Obesity via Microbe Transplants

Germ-free mice gain weight when transplanted with gut microbes from obese humans, in a diet-dependent manner.

By Ed Yong | September 5, 2013

Escherichia coliWIKIPEDIAPhysical traits like obesity and leanness can be “transmitted” to mice, by inoculating the rodents with human gut microbes. A team of scientists led by Jeffrey Gordon from the Washington University School of Medicine in St. Louis found that germ-free mice put on weight when they were transplanted with gut microbes from an obese person, but not those from a lean person.

The team also showed that a “lean” microbial community could infiltrate and displace an “obese” one, preventing mice from gaining weight so long as they were on a healthy diet. The results were published today (September 5) in Science.

Gordon emphasized that there are many causes of obesity beyond microbes. Still, he said that studies like these “provide a proof-of-principle for ameliorating diseases.” By understanding how microbes and food interact to influence human health, researchers may be able to design effective probiotics that can prevent obesity by manipulating the microbiome.

The human gut is home to tens of trillions of microbes, which play crucial roles in breaking down food and influencing health. Gordon’s group and others have now shown that obese and lean people differ in their microbial communities. Just last week, the MetaHIT consortium showed that a quarter of Danish people studied had a very low number of bacterial genes in their gut—an impoverished state that correlated with higher risks of both obesity and metabolic diseases.

However, descriptive studies like these cannot tell scientists whether such microbial differences are the cause of obesity or a consequence of it. “A lot of correlations are being made between microbe community configurations and disease states, but we don’t know if these are casual or causal,” said Gordon. By using germ-free mice as living laboratories, Gordon and his colleagues aim to start moving “beyond careful description to direct tests of function,” he added.

“It’s extremely exciting and powerful to go from descriptive studies in humans to mechanistic studies in mice,” said Oluf Pedersen, an endocrinologist who was involved in the MetaHIT studies. “That’s beautifully illustrated in this paper.”

Gordon lab graduate student Vanessa Ridaura inoculated the germ-free mice with gut microbes from four pairs of female twins, each in which one person was obese and the other had a healthy weight. Mice that received the obese humans’ microbes gained more body fat, put on more weight, and showed stronger molecular signs of metabolic problems.

Once the transplanted microbes had taken hold in their guts, but before their bodies had started to change, Ridaura housed the two groups of mice together. Mice regularly eat one another’s feces, so these cage-mates inadvertently introduced their neighbors’ microbes to their own gut communities. Gordon called this the “Battle of the Microbiota.”

These co-housing experiments prevented the mice with “obese” microbes from putting on weight or developing metabolic problems, while those with the “lean” microbes remained at a healthy weight.

Gordon explains that the obese microbe communities, being less diverse than the lean ones, leave many “job openings” within the gut—niches that can be filled by the diverse lean microbes when they invade. “And obviously, those job openings aren’t there in the richer, lean gut community,” he said. “That’s why the invasion is one-directional.” 

“But if invasion is so robust, why then isn’t there an epidemic of leanness?” asked Gordon. “The answer appears to be, in part, diet.”

In her initial experiments, Ridaura fed the mice standard chow, which is high in fiber and plant matter. She also blended up two new recipes, designed to reflect extremes of saturated fat versus fruit and vegetable consumption associated with Western diets.

If the mice were fed food low in fat and high in fruit and vegetables, Ridaura found the same results as before—the lean microbes could cancel out the effect of the obese ones. But when the mice were fed food low in fruit and vegetables and high in saturated fat, those with obese gut microbes still gained weight, no matter who their neighbors were.

This may be because the best colonizers among the lean communities were the Bacteroidetes—a group of bacteria that are excellent at breaking down the complex carbohydrates found in plant foods. When the mice ate plant-rich diets, the Bacteroidetes could fulfill a metabolic role that was vacant in the obese gut communities. When the mice ate unhealthy, plant-poor diets, “these vacancies weren’t there and the organisms couldn’t establish themselves,” said Gordon.

“We’re now trying to identify particular sets of organisms that can do what the complete community does,” Gordon added. The ultimate goal is to create a set of specific bacteria that could be safely administered as a probiotic that, along with a defined diet, could help these beneficial microbes to establish themselves and might effectively prevent weight gain.

“This study is an inspiration for us at MetaHIT,” said Pedersen. “It would be very interesting to take stools or cultures from extreme cases within our samples—people who have very rich or very poor gut microbiomes—and inoculate them into germ-free mice. . . . Now that we have a proof-of-concept, it’s obvious for us to follow up our findings through these studies.”

V.K. Ridaura et al., “Gut microbiota from twins discordant for obesity modulate metabolism in mice,” Science, doi: 10.1126/science.1241214, 2013.

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Avatar of: somey


Posts: 8

September 6, 2013

Dr.Gordon is always respected---particularly for the experimental design and setup--as if Arithmetic of junior School. I am really his fan and consider myself so fortunate when go through articles like this. Regards to him.

Avatar of: J.W.Sherwood


Posts: 1

September 6, 2013

I seems to me that these findings show that diet influences weight and the profile of your gut microbes.  It think they are looking at things backward.

Avatar of: copernicus


Posts: 10

September 8, 2013

J W Sherwood, I agree.  The obese mice didn't loose weight when they were given good bacteria if they continued to eat rubbish.  Should be a red light shoudn't it?

But then, what they are looking for as an endpoint is an 'industry' product that you have to buy all the time to make money for the company, there is no point telling people that if they eat correctly the right food will change your gut flora to the same as skinny people. 

And why point out the blindingly obvious, that most obese people were... once skinny!  How did they get obese?  By bad nutrition changing their gut flora.

But Shhhhh... after spending all this money finding out what most of us knew already, to tell people to eat correctly in the first place, wouldn't pay for the research and earn some company big bucks would it?

Avatar of: Iwona Grad

Iwona Grad

Posts: 7

Replied to a comment from copernicus made on September 8, 2013

September 9, 2013

I disagree with the "industry conspiration theory". We are all adults, responsible for our actions and what happens? Everyone knows eating healthy is good for you. Does that make people eat healthy? Everyone knows caloric restriction has links to longevity. Does that make people eat less? On top of it, lots of people are dieting without any positive or long-lasting outcome. And that is not only because they have bed nutrition and are lazy. 

The mice fed THE SAME diet (which actually was low fat, high polysaccharide) turned obese or lean, depending on the microbiota they were given. This leads to a great potential in probiotics to help people fight obesity. What is wrong with that??? I am all pro healthy eating habits, but it is more complicated that just saying EAT HEALTHY you lazy one! And microbiota is one brick that could help people that wat to change the lifestyle but have difficulties doing so.

The results with eating rubbish-staying fat mice just meant to show that lean microbiota cannot invade stably in this condition. We do not know what would happen if we kept the lean-microbiota mice on fat diet for a long time (Well I just looked through the paper, perhaps the experiments were done?). And that could prove what is stronger - the microbiota or the diet. My guess is both are important so why don't we take advantage of the two?

Avatar of: madhupjoshimd


Posts: 16

September 10, 2013

This study & fecal transplant treatment being performed, for many years in Australia, might offer cures for many gut diseases as Crohns disease, IBD, TYPE II DM & many other ilnesses. 

Perhaps even psychiatric illnesses might be curable instead of just being managed by medications.

If only most Americans were less offended by rectal administration of necessary substances & the availability of pirified & non- infectious feeces. availability 

Avatar of: copernicus


Posts: 10

Replied to a comment from Iwona Grad made on September 9, 2013

September 11, 2013

I was being sarcastic and provocative Iwona.

I don't believe there is an industry conspiracy.  Long lasting outcomes only come with knowledge, convictions, willpower and determination.  Without those two things, even if the study above the fat mice given lean microbiota, who continued to eat junk food, stayed fat, and so it will  be with humans.  Taking responsibility means just that,... not looking for magic biotics, so that you can continue to have your "cake and eat it". . 

There continues to be scientific blindness surrounding the microbiota issue, not just on the microflora/ obesity issue, but the fact that the medical model still throws antibiotics around with impunity believing that they can get away with microbiota murder with no penalty, short or long term.  And before you want to argue, yes, Dethlefsen and other have woken up and published, but the majority of the public and prescribers stay selectively deaf and blind.

The fact is that the vast majority of obese people were skinny at one time. 

Then they became obese. 

That wasn't due to a sudden change in their microbiota, but "little bits of toe-nails (habits) wear away the socks", though some might be tempted to blame an antibiotic course.... 

There is nothing wrong with using microbiota to kickstart attitudinal changes, but the bottom line will always be that people have to, at some point, say, "I WILL change my lifestyle, and I WILL NOT go back to my past eating habits". 

The bottom line is and always has been, that what we eat forms the prebiotics, which feed the probiotics.  That is graphically illustrated in the difference of gut microbiome in breastmilk fed babies, compared to formula fed babies. That was first thoroughly researched in 1945 by Erik Olsen. The two microflora almost comprise species which are planets apart.  That's not the babies' fault, but the fault of the parents whose choices determined the outcome.

The problem with scientists today, is that there is an assumption that because they don't know something, that's because it was never studied before.  Since before antibiotics were around to napalm gut flora, it has been known that what you eat alters your intestinal garden.  The is a huge body of literature which should have raised all these questions eons ago, so it's not easy for those of us who own all this literature to read animal experiments reinventing the wheel, yet coming to skewed conclusions.

The "soil" in a garden is everything, but the soil is determined by how you build it up, the types of compost you put in, the mineral and ph balance etc, and the worms, millipedes etc.. the compost "workers".  And in that regard, gut flora conforms to the same rules.  Compost doesn't just happen.  Good gut floradoesn't just happen.  It has to be nurtured, fed correctly and looked after.

Bottom line is that this is NOT rocket science.  The literature has been there since Henry Tissier first discussed this in 1905, yet suddenly we're expected to think that this is the first blinding revelation of the obvious.... 

as Madhup intimates, putting another person's faeces into a fat person's intestines, might kick start positive results, but the long term lies in the top two inches above the eyes.



Avatar of: Luigiii


Posts: 1

April 6, 2014

I am no science expert whatsoever so i don't know if these is even a possible prospect to look at or even holds any true bearings of helping this research, but what about high protein low fat/high protein high fat/low fat/low protein/high filler like fiber? I don't really know much at all about just bumped into on facebook, but if it hasn't already been checked wouldn't looking at Ketosis at least offer some more incite and means of testing this? Should probably clarify further just for the sake of doing it, applying obese/lean microbes to each of these, and the low fat/low protein/high filler (this part may be utterly incorrect) to emulate a desperation diet, not sure what its called, mitoketosis or something of the sort i think? But on the more sadistic side of testing i suppose, but inducing the body to metabolize its own muscles

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