Bugs and the Body

Do bacteria contribute to human health, and how?

As organizers and participants gear up for the Fourth International Human Microbiome Congress 2013 in Hangzhou, September 13th–15th, research reports continue to document the critical role of bacteria in human health. At the same time, a wealth of probiotic mythology promising that good gut bacteria can cure everything from Crohn’s disease and obesity to cancer continues to be misleading.
But there is some truth in advertising, if the power of the biome could be harnessed in a rational way. As Martin J. Blaser, M.D., Muriel G. and George W. Singer professor of translational medicine and director of Human Microbiome Program at the New York University School of Medicine, put it in an interview for a New Yorker article, “Germs make us sick. But everyone focuses on the harm. And it’s not that simple, because without most of these organisms we could never survive.”
The almost ten thousand bacterial species we share our bodies with, scientists say, outnumber our own by ten to one, and weigh about three pounds—the same as our brain. This “microbiome” plays such a crucial role in our lives that scientists like Blaser have begun to reconsider “what it means to be human.”

The Human Microbiome Project

In Nature last January, David A. Relman, M.D., and his colleagues commented that “the shared evolutionary fate of humans and their symbiotic bacteria has selected for mutualistic interactions that are essential for human health, and ecological or genetic changes that uncouple this shared fate can result in disease. In this way, looking to ecological and evolutionary principles might provide new strategies for restoring and maintaining human health.”

But while knowledge continues to accumulate detailing how bacteria interact among themselves, with human cells, and how their metabolism affects their human habitats, “there are relatively few circumstances where you can meet a patient who is benefitting from this,” says Dr. Relman, adding that our biome is “a complex and dynamic network.” Dr. Relman is a professor of medicine and of microbiology & immunology at Stanford University, and his research program focuses on the human microbiome.

And an individual’s microbiome is as unique as the DNA in their cells, investigators are discovering. In June 2012, in an article in Nature entitled “Structure, function, and diversity of the healthy human microbiome,” results of studies conducted by the Human Microbiome Project reported, “We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals,” niche meaning the intestinal tract and other body mucosa that microbes habitually inhabit.

The five-year NIH-funded $157 million project sequenced and classified 900 microbes believed to play a role in human health. Goals of the project included development of microbiome taxonomic, metagenomic, and functional data from clinical biospecimens obtained from a cohort(s) of carefully phenotyped subjects with a specific disease or health state, and the combination of the microbiome and host data to produce a community resource.

But Dr. Relman noted with regard to expectations generated around the information produced from the microbiome project, “There’s sensitivity about the expected returns. We need to be grounded about what it is we’ll be able to gain at what point in time. I think the shorter-term gains may be around diagnostics, and novel ways of classifying both health and disease.”

The long-term objective of the initiative is to develop a dataset that the community can utilize to explore whether study of the human microbiome beyond sequenced-based analyses will yield important new insights in understanding human health and disease.

The consortium of scientists have already found the diversity and abundance of each habitat’s (gut, skin, and vagina) signature microbes varied widely even among healthy subjects, with strong niche specialization both within and among individuals.

The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata.

Analysis of the sequences of the first 178 microbes, which was published in the May 21, 2010, issue of Science, “held some surprises” particularly with regard to the extent and complexity of microbial diversity. About 90% of their DNA was previously unknown. The study also identified novel genes and proteins that contribute to human health and disease.

Data emerging from this project, consortium investigators hope, could lead to development of new diagnostic tests because individual biomes are as unique, some scientists say, as an individual’s DNA.

Quantitative Metagenomics

And this data is already enabling new research. Earlier this year, Danish research, citing the obesity epidemic in developed nations, reported the human gut microbial composition in a population sample of 123 nonobese and 169 obese Danish individuals. Establishment of a catalog of bacterial genes from the human gut, the researchers said, encouraged them to ask whether variation in the gut microbiome at gene and species levels defines subsets of individuals in the adult population who are at increased risk of obesity-related metabolic disorders.

The abundance of known intestinal bacteria can be assessed, the authors said, by the mapping of a large number of sequencing reads from total fecal DNA onto a reference set of their genomes. This “quantitative metagenomics” approach was extended by the authors to assess the abundance of genes from the reference catalog in a cohort of 292 nonobese and obese individuals.

They found that two groups of individuals differed by the number of gut microbial genes and therefore, gut bacterial richness. Individuals with a low bacterial richness (23% of the population) were characterized by more marked overall adiposity, insulin resistance, and dyslipidemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals.

The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated comorbidities.

Probiotics

The implications individual microbiomes has, investigators discovered, clear implications for health and disease. Jeffrey Gordon, M.D., director of the Center for Genome Sciences and Systems Biology, Washington University School of Medicine, and his researchers in his laboratory at Washington University, who this August reported experiments introducing gut microbiomes from lean and obese humans into mice with some unexpected results, showed the bacteria could transfer characteristic of lean animals into obese animal, or prevent the development of obesity.

Several years ago, in another study, Dr. Gordon described two groups of beneficial bacteria that are dominant in the human gut, the Bacteroidetes and the Firmicutes. When Gordon’s team had 12 obese people follow either a low-fat or a low-carb diet to lose weight, the result was more Bacteroidetes and fewer Firmicutes—the profile of slim people. The more Bacteroidetes, the more weight the volunteers lost.

The scientists showed that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Their findings indicate that obesity has a microbial component, which might have potential therapeutic implications. But these findings, and relatively simplistic interpretations, helped fuel the frenzy to sell probiotics, rationally or not, despite Dr. Gordon’s clear statements about the importance of how the microbiome operates in relation to diet.

But according to Dr. Gordon, at the moment, a far more complicated picture has emerged than just ingesting the right bacteria. He says, “There’s an intricate relationship between our diet and how our gut bugs alternately affect us.”

“Cocktails of classic probiotics, which people have been trying for years, may have some benefit but the effect seems to be quite small,” says Dr. Relman. A targeted approach that manipulates specific species could be more effective, but, Relman adds, “I don’t think we’re there yet”.

Bacteria from Lean Humans Can Slim Obese Mice

A new study suggests that more complex interactions between diet, body mass, and gut microbiota underlie metabolic disturbances than previously thought.

 

·                                 Patricia Fitzpatrick Dimond, Ph.D.

        The mouse models employed in this study could be used to identify other aspects of how the human gut microbiota and our diets influence human health. [© Mirko Raatz - Fotolia.com]

Graduate student Vanessa Ridaura and colleagues at the Center for Genome Sciences and Systems Biology,University of Washington School of Medicine reported in the September 6 issue of Science that mice lacking bacterial colonies of their own that received gut bacteria from obese humans put on more weight and accumulated more fat than mice that were given bacteria from the guts of lean humans.

To directly test the influence of the human gut microbiome on obesity, the investigators sampled microbes living in the guts of human fraternal and identical twins, one of whom was lean while the other, obese. They introduced these microbes into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections.

“The first thing that Vanessa identified in these mice, which were consuming a standard mouse diet, was that the recipients of the obese twins' microbiota gained more fat than the recipients of the lean twins' microbiota,” Jeffrey Gordon, M.D., director of the Center and a co-author of the Science report, explained. Since, he said, the differences could not be attributed to the amount of food the mice consumed, “there was something in the microbiota that was able to transmit this trait. Our question became: What were the components responsible?"

To perform what Dr. Gordon called “The Battle of the Microbiota,” the investigators housed mice that had received microbes from a lean twin (Ln mice) with mice that were given microbes from an obese twin (Ob mice). “Mice—delicately put—exchange their microbes readily,” said Dr. Gordon, referring to coprophagia, or the consumption of feces.

When Ridaura and her colleagues housed Ln mice with Ob mice for 10 days, they discovered that the Ob mice—affected by their cage mates’ microbes—slimmed down, adopting the “leaner” metabolism of the Ln mice. Ln mice, on the other hand, appeared unaffected and maintained their own metabolism, they say. The “rescue” of mice from obesity was correlated with colonization of specific members of Bacteroidetes bacteria that were part of the Ln biota, and, importantly, was diet-dependent. Only those mice eating a low-saturated fat, high fruit and vegetable diet became colonized with the Ln–associated bacteria. These animals did not become obese.

These findings suggest that more complex interactions between diet, body mass, and gut microbiota underlie human metabolic disturbances than previously understood. The mouse models employed by investigators could be used to identify other aspects of how the human gut microbiota and our diets influence human health.

“We now have a way of identifying such interactions, dependent on diet, and thinking about what features of our unhealthy diets we could transform in ways that would encourage bacteria to establish themselves in our guts, and do the jobs needed to improve our well-being,” said Dr. Gordon. “In the future, the nutritional value and the effects of food will involve significant consideration of our microbiota—and developing healthy, nutritious foods will be done from the inside-out, not just the outside-in.”

The study appears in the September 6 issue of Science with the title, “Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice”.

Interesting Biotechnology Things!

We did not know of all these interesting facts by ourselves. We searched and found all these. Enjoy!

1.The Breen in Star Trek use starships with organic technology. The starship USS Voyager used bio-neural gel pack circuitry. Species 8472 used organic spacecraft.

2.The Yuuzhan Vong in Star Wars exclusively use organic technology and regard mechanical technology as blasphemy.

3. In the book/movie Jurrassic Park, biotechnology is also involved!

Ingen, the company which created Jurassic Park, created the dinosaurs from dinosaur gene sequences present in a fossilised mosquito trapped in a piece of amber, with certain sections being taken from frog DNA.

web.reed.edu/nsfaire/images/nsfaire_biology.jpg

4. Did you know that researchers have reversed the aging process in brain cells? They have successfully induced brain cells to revert back to neural stem cells.

5.Did you know that....

the Centers for Disease Control estimates that some 18 million courses of antibiotics are prescribed for colds each year even though colds are caused by viruses?

6. Did you know that scientists are making plans to build a device that will detect all life outside of Earth?

7. Did you know that researchers have restored sight to blind dogs by injecting them with a genetically engineered gene?

8. Did you know that scientists have produced bone from skin and gum tissue?

9. Did you know that researchers have devised a method of isolating and extracting specific brain cells from cadavers that are able to divide and develop into other types of brain cells?

Interesting facts on the development of biotechnology in India

                                                                                                      

i. To evolve integrated plans and programmes in biotechnology and biotechnology related manufacturing.

ii. Establishment of infrastructure support at the national level

iii. To evolve bio-safety guidelines for laboratory research, production and applications.

iv. To initiate scientific and technical efforts related to biotechnology.

v. To act as an agent of the government for import of new recombinant DNA based biotechnological processes, products and technology

Fun Facts About Biotech and Health Care

The End of Our World as We Know It
A group of viruses and bacteria recently got together and put Homo sapiens on the endangered species list.

Now we Know How He Got the Idea
The inventor of colonoscopy, before he invented colonoscopy, worked for the Internal Revenue Service.

Everything is Gene-Based Now
Researchers in Toledo (Ohio, not Spain) have identified the gene that determines whether you have an innie or an outie.

Perhaps Better than Coffee and Red Wine too
A new research study provided data indicating that basic health care is better medicine than laughter.

It's Worked Great for ADHD and RLS
The best way to sell a new drug or device is to convince people that they have a new disease.

If You Don't Get Sick at Work or on a Plane
One of the best places to catch an infection is in a hospital.

The Revenge of the Lab Rat
The FDA has announced that it will accept data from research on humans to determine the safety and efficacy of drugs to be used to resuscitate lab rats.

A Once in a Lifetime Opportunity
A general practitioner in Paducah, Ky., one day saw all his patients at the exact time of their appointments.

Dealing with Rowdy Neanderthal Children
Researchers believe that Neanderthal man developed the first medical device: an earplug made of sandstone.

And How Much Did This Research Cost?
New research carried out by optometrists and psychologists in Australia shows that motorists suffering from cataracts are less able to spot potentially dangerous hazards on the roads.

Fun Facts About Microbes

• Microbes first appeared on earth about 3.5 billion years ago. They are critically important in sustaining life on our planet.

• Microbes outnumber all other species and make up most living matter.

• Less than .5% of the estimated 2 to 3 billion microbial species have been identified.

• Microbes comprise ~60% of the earths biomass.                             

• Microbes drive the chemistry of life and affect the global climate.

• Microbial cycling of such critical chemical elements as carbon and nitrogen helps keep the world inhabitable for all life forms.

• Microbes generate at least half the oxygen we breathe.

• Microbes thrive in an amazing diversity of habitats in extremes of heat, cold, radiation, pressure, salinity, acidity, and darkness, and often where no other life forms could exist and where nutrients come only from inorganic matter.

• Microbes offer unusual capabilities reflecting the diversity of their environmental niches. These may prove useful as a source of new genes and organisms of value in addressing bioremediation, global change, biotechnology, and energy production.

• Microbial studies will help us define the entire repertoire of organisms in specialized niches and, ultimately, the mechanisms by which they interact in the biosphere.

• Diversity patterns of microorganisms can be used for monitoring and predicting environmental change.

• Microbes are roots of life's family tree. An understanding of their genomes will help us understand how more complex genomes developed.

• Microbial genomes are modest in size and relatively easy to study (usually no more than 10 million DNA bases, compared with some 3 billion in the human and mouse genomes).

• Microbial communities are excellent models for understanding biological interactions and evolution.

• Most microbes do not cause disease.

Biotech’s First Musical Instrument Plays Proteins Like Piano Keys
 

A biophysicist and composer have banded together to create a music box that turns biology into sound

By Nona Griffin and Daniel Grushkin

The chromochord holds 12 vials, each paired to a different electronic sound. Find out more in the Slide Show.Image: Karen Ingram (kareningram.com

First comes a cacophony of gongs, then flutters of chimes, then a deep melodic whale call—these are the sounds of the first musical instrument powered by biotechnology. The music comes from a black box in the home lab of Josiah Zayner, a biophysicist at the University of Chicago. Inside the box blue lights pulse on vials of proteins, which in turn trigger the sounds. Zayner calls it the chromochord. “Chromo” refers to the colored lights and “chord” refers to the strings of a musical instrument. Essentially, it’s light activated. “Scientists see beauty in a well-crafted experiment,” Zayner says. “The chromochord allows other kinds of people to experience that beauty.”

The chromochord relies on proteins fromplants that respond to sunlight, known as light-, oxygen- and voltage-sensing (LOV) proteins. Sunlight causes proteins in leaves and stems to expand, which sets off a cascade of cellular signals that allows plants to grow toward a light source. Zayner isolated LOV proteins from oats, collected them in vials and bioengineered each sample to react differently to blue light. “People don’t have the chance to consciously experience life on the cellular level,” says Zayner, who studies LOV protein activation and movement in his research. “This brings it smack-dab in their ears.”

The chromochord holds 12 vials, each paired with a different sound. When light shines on one vial the proteins inside swell, changing the wavelength they absorb. A sensor measures the change in absorption and cues the sounds. As one set of proteins slowly expands, the chromochord emits the deep thrum of a bass; as another setquickly shrinks, out comes the sound of glass chimes.

“There is something conceptually appealing about hearing the sounds of biological things,” says Jason Freeman, interim director of the Center for Music Technology at the Georgia Institute of Technology. “These proteins have their own music to them. People make music out of mold, nanoparticles or all kinds of things. There’s something intrinsically interesting about these projects because they’re seeking to make audible that which is normally inaudible to us, to reveal something that may be a little bit mysterious or invisible to us in nature.”

The first chromochord prototype had a push-button interface but Zayner found it unwieldy and finicky when he first played it at a physics conference in Berlin. Instead, he wanted to create a more portable and reliable device, so he partnered with composer Francisco Castillo Trigueros on a second version. The two met after Zayner sent a mass e-mail to composers at the local conservatory. “Francisco was the only one who responded,” Zayner says. Trigueros wrote the music and Zayner translated it into automated light pulses and built the machine.

The two make a surprising pair: Zayner has a lip piercing and a large cross tattoo on his chest, whereas Trigueros wears V-neck sweaters and collared shirts and is often mistaken for the scientist.

In May the collaborators had their first two-day musical installation at the University of Chicago. The room was dark and the sounds were eerily calming. On the front wall projections of deep-blue blobs morphed into one another, a visual representation of the sounds. But on the second day of the show the proteins began to stick together. The musical phrases turned into noise and the visuals faded. “The installation that we set up had beautiful music,” says Zayner, “but then over time the music would slowly be distorted as the proteins started to fail.”

The breakdown surprised Trigueros: “I had to rethink my role as a musician.” But it was Zayner’s intention. “In our bodies, there might be a million proteins in a cell. Some of them get damaged—things happen,” Zayner says. “In the end it’s not perfect, but it’s still beautiful almost because of that imperfection.”

Others seem to have agreed. “I think the audience was pretty enamored with it,” says Julie Marie Lemon, the program director and curator of the Arts|Science Initiative at the University of Chicago. “In a sense, the life of the protein was being experienced.”

Zayner and Trigueros next plan to create another musical instrument, this time using cells and sound, rather than light to stimulate them. They hope to expose bacterial and one day human cells to music and measure how the cells’ pressure-sensitive ion channels respond. When sound waves hit the channels, a surplus of ions floods through the cell and elicits a response that can be translated into new, different music. “This is just the seed, and we will see how the tree grows, but it could be really strange,” Trigueros says.