other half went straight to tamoxifen.

Twelve years later, 12 women who got radiation had died from their breast cancer, compared to eight who got tamoxifen only, Hughes told reporters in a telephone briefing. Many of the women died, but more than 95 percent died from something other than breast cancer.

“We did find that radiation did have some benefits in terms of in-breast recurrences but those benefits are relatively small,” Hughes said.

He said 26 women who did not have radiation got new tumors in the same breast, compared to six women who had radiation. Those women could have the new tumors removed and then have radiation later.

ASCO president Dr. Douglas Blayney said the work showed that publicly funded, academic research can help patients in ways that research done by the pharmaceutical industry and device makers would not. “This is the kind of study that would not be done … if we relied on industry,” Blayney said.

“I think that many women and their physicians currently don’t do radiation. This gives us comfort in the fact that this is a reasonable course of action,” Blayney said.

Study Questions Use of Heart Device Implants in the Very Old

July 27th, 2010

A new study questions the widespread use of implantable cardiac devices in the very old, who are more likely to die in the hospital after receiving the devices.

Patients aged 80 and older receive more than one-fifth of implantable defibrillators and pacemakers, even though most clinical trials of the devices haven’t included patients in this age group, the study authors noted.

“Implantable cardiac devices have been increasingly used in primary prevention of sudden cardiac death among patients with systolic heart failure, largely on the basis of favorable results from large multicenter clinical trials,” wrote Jason P. Swindle, then of the Saint Louis University School of Medicine, and colleagues. “However, it has become increasingly apparent that certain patient subgroups may not benefit from device implantation.”

Implanting cardiac defibrillators in patients with kidney failure and in those with advanced heart failure symptoms, for example, “has not been associated with a survival benefit,” he explained.

In this study, the researchers analyzed data from 26,887 adults, median age 70, with heart failure who underwent defibrillator implantation or cardiac resynchronization therapy in 2004 or 2005. Patients aged 80 and older accounted for 17.5 percent of the procedures, including 992 patients older than 85 and 309 patients aged 89 or older.

In-hospital death rates were 0.7 percent among patients younger than 80, but climbed to 1.2 percent among those aged 80 to 85 and 2.2 percent among those older than 85.

The researchers found that the older patients were less likely to have a concurrent cardiac procedure or a high risk of dying from a co-existing condition. For this reason, “these patients may be, in fact, somewhat more carefully selected than the younger cohort. However, older patients had slightly more complications related to the device procedure,” the researchers wrote.

“Given trends in the demographics of heart failure and the costs of device therapy, additional studies are required to clarify the appropriateness of device implantation in older patients with heart failure, as well as the merits of less invasive options,” they concluded.

The study is published in the issue of the journal Archives of Internal Medicine.

Targeting the Blood-Brain Barrier May Delay Progression of Alzheimer’s Disease

July 20th, 2010

Researchers may be one step closer to slowing the onset and progression of Alzheimer’s disease. An animal study supported by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, shows that by targeting the blood-brain barrier, researchers are able to slow the accumulation of a protein associated with the progression of the illness. The blood-brain barrier separates the brain from circulating blood, and it protects the brain by removing toxic metabolites and proteins formed in the brain and preventing entry of toxic chemicals from the blood.

“This study may provide the experimental basis for new strategies that can be used to treat Alzheimer

Teen Drinking May Boost Breast Problems Later

July 13th, 2010

Frequent alcohol consumption by teenage girls may increase the chances that they will develop non-cancerous breast disease in their 20s and possibly breast cancer later in life.

Research published online April 12 in the journal Pediatrics found that girls who drank the most alcohol during their teen years — daily or nearly every day — were five times more likely to develop benign breast disease as young adults than were their peers who never drank or drank less than once a week.

Benign breast disease (BBD) includes a number of nonmalignant conditions. Fibroadenoma, a noncancerous tumor, is the most common in those aged 30 and younger. Study co-author Catherine Berkey, a biostatistician at Harvard Medical School in Boston, said that benign breast disease is known to boost the risk for breast cancer.

So does that mean that teens who drink alcohol are increasing their breast cancer risk early in life?

“Our study may suggest that teen drinking increases the risk for breast cancer, whether in all females or in those who go on to develop BBD, but longer-term follow-up is certainly required” to confirm it, she said.

A unique aspect of Berkey’s study was that the girls assessed their drinking habits while they were teenagers. Other studies have based their conclusions on adult women’s recalling their teenage drinking many years later.

“Our new study is the first in which alcohol data were collected during adolescence, with continued follow-up in the females as they develop disease,” she said.

The study involved 6,899 women who had become participants in the “Growing Up Today Study” when they were 9 to 15 years old. Information on alcoholic beverage consumption was collected in a follow-up survey when the participants were 16 to 23 years old, and a survey done when they were 18 to 27 years old included questions on breast disease.

In all, 147 participants reported having benign breast disease, with 67 cases having been confirmed by biopsy.

When Berkey and her colleagues looked at the diagnoses of benign breast disease and drinking, they found that risk for benign breast disease rose along with the frequency of alcohol consumption: from a 1.5 increased risk for drinking one or two days per week, to a three times greater risk for those drinking three to five days per week, and to a 5.5 times greater risk for drinking six or seven days per week, when compared with those who never drank or who drank less than once per week.

Even once-a-week drinkers may not be absolutely safe, Berkey noted. “I suspect there may be some small additional BBD risk for even small amounts of alcohol consumed during adolescence,” she said.

Teen years are a critical time for potential cancer-producing exposures, she said, because the mammary glands are undergoing rapid growth during that period.

Berkey said she suspects the link is due to alcohol increasing total estrogen levels, raising the likelihood of benign breast disease.

“For me, this is not a surprise,” said Dr. Patricia Ganz, director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. Regular alcohol consumption is known to increase a woman’s risk for both breast cancer and benign breast disease, she said, and “certain forms of BBD increase the risk of breast cancer.”

And though she described the new study as excellent, she cautioned that the sample size was relatively small.

“I wouldn’t scare [teens] and say, ‘You are going to get breast cancer if you drink,’” Ganz said. But, on the other hand, she added: “The public health message is, these young girls shouldn’t be drinking anyway.”

SOURCE: Catherine S. Berkey, Sc.D., biostatistician, Harvard Medical School, Boston; Patricia Ganz, M.D., director, cancer prevention and control research, Jonsson Comprehensive Cancer Center, University of California, Los Angeles;

Shyness May Be Rooted in Brain Processing

July 6th, 2010

Because their brains process the world around them in a different way, introverted or shy people respond differently to physical and emotional stimuli than other people, according to a new study.

About 20 percent of people are “highly sensitive,” an inborn trait that can be seen in children who are reserved, need little disciplining, cry easily, ask unusual questions or have especially deep thoughts, explained Elaine and Arthur Aron and colleagues from Stony Brook University in New York and in China.

Adults who are highly sensitive tend to take longer to make decisions, are more conscientious, spend more time alone to reflect and are more easily bored by small talk, the study authors noted.

The researchers used functional MRI to scan the brains of sensitive and non-sensitive people as they tried to identify small changes in photographs. The changes that the study participants tried to identify were either obvious or subtle.

Compared to non-sensitive people, the sensitive participants looked at the photos that had the subtle changes for a longer time and had much greater activation in brain areas involved in associating visual input with other input to the brain, and with visual attention. These areas aren’t used simply for vision, but for a deeper processing of input.

The findings were recently published online in the journal Social Cognitive and Affective Neuroscience.

Brain scans show signs of early Alzheimer’s: study

June 24th, 2010

People with a family history of Alzheimer’s disease often have clumps of a toxic protein in their brains even though they are perfectly healthy, researchers said on Monday.

They said the findings could lead to new ways to identify people most likely to develop Alzheimer’s disease, when there is still time to do something about it.

“The hope is to one day be able to diagnose very clearly the Alzheimer’s disease process before any symptoms occur, when the brain is still healthy. Then the treatments would have the best chance of success,” said Lisa Moscone of New York University Langone Medical Center, whose study appears in the Proceedings of the National Academy of Sciences.

The team wants to continue to follow the people in the study to see whether they develop dementia, and they want to replicate the findings in a much larger study.

Several teams have been working on better ways to detect early-stage Alzheimer’s disease in hopes of developing drugs that can fight it before it causes too much damage.

Current treatments cannot reverse the course of Alzheimer’s, a mind-robbing form of dementia that affects more than 26 million people globally.

Moscone’s team used an imaging technique called positron emission tomography or PET with a fluorescent dye called Pittsburgh Compound B that lights up clumps of a protein called beta amyloid that are a hallmark of Alzheimer’s disease.

The team imaged the brains of 42 people with an average age of 65, all with healthy brain function. Of these, 14 people had mothers who had Alzheimer’s; 14 had fathers with the disease; and 14 had parents with healthy brain function.

Brain scans of all 42 showed that those whose parents — either fathers or mothers — had Alzheimer’s were more likely to have amyloid plaques in their brains.

This was especially true of people whose mothers had Alzheimer’s.

“They have pretty much 20 percent more amyloid beta deposits in their brains. In other words, they had an almost four times greater risk for amyloid beta pathology,” Moscone said in a telephone interview.

The finding confirms other studies that suggest having a mother with Alzheimer’s may be a greater risk factor.

“It looks like if you have maternal history of Alzheimer’s disease, the risk of amyloid beta plaque and a reduction in brain activity is much greater as compared to having a father affected,” Moscone said.

After advanced age, a family history of Alzheimer’s is the single biggest risk factor for developing the disease.

Not everyone who has beta amyloid plaques in their brain develops Alzheimer’s disease, but Moscone said having the plaques does increase the risk.

(Editing by Eric Walsh)

Boosting Vitamin D Can Do a Heart Good

June 17th, 2010

New research suggests that extra vitamin D could make a major difference in heart disease risk among people who have low levels of the nutrient.

Researchers from the Intermountain Medical Center Heart Institute in Murray, Utah, report in two new studies that vitamin D supplementation may reduce the risk of other chronic diseases, too.

“Vitamin D replacement therapy has long been associated with reducing the risk of fractures and diseases of the bone,” study author Dr. J. Brent Muhlestein, director of cardiovascular research, said in a center news release. “But our findings show that vitamin D could have far greater implications in the treatment and reduction of cardiovascular disease and other chronic conditions than we previously thought.”

The researchers found that patients who boosted their vitamin D levels to 43 nanograms per milliliter of blood or higher reduced their rates of diabetes, heart attack, heart failure, high blood pressure and heart disease. They were also less likely to die during the study period.

According to the researchers, a level of 30 nanograms per milliliter of vitamin D is considered normal.

“Although randomized trials would be useful and are coming, I feel there is enough information here for me to start treatment based on these findings,” Muhlestein said, adding that increasing vitamin D intake by 1,000 to 5,000 international units a day may be a good idea in some cases.

The findings are scheduled to be presented Monday at the American College of Cardiology’s annual meeting in Atlanta.