The logic behind weight-loss surgery seems simple: rearrange the digestive tract so the stomach can hold less food and the food bypasses part of the small intestine, allowing fewer of a meal's calories to be absorbed. Bye-bye, obesity.

A study of lab mice, published on Wednesday, begs to differ. It concludes that one of the most common and effective forms of bariatric surgery, called Roux-en-Y gastric bypass, melts away pounds not - or not only - by re-routing the digestive tract, as long thought, but by changing the bacteria in the gut.

Or, in non-scientific terms, the surgery somehow replaces fattening microbes with slimming ones.

If that occurs in people, too, then the same bacteria-changing trick achieved by gastric bypass might be accomplished without putting obese patients under the knife in an expensive and risky operation.

"These elegant experiments show that you can mimic the action of surgery with something less invasive," said Dr. Francesco Rubino of Catholic University in Rome and a pioneer in gastric-bypass surgery. "For instance, you might transfer bacteria or even manipulate the diet" to encourage slimming bacteria and squelch fattening kinds, said Rubino, who was not involved in the study.

For many obese patients, particularly those with type 2 diabetes, gastric bypass has succeeded where nothing else has. Severely obese patients routinely lose 65 to 75 percent of their excess weight and fat after the operation, studies show, and leave their diabetes behind.

Oddly, however, the diabetes remission often occurs before significant weight loss. That has made bypass surgeons and weight-loss experts suspect that Roux-en-Y changes not only anatomy but also metabolism or the endocrine system. In other words, the surgery does something besides re-plumb the gut.

That "something," according to previous studies, includes altering the mix of trillions of microbes in the digestive tract. Not only are the "gut microbiota" different in lean people and obese people, but the mix of microbes changes after an obese patient undergoes gastric bypass and becomes more like the microbiota in lean people.

Researchers did not know, however, whether the microbial change was the cause or the effect of post-bypass weight loss.

That is what the new study, by researchers at Massachusetts General Hospital and Harvard University, set out to answer.

They first performed Roux-en-Y on obese mice. As expected, the animals quickly slimmed down, losing 29 percent of their weight and keeping it off, the researchers report in the journal Science Translational Medicine.

To make sure there was not something about the general experience of surgery, rather than gastric bypass specifically, that affected the animals, the scientists performed sham Roux-en-Y on other obese mice. In this procedure, the researchers made incisions as if they were going to do a gastric bypass, but instead connected everything up as nature had it.

The researchers then transferred gut microbiota from the Roux-en-Y mice to microbe-free obese mice. Result: the recipient mice lost weight and fat - no surgery required. Crucially, obese mice that received gut bugs from mice that had received sham Roux-en-Y, not the real thing, did not slim down.

It is the first experimental evidence that changes in the gut microbiota cause the weight loss after gastric bypass, and that the new, post-bypass mix of microbes can cause weight loss in animals that did not have surgery.

In particular, just a week after surgery the Roux-en-Y mice harbored relatively more of the same types of bacteria that become more abundant in people after gastric bypass and that lean people have naturally.

"The effects of gastric bypass are not just anatomical, as we thought," said Dr. Lee Kaplan, senior author of the study and associate professor of medicine at Harvard Medical School. "They're also physiological. Now we need to learn more about how the microbiota exert their effects."

Slimming bacteria work their magic in either of two ways, studies of gut microbiota show. They seem to raise metabolism, allowing people to burn off a 630-calorie chocolate chip muffin more easily.

They also extract fewer calories from the muffin in the first place. In contrast, fattening bacteria wrest every last calorie from food.

Transferring slimming bacteria into obese people might be one way to give them the benefits of weight-loss surgery without an operation. It might also be possible to devise a menu that encourages the proliferation of slimming bacteria and reduces the population of fattening bacteria.

Another new study published this week found people might be able to find out if they have slimming gut germs or fattening one using a breath test.

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• Amazing results after weight loss surgery
• Could weight loss surgery end diabetes?

AP

A clump of Staphylococcus epidermidis bacteria (green) in the extracellular matrix, which connects cells and tissue, taken with a scanning electron microscope. At right, the bacterium Enterococcus faecalis, which lives in the human gut, is just one type of microbe that live on your skin, up your nose, in your gut; enough bacteria, fungi and other microbes that collected together could weigh a few pounds. (AP Photo/National Institute of Allergy and Infectious Diseases (NIAID, Agriculture Department)

Could antibiotics make you fat?

Two studies this week suggest that using antibiotics may save people’s lives, but could also change their metabolisms. Put together, the studies suggest that taking antibiotics might alter digestion to help people absorb calories from food they normally would be unable to digest.

Every human carries pounds of microorganisms that we couldn’t live without. They break down food and extract nutrients like Vitamin K for us. Antibiotics will kill some of these beneficial organisms, which is why so many doctors now tell patients to eat yogurt after taking a course of the drugs, to replace some of the good guys.

“There is emerging evidence suggesting the importance of the microbes in our intestines and their role in absorbing food,” said Dr. Leonardo Trasande of New York University, who led one of the studies.

The two studies look at different sides of the coin, and help answer two questions -- whether antibiotics really do affect how we absorb nutrients, and how they might do so. Together, they support the idea that the drugs kill off some populations of bacteria and allow microbes to flourish that are very good at getting calories out of hard-to-digest plant foods.

Trasande’s team looked at the medical records of more than 11,000 newborns in Britain, who were carefully followed after they were born in the 1990s. The babies who got antibiotics before they were 6 months old were 22 percent more likely to be overweight by the time they were 3 years old, the team reported in the International Journal of Obesity. If they got antibiotics later in childhood, there wasn’t a strong effect – something that could suggest the antibiotics changed the balance of the microbes as they were just setting up shop in the infants. Babies are born with sterile digestive tracts, and they acquire bacteria, yeast and other microorganisms mostly from their mothers. The germs are collectively called “flora” by scientists.

“They play key roles in immune functions, among other things,” Trasande told NBC News. “Antibiotics disrupt the development of the healthy flora in our gut. The earlier the exposure occurs, the more disruptions occur,” Trasande says. “It seems the first few days and months are important. It is difficult to reconstitute that in later life.”

The other piece of the puzzle is whether it’s the antibiotics or something else that is doing this. Dr. Martin Blaser of New York University has been studying the effects of antibiotics on the body for years. A second team he heads has been studying what happens if you feed antibiotics to animals.

They wanted to replicate what farmers have known for decades -- that giving low doses of antibiotics to farm animals make them fatter. Many experts had thought the drugs were keeping the animals from getting infections and making them healthier, but Blaser suspected something else was going on.

When his team gave mice low doses of antibiotics long-term, the mice got fatter even though they weren’t eating any more than other mice. This, they report this week’s issue of the journal Nature, suggests the antibiotics somehow make the mice absorb more calories from their food.

“We have other work that is in process that continues to confirm and extend this,” Blaser said. “That work shows that giving antibiotics early in life, similar to what farmers do in their farm animals, is changing metabolism in mice and making them bigger and fatter.”

The gastrointestinal tract is also the center of hormone production, the researchers said. It’s possible altering the organisms in the intestines – called the microbiome -- could help people better absorb nutrients and calories from “indigestible” foods such as cellulose.

The second NYU team gave the mice varying combinations of the antibiotics penicillin, vancomycin and chlortetracycline. Mice that got the antibiotics piled on more fat than other mice, even though the fatter mice did not eat more. Also, their poop had fewer calories – suggesting they were absorbing more and eliminating less.

Other mouse studies being done by Blaser’s team show that giving antibiotics to mice every once in a while -- akin to giving antibiotics to a child to treat ear infections -- also alter the gut bacteria.

So does that explain why people are getting fatter? Does every dose of antibiotics kill off some bacteria, allowing the energy-efficient species to move in and squeeze every calorie out of an apple peel or bowl of high-fiber cereal?  

“That’s at least one of the mechanisms,” says Blaser. But he notes that studies in people suggest it’s doses very early in life that matter most, just as various colonies of bacteria are getting established in the colon and intestines. And there’s an effect on the immune system, too. Other studies show that changing the balance of bacteria effects immune cells known as T-cells – something that may someday help explain links between diet and diseases such as inflammatory bowel diseases and perhaps even colon cancer.

In other words, it is too soon to say whether a 5-day prescription of Zithromax for strep throat could make you fat.

“A lot of things are interconnected,” Blaser says. “Obesity is multifactorial. I am not saying antibiotic effects on the microbiome are everything but our work suggests it is contributory. Whether it’s 10 percent or 70 percent, we don’t know yet.”

Another big missing piece of the puzzle: Which species of bacteria are the most important? People have trillions of bacteria in and on their bodies. Microbes outnumber human cells by a factor of at least 10 to one and scientists believe at least 10,000 different species live in and on us. Healthy colonies of microbes not only process vitamins, but maintain pH balance on the skin, prevent tooth decay and even protect against infections. So which ones are killed by the antibiotics, and which do we want more of? No one knows yet.

“We are just beginning to scratch the surface,” said Dr. Ilseung Cho, who worked on the study in mice.

While it is important not to use antibiotics when they are not needed, the researchers stress that they do save lives. “I wouldn’t rush to come off any antibiotics right now,” Cho cautioned.

It’s also not clear if food like yogurt, called probiotics, help much. “There is a concept called prebiotics,” Cho said. “It is essentially introducing nutrients into your digestive tract that would select for particular bacteria. Then you might be able to alter the bacteria.”

Prebiotics are found in plain old food such as soybeans, jicama and raw oats, all of which are rich in compounds such as inulin, which people cannot digest, but which certain bacteria love.

Related links:

• Mapping one man's microbes
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• Ruled by your gut

Photo courtesy Charles Rathmann

Charles Rathmann, 40, a St. Louis research director was the first of 242 volunteers accepted for a research project that collected samples of their cells to map the microbial make-up of healthy humans.

Charles Rathmann never thought of himself as a model for American manhood, but when it comes to the bugs on his body, he is.

The 40-year-old St. Louis research director is among 242 volunteers whose skin, nose, mouth, gut and other samples have been collected and analyzed to create what scientists are celebrating as the first map of the normal microbial make-up of healthy humans.

“I am an ordinary guy,” Rathmann told msnbc.com. “But they can use the normal flora on my body to set a baseline.”

Indeed, the release of coordinated research Wednesday from the Human Microbiome Project Consortium organized by the National Institutes of Health promises to revolutionize the study of the microorganisms that inhabit people, experts told reporters.

"This is a whole new way of looking at human biology and human disease," said Dr. Phillip Tarr, a researcher and professor of pediatrics at the Washington University School of Medicine. "It's awe-inspiring and it also offers incredible new opportunities."

Instead of the one-germ, one-disease theory that has governed past thinking, doctors and patients alike will need to consider the entire ecosystem of bacteria at work in the body, much like the ecosystem of a forest in nature. 

"This is going to be a whole new ballgame," Tarr added. 

Scientists are just starting to use the new HMP data to understand disease, including the role of the gut microbiome in maladies such as Crohn's disease or ulcerative colitis, the skin microbiome in psoriasis, and the urogenital microbiome in reproductive and sexual diseases, among many other projects, experts said. It could become crucial in figuring out remedies for serious and potentially deadly C. difficile infections, which are blamed on disruptions in the normal flora of the gut, Tarr said.

Scientific reports being published this week include two in the journal Nature and 12 in journals from the the Public Library of Science or PLoS. The reports represent work from some 200 members of the HMP Consortium from nearly 80 universities and scientific institutions reflecting five years of research, according to the NIH.

For the first time, researchers used sophisticated genome sequencing techniques to find that instead of the few hundred bacterial species previously identified through laborious cultures, there are more than 10,000 microbial species inhabiting the human body.

Microorganisms outnumber human cells 10 to 1 and they make up between 1 percent and 3 percent of the body’s mass, the researchers found. In a 200-pound adult, that means there are between 2 pounds and 6 pounds of bacteria, "a rather remarkable amount," said Dr. Eric D. Green, director of the National Human Genome Research Institute. 

The new data, which will provide a shared database for the scientific community, showed that people harbor a whole range of microbes, including beneficial bugs and also pathogens known to cause disease. The microbes in healthy people appear to be much more diverse from site to site than expected, and also from person to person, researchers found. In addition, they were surprised to learn that the specific bacteria at a site are less important than the functions they perform. 

"It appears that bacteria can pinch-hit for each other," Curtis Huttenhower, a researcher at the Harvard School of Public Health explained in a statement. He was co-lead author of one of the HMP papers published in the journal Nature. 

Information like that is exactly why Rathmann agreed to be scraped, poked and prodded for science.

“I liked the fact that this was going to be a way for them to learn more about these little bacteria that exist invisibly on us,” he said.

Researchers collected a total of 5,298 samples, plucking them from up to 18 body sites of Rathmann and the other volunteers, including 129 men and 113 women, from Houston and St. Louis.

Photo courtesy National Institutes of Health

This gut bug, the bacterium Enterococcus faecalis, is among those analyzed through novel genome sequencing techniques as part of the Human Microbiome Project Consortium coordinated by the National Institutes of Health.

Participants included some of Rathmann’s friends and colleagues, even his ex-wife, in part because Rathmann’s actual job is to round up subjects for clinical trials at the Washington University School of Medicine.

“My group tries to recruit volunteers,” said Rathmann, who is director of the Recruitment Enhancement Core at the WUSM Center for Clinical Studies.

“We get involved any time we see a trial that is interesting. It helps move the medical community forward.”

In this case, Rathmann and the others had to prove they were healthy, undergoing screening tests, blood tests, even dental exams to make sure their microbes weren’t unusual.

“If you had a cavity, you were out,” he said. “You could take no medicines that would disrupt the flora they were trying to identify.”

The samples were collected over a period of several weeks starting in 2009, when Rathmann and others had to agree to use study-issued shampoos, soaps and toothpastes during the testing period.

The actual collection of the microbes was simple and not painful, Rathmann said. It involved scraping cells from 15 sites in men and 18 sites in women, who had vaginal swabs taken from three places.

“It was the mouth, teeth, back of the throat, inside of the elbow, back of the ear,” Rathmann recalled. “You also had to give a stool sample on two or three different occasions.”

Researchers took these samples, all from adults ages 18 to 40, then analyzed them using a novel genetic sequencing technique that was able to identify the DNA of bacteria, ignoring the normal human DNA.

Using computers, the scientists sorted 3.5 terabytes of data to get a full picture of the human microbiome, the collection of microorganisms living in the human body.

What they found was riveting, reported the scientists, who figure they’ve now identified between 81 percent and 99 percent of all genera of microorganisms in healthy adults.

One paper published in PLos ONE found that there were certain core bacteria present in 95 percent of all subjects. But even among those core bacteria, there was a wide range among sites -- and among people. 

"Our findings include the fact that humans carry a remarkable range of microbes," said Bruce Birren, director of the Genomic Sequencing Center for Infectious Diseases. "Apparently there are many different ways to be healthy when it comes to our microbes."

Launched in 2007, the HMP has been funded through $153 million from the NIH Common Fund, which invests in high-impact research, and another $20 million from individual NIH institutes and research centers. 

Until today, Rathmann had not seen any of the research associated with his body samples. Participants didn’t receive maps of their individual microbiomes and they have no idea what particular bugs they harbored in various places.

“I definitely will follow the results of this,” said Rathmann, who hopes his example will prompt others to volunteer for clinical trials. “Our flora will be the benchmark now for what everybody studies.”

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