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Thursday, 06/14/2012 5:08:12 AM

Thursday, June 14, 2012 5:08:12 AM

Post# of 482070
In Good Health? Thank Your 100 Trillion Bacteria

By GINA KOLATA
Published: June 13, 2012

For years, bacteria have had a bad name. They are the cause of infections, of diseases. They are something to be scrubbed away, things to be avoided.

But now researchers have taken a detailed look at another set of bacteria that may play even bigger roles in health and disease: the 100 trillion good bacteria that live in or on the human body.

No one really knew much about them. They are essential for human life, needed to digest food, to synthesize certain vitamins, to form a barricade against disease-causing bacteria. But what do they look like in healthy people, and how much do they vary from person to person?

In a new five-year federal endeavor, the Human Microbiome Project [ http://commonfund.nih.gov/hmp/ ], which has been compared to the Human Genome Project, 200 scientists at 80 institutions sequenced the genetic material of bacteria taken from nearly 250 healthy people [ http://www.nature.com/nature/journal/v486/n7402/full/nature11209.html ].

They discovered more strains than they had ever imagined — as many as a thousand bacterial strains on each person. And each person’s collection of microbes, the microbiome, was different from the next person’s [ http://www.nature.com/nature/journal/v486/n7402/full/nature11234.html ]. To the scientists’ surprise, they also found genetic signatures of disease-causing bacteria lurking in everyone’s microbiome. But instead of making people ill, or even infectious, these disease-causing microbes simply live peacefully among their neighbors.

The results, published on Wednesday in Nature and three PLoS journals, are expected to change the research landscape.

The work is “fantastic,” said Bonnie Bassler, a Princeton University microbiologist who was not involved with the project. “These papers represent significant steps in our understanding of bacteria in human health.”

Until recently, Dr. Bassler added, the bacteria in the microbiome were thought to be just “passive riders.” They were barely studied, microbiologists explained, because it was hard to know much about them. They are so adapted to living on body surfaces and in body cavities, surrounded by other bacteria, that many could not be cultured and grown in the lab. Even if they did survive in the lab, they often behaved differently in this alien environment. It was only with the advent of relatively cheap and fast gene sequencing methods that investigators were able to ask what bacteria were present.

Examinations of DNA sequences served as the equivalent of an old-time microscope, said Curtis Huttenhower of the Harvard School of Public Health, an investigator for the microbiome project. They allowed investigators to see — through their unique DNA sequences — footprints of otherwise elusive bacteria.

The work also helps establish criteria for a healthy microbiome, which can help in studies of how antibiotics perturb a person’s microbiome and how long it takes the microbiome to recover.

In recent years, as investigators began to probe the microbiome in small studies, they began to appreciate its importance. Not only do the bacteria help keep people healthy, but they also are thought to help explain why individuals react differently to various drugs and why some are susceptible to certain infectious diseases while others are impervious. When they go awry they are thought to contribute to chronic diseases and conditions like irritable bowel syndrome, asthma, even, possibly, obesity.

Humans, said Dr. David Relman, a Stanford microbiologist, are like coral, “an assemblage of life-forms living together.”

Dr. Barnett Kramer, director of the division of cancer prevention at the National Cancer Institute, who was not involved with the research project, had another image. Humans, he said, in some sense are made mostly of microbes. From the standpoint of our microbiome, he added, “we may just serve as packaging.”

The microbiome starts to grow at birth, said Lita Proctor, program director for the Human Microbiome Project. As babies pass through the birth canal, they pick up bacteria from the mother’s vaginal microbiome.

“Babies are microbe magnets,” Dr. Proctor said. Over the next two to three years, the babies’ microbiomes mature and grow while their immune systems develop in concert, learning not to attack the bacteria, recognizing them as friendly.

Babies born by Caesarean section, Dr. Proctor added, start out with different microbiomes, but it is not yet known whether their microbiomes remain different after they mature. In adults, the body carries two to five pounds of bacteria, even though these cells are minuscule — one-tenth to one-hundredth the size of a human cell. The gut, in particular, is stuffed with them.

“The gut is not jam-packed with food; it is jam-packed with microbes,” Dr. Proctor said. “Half of your stool is not leftover food. It is microbial biomass.” But bacteria multiply so quickly that they replenish their numbers as fast as they are excreted.

The bacteria also help the immune system, Dr. Huttenhower said. The best example is in the vagina, where they secrete chemicals that can kill other bacteria and make the environment slightly acidic, which is unappealing to other microbes.

Including the microbiome as part of an individual is, some researchers said, a new way to look at human beings.

It was a daunting task, though, to investigate the normal human microbiome. Previous studies of human microbiomes had been small and had looked mostly at fecal bacteria or bacteria in saliva in healthy people, or had examined things like fecal bacteria in individuals with certain diseases, like inflammatory bowel disease, in which bacteria are thought to play a role.

But, said Barbara B. Methé, an investigator for the microbiome study and a microbiologist at the J. Craig Venter Institute, it was hard to know what to make of those studies.

“We were stepping back and saying, ‘We don’t really have a population study. What does a normal microbiome look like?’ ” she said.

The first problem was finding completely healthy people for the study. The investigators recruited 600 subjects, ages 18 to 40, poking and prodding them. They brought in dentists to probe their gums, looking for gum disease, and pick at their teeth, looking for cavities. They brought in gynecologists to examine the women to see if they had yeast infections. They examined skin and tonsils and nasal cavities. They made sure the subjects were not too fat and not too thin. Even though those who volunteered thought they filled the bill, half were rejected because they were not completely healthy. And 80 percent of those who were eventually accepted first had to have gum disease or cavities treated by a dentist.

When they had their subjects — 242 men and women deemed free of disease in the nose, skin, mouth, gastrointestinal tract and, for the women, vagina — the investigators collected stool samples and saliva, and scraped the subjects’ gums and teeth and nostrils and their palates and tonsils and throats. They took samples from the crook of the elbow and the folds of the ear. In all, women were sampled in 18 places, including three sites in the vagina, and men in 15. The investigators resampled subjects three times during the course of the study to see if the bacterial composition of their bodies was stable, generating 11,174 samples.

To catalog the body’s bacteria, researchers searched for DNA with a specific gene, 16S rRNA, that is a marker for bacteria and whose slight sequence variations can reveal different bacterial species. They sequenced the bacterial DNA to find the unique genes in the microbiome. They ended up with a deluge of data, much too much to study with any one computer, Dr. Huttenhower said, creating “a huge computational challenge.”

The next step, he said, is to better understand how the microbiome affects health and disease and to try to improve health by deliberately altering the microbiome.

But, Dr. Relman said, “we are scratching at the surface now.”

It is, he said, “humbling.”

© 2012 The New York Times Company

http://www.nytimes.com/2012/06/14/health/human-microbiome-project-decodes-our-100-trillion-good-bacteria.html [ http://www.nytimes.com/2012/06/14/health/human-microbiome-project-decodes-our-100-trillion-good-bacteria.html?pagewanted=all ]


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The Human Microbiome Project Collection



The healthy adult body hosts ten times as many microbial cells as human cells, including bacteria, archaea, viruses, and eukaryotic microbes resident on nearly every body surface. The metagenome carried collectively by these microbial communities dwarfs the human genome in size, and their influences on normal development, diet and obesity, immunity, and disease are under active research.

Funded by the National Institutes of Health Common Fund, the Human Microbiome Project (HMP) was established to provide a comprehensive baseline of the microbial diversity at 18 different human body sites. This includes reference genomes of host-associated microbial isolates, 16S rRNA marker gene sequencing for thousands of healthy microbiomes, 3.5Tb of metagenomic sequences, assemblies, and metabolic reconstructions, and a catalogue of over 5M microbial genes. These data join resources generated by computational tool development for analysis of the microbiome, research on the ethical, legal, and social implications of the microbiota, technology development for investigating these microbial communities, and a range of disease-focused microbiome demonstration projects. All resources generated by the Human Microbiome Project are publicly available at: http://hmpdacc.org.

The Human Microbiome Project Collection encompasses publications from consortium members generating, leveraging, and exploring these resources. Articles are presented in order of publication date and new articles will be added to the Collection as they are published. For more information on the Human Microbiome Project, please contact HMPinformation@mail.nih.gov.

Research Articles

Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome
Sahar Abubucker, Nicola Segata, Johannes Goll, Alyxandria M. Schubert, Jacques Izard, Brandi L. Cantarel, Beltran Rodriguez-Mueller, Jeremy Zucker, Mathangi Thiagarajan, Bernard Henrissat, Owen White, Scott T. Kelley, Barbara Methé, Patrick D. Schloss, Dirk Gevers, Makedonka Mitreva, Curtis Huttenhower
PLoS Computational Biology:
Published 13 Jun 2012 | info:doi/10.1371/journal.pcbi.1002358
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002358

Diverse CRISPRs Evolving in Human Microbiomes
Mina Rho, Yu-Wei Wu, Haixu Tang, Thomas G. Doak, Yuzhen Ye
PLoS Genetics:
Published 13 Jun 2012 | info:doi/10.1371/journal.pgen.1002441
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002441

Inflammatory Bowel Diseases Phenotype, C. difficile and NOD2 Genotype Are Associated with Shifts in Human Ileum Associated Microbial Composition
Ellen Li, Christina M. Hamm, Ajay S. Gulati, R. Balfour Sartor, Hongyan Chen, Xiao Wu, Tianyi Zhang, F. James Rohlf, Wei Zhu, Chi Gu, Charles E. Robertson, Norman R. Pace, Edgar C. Boedeker, Noam Harpaz, Jeffrey Yuan, George M. Weinstock, Erica Sodergren, Daniel N. Frank
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0026284
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026284

Sequence Analysis of the Human Virome in Febrile and Afebrile Children
Kristine M. Wylie, Kathie A. Mihindukulasuriya, Erica Sodergren, George M. Weinstock, Gregory A. Storch
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0027735
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027735

Complex Carbohydrate Utilization by the Healthy Human Microbiome
Brandi L. Cantarel, Vincent Lombard, Bernard Henrissat
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0028742
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028742

A Case Study for Large-Scale Human Microbiome Analysis Using JCVI’s Metagenomics Reports (METAREP)
Johannes Goll, Mathangi Thiagarajan, Sahar Abubucker, Curtis Huttenhower, Shibu Yooseph, Barbara A. Methé
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0029044
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029044

Host Genes Related to Paneth Cells and Xenobiotic Metabolism Are Associated with Shifts in Human Ileum-Associated Microbial Composition
Tianyi Zhang, Robert A. DeSimone, Xiangmin Jiao, F. James Rohlf, Wei Zhu, Qing Qing Gong, Steven R. Hunt, Themistocles Dassopoulos, Rodney D. Newberry, Erica Sodergren, George Weinstock, Charles E. Robertson, Daniel N. Frank, Ellen Li
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0030044
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030044

Analyses of the Microbial Diversity across the Human Microbiome
Kelvin Li, Monika Bihan, Shibu Yooseph, Barbara A. Methé
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0032118
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032118

A Core Human Microbiome as Viewed through 16S rRNA Sequence Clusters
Susan M. Huse, Yuzhen Ye, Yanjiao Zhou, Anthony A. Fodor
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0034242
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0034242

Novel Bacterial Taxa in the Human Microbiome
Kristine M. Wylie, Rebecca M. Truty, Thomas J. Sharpton, Kathie A. Mihindukulasuriya, Yanjiao Zhou, Hongyu Gao, Erica Sodergren, George M. Weinstock, Katherine S. Pollard
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0035294
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035294

Optimizing Read Mapping to Reference Genomes to Determine Composition and Species Prevalence in Microbial Communities
John Martin, Sean Sykes, Sarah Young, Karthik Kota, Ravi Sanka, Nihar Sheth, Joshua Orvis, Erica Sodergren, Zhengyuan Wang, George M. Weinstock, Makedonka Mitreva
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0036427
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036427

A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy
Kjersti Aagaard, Kevin Riehle, Jun Ma, Nicola Segata, Toni-Ann Mistretta, Cristian Coarfa, Sabeen Raza, Sean Rosenbaum, Ignatia Van den Veyver, Aleksandar Milosavljevic, Dirk Gevers, Curtis Huttenhower, Joseph Petrosino, James Versalovic
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0036466
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0036466

Evaluation of 16S rDNA-Based Community Profiling for Human Microbiome Research
Jumpstart Consortium Human Microbiome Project Data Generation Working Group
PLoS ONE:
Published 13 Jun 2012 | info:doi/10.1371/journal.pone.0039315
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0039315

Reducing the Effects of PCR Amplification and Sequencing Artifacts on 16S rRNA-Based Studies
Patrick D. Schloss, Dirk Gevers, Sarah L. Westcott
PLoS ONE:
Published 14 Dec 2011 | info:doi/10.1371/journal.pone.0027310
http://www.ploscollections.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027310

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution License.

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"Eternal vigilance is the price of Liberty."
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