Pathogen from gut of obese human causes obesity in germfree mice

http://www.nature.com/ismej/journal/vaop/ncurrent/full/ismej2012153a.html

by not_that_noob • 14 years ago

131 129 14 years ago

danesparza• 14 years ago

The article is very interesting. I looked, but couldn't find information on the exact diet of the test subject during the study. Did anybody else have any better luck?

gte910h5• 14 years ago

The supplementary information link at the bottom has a link to the diet and how it was prepared:

Dietary intervention and sampling. This volunteer was given a diet composed of whole grains, traditional Chinese medicine and prebiotics (WTP diet) for intervention. He was given 4 cans of gruel per day as staple food contract prepared in the form of cooked porridge (370 g wet weight per can) then canned by a food manufacturer (Shanghai Meilin Meida Food Co., Ltd.) for 23 weeks. Each can contained 100 g dry ingredients (59 g of carbohydrate, 15 g of protein, 5 g of fat, and 6 g of fiber) providing 336 kcal energy (70 % of carbohydrate, 17 % of protein, 13 % of fat). Fresh fecal samples were collected with 4 or 5 weeks intervals. Whole blood and serum samples were collected with 0, 9 and 23 week (0d, 9w, 23w). All samples were immediately frozen on collection and stored at -80 °C for subsequent analysis.

DenisM• 14 years ago

So, only 1344 cals per day.

sixdimensional• 14 years ago

Is it just me or isn't that basically what they feed you in the Matrix?

"Tank: Here you go, buddy; 'Breakfast of Champions.' Mouse: If you close your eyes, it almost feels like you're eating runny eggs. Apoc: Yeah, or a bowl of snot. Mouse: Do you know what it really reminds me of? Tasty Wheat. Did you ever eat Tasty Wheat? Switch: No, but technically, neither did you. Mouse: That's exactly my point. Exactly. Because you have to wonder: how do the machines know what Tasty Wheat tasted like? Maybe they got it wrong. Maybe what I think Tasty Wheat tasted like actually tasted like oatmeal, or tuna fish. That makes you wonder about a lot of things. You take chicken, for example: maybe they couldn't figure out what to make chicken taste like, which is why chicken tastes like everything. Apoc: Shut up, Mouse."

http://www.imdb.com/title/tt0133093/quotes?qt0324288

psycr• 14 years ago

Two interesting notes from the abstract:

"The endotoxin-producing Enterobacter decreased in relative abundance from 35% of the volunteer’s gut bacteria to non-detectable, during which time the volunteer lost 51.4 kg of 174.8 kg initial weight and recovered from hyperglycemia and hypertension after 23 weeks on a diet of whole grains, traditional Chinese medicinal foods and prebiotics."

"The obesity-inducing capacity of this human-derived endotoxin producer in gnotobiotic mice suggests that it may causatively contribute to the development of obesity in its human host."

indiecore7• 14 years ago

Great, another article for fat acceptance idiots to read the title of and declare it cake day.

> The volunteer lost 30.1 kg after 9 weeks, and 51.4 kg after 23 weeks, on a diet composed of whole grains, traditional Chinese medicinal foods and prebiotics (WTP diet, Supplementary Information; Supplementary Figure 1), with continued amelioration of hyperinsulinemia, hyperglycemia and hypertension until most metabolic parameters improved to normal ranges (Table 1). After 9 weeks on the WTP diet, this Enterobacter population in the volunteer's gut reduced to 1.8%, and became undetectable by the end of the 23-week trial, as shown in the clone library analysis (Table 1; Supplementary Figures 2 and 3).

panzagl• 14 years ago

You're right, we should all lament the possible passing of another way of judging people inferior to us.

ChuckMcM2• 14 years ago

He missed the part where Monsanto makes a weaponized form of the bacteria that you use against your enemies to make them fat.

indiecore7• 14 years ago

I don't care if someone is fat. What I care about is the loons saying that it's healthy and fine to be morbidly obese and they use stuff like this to back it up.

"Gut bacteria are the cause, I can do nothing"

"It's genetics"

No, it's calories in vs calories out. Maybe these bacteria make you want to eat more, maybe they somehow pull more energy out of food than normal gut flora somehow, in the end it doesn't really matter. Eat less, lose weight; eat more, gain weight; the definition of 'more' and 'less' are individual.

ChuckMcM2• 14 years ago

Ok, this is an interesting observation:

"After 9 weeks on the WTP diet, this Enterobacter population in the volunteer's gut reduced to 1.8%, and became undetectable by the end of the 23-week trial"

So the thesis is that this bacteria lives in obese people's gut, and it makes them more obese. But once they diet to a point where they are not obese, the bacteria dies off? I wonder if they are going to try a diet + anti-biotic treatment, diet + placebo trial on two obese patients to see if it improves their chances to get back into a regular balance.

acgourley• 14 years ago

For people who didn't read the summary - that patient who lost 30kg and reduced their bacteria population was on anti-biotics. So, right, it would be interesting to see if that bacteria reduces without the anti-biotics.

But before you think the researchers left a big hole in their research, remember that the addition of bacteria makes mice obese. Now if we could just try that on humans...

edit: As pdx points out below, not antibiotics, pre-biotics. Big difference.

pdx• 14 years ago

The patient was not on antibiotics, he was on prebiotics. So, this is something you could do yourself without a doctors cooperation.

Able7• 14 years ago

No antibiotics were involved but the WTP diet consisted of 1344Cal daily diet of canned porridge (. . ."4 cans of gruel per day" . . .) - Quoted from 'Supplimental Material' to the original study publication http://www.nature.com/ismej/journal/vaop/ncurrent/extref/ism.... But, there is absolutely no specific information as to the actual ingredients of the "porridge/gruel" so there seems to be no way to actually repeat this research or try the diet individually.

msarvar• 14 years ago

So they basically put him on a strict low calorie diet, and he lost weight? No way!

tarice2• 14 years ago

But once they diet to a point where they are not obese, the bacteria dies off?

I believe the theory is the reverse - by killing off the bacteria, the person becomes less obese.

Anti-biotics probably won't work as well as you hope because they kill all the bacteria in the gut - good and bad - which will just create more digestive problems.

im3w1l• 14 years ago

Poop transplants. Sounds gross, but can apparently work.

robbbaxley• 14 years ago

I have just finished reading the entire report including the supplement. It seems that the reason this bacteria was killed off is that the diet changed the pH balance in the gut. The report mentions "Bitter Melon" as killing the bacteria (Supplementary Figure 1. Bitter melon markedly modulated the human gut microbiota in in vitro experiment) Supplementary document, page 33. I couldn't find an exact reason for the subject taking the pre-biotics but I would suspect that it is to help re-colonize the gut with 'good' bacteria.

schoper• 14 years ago

ISME Journal.

1. Two independent facts from the experiment: A pathogen that causes obesity (in mice) seems to be active in some obese humans.

2. Severely restricted diet seems to powerfully reduce the population of this organism.

I doubt that these facts are unrelated. It's classic host-parasite behavior. The pathogen depends on high calorie intake in its host, and therefore engineers that behavior (somehow).

Further there is no reason to make the leap that the only or best way to counter this pathogen is through diet. It's not impossible that a targeted antibiotic that eliminates this pathogen would have an effect on the body composition of the host.

not_that_noob4• 14 years ago

Very interesting observation re parasitic behavior. I suspect that with modern food processing techniques to make food relentlessly cheaper, we have unwittingly enhanced the food supply for the parasite.

chc• 14 years ago

It's not really unwitting. Anything that increases nutrition for humans necessarily increases the food supply for creatures that prey on humans. Similarly, boosting the rabbit population enhances the food supply for creatures that prey on rabbits.

michaelbrave• 14 years ago

They could probably make a targeted antibiotic, but gut bacteria are something not very well understood yet, and it's a highly complex ecosystem (some would say more complex than our own cells) that differs significantly from person to person.

they have done studies though to see if doing a guy bacteria transplant from a healthy person to an obese person would change their weight, I believe there wasn't any difference found for weight loss but that there was some hope in using it as a treatment for diabetes. I'd have to look it up.

This particular study though I wonder if it was the calorie restriction, the weight loss or the content of the diet that caused the changes to happen.

jack-r-abbit3• 14 years ago

I can comprehend a good deal of code but this medical jargon is making my head spin. Anyone care to summarize this for us feeble minded laypersons? Because it sounds like they found something in obese people that if eliminated could lead to weight loss. I know there are people that can benefit from that when extreme obesity makes regular, "simple" dieting very challenging and exercise impossible.

not_that_noob4• 14 years ago

tl;dr: fat guy lost a ton of weight by a diet that reduced a specific kind of gut bacteria; this bacteria inserted into mice engineered to be thin caused the mice to gain weight.

Ergo, bacteria may be driving obesity.

jack-r-abbit3• 14 years ago

So in theory, if a pill was developed to just kill that bacteria, fat guy loses weight.

fernly2• 14 years ago

Not only obesity, but insulin resistance: basically gave the mice the start of "metabolic syndrome", as also observed in obese humans.

icey• 14 years ago

It paints this animation of the spread of American obesity in a new light: http://en.wikipedia.org/wiki/File:BRFSS_obesity_1985-2006.gi...

hcarvalhoalves3• 14 years ago

Epidemic?

debacle3• 14 years ago

Someone made a comment yesterday on another site about how we are still living in the bacterial age.

It's a strange notion, that bacteria still own the earth, but we are host to more bacteria than we are our own cells. It's such an interesting yet scary thing to think about - does higher order life exist solely as vessels for bacteria propagation?

nlh• 14 years ago

Mind-bending, eh?

It's not too scary a though though -- taking the evolutionists point of view, there is no "underlying" reason that higher order life exists. It exists because the processes of natural selection have enabled it to exist and reproduce.

If bacteria contribute to the survival and reproduction of our species (they do), then they are simply part of the process. It goes both ways. We exist and reproduce because they help us do so, and they exist because we provide a nice host. One hand washes the other...

npsimons• 14 years ago

How's that saying go? 'Life - the whim of a few billion cells to be you for a while'.

marshray3• 14 years ago

Well bacteria are a lot smaller than our own cells, so comparing them by count doesn't seem very meaningful.

debacle3• 14 years ago

By mass, bacteria is still the dominant lifeform on earth.

splatcollision3• 14 years ago

Gut bacteria are an extremely powerful system within our bodies and are mostly still mysterious to us. Imbalances of one type or another lead to large amounts of bacterial toxins being introduced to the intestine and the bloodstream, with wide-ranging mental and physical effects. I'm not surprised that contribution to obesity is among them.

It works kind of like this:

You eat too much refined/processed food, that is high in sugars of any kind, especially complex polysaccharides and the food is not fully digested by your stomach + small intestine, and ends up in your large intestine. This surplus of sugars provides abundant food to your billions of gut bacteria, and they start to grow out of control, and mutate. Those mutated bacteria now dump their toxic waste by-products into your body.

Following restricted diets that are intended to reduce the food supply to your gut bacteria colonies is a valid and often the only successful way to treat the conditions caused by this influx of bacteria and toxins.

Antibiotics of any kind are simply too broad a weapon - they will attempt to eliminate everything which will result in other imbalances. The food we eat every day is the most important factor for intestinal and therefore overall health...

[1] This book is helpful: http://www.breakingtheviciouscycle.info

jbattle• 14 years ago

I thought the problem with refined/processed foods was that they were too easy for our bodies to absorb. Or is that true, but the amount consumed still results in a lot of 'leftovers'?

splatcollision3• 14 years ago

Yeah that seems a little counterintuitive at first, but your assumption is correct. You still absorb lots of cheap calories from the sugars / carbs that you eat, but there's still plenty of leftovers for the bacteria. Everyone's different though - some people may have no issues at all, others are extremely sensitive.

Alex39173• 14 years ago

"[the pathogen] can induce obesity and insulin resistance via an inflammation-mediated pathway"

This is why weed reduces one's risk of diabetes and also often helps obese people lose weight.[1] For what it's worth, you can now actually (supposedly) buy CBD (supposedly) legally online:

http://dixiex.com/

CBD is one of the more common non-psychoactive cannabinoids in marijuana, and it is responsible for many of the anti-inflammatory benefits. While more research is needed, lots of people are reporting the same sorts of benefits that this research is reporting, but without the obvious negative side effects of taking anti-biotics. (Whether there are negative effects of longterm CBD use is anyone's guess, but as far as I know nothing has been discovered so far.)

[1] http://blog.norml.org/2012/12/12/study-cannabis-associated-w...

splatcollision3• 14 years ago

Great points. The sooner this medicine can be freely accessible and available to all the better.

gamache2• 14 years ago

CBD is most definitely psychoactive. It also accounts for about 25-50% of marijuana's active components, so we are living in a world full of long-term data.

Cannabidiol is most definitely illegal in the US, too. That DixieX site you link to is just hemp oil products -- no psychoactives.

jonnathanson2• 14 years ago

Tangential, but: is the whole obsession with fiber a bit misguided? If polysaccharides are largely responsible for feeding gut bacteria (good and bad), and your link recommends cutting them out, then by definition, we should be cutting out dietary fibers (most of which are polysaccharides). Fiber is mostly undigestible in our stomachs and upper GI tracts, but is readily fermented by (and feeds) intestinal bacteria.

Or am I missing something here? Someone with a bit more knowledge of organic chemistry and biology can feel free to chime in here.

sliverstorm• 14 years ago

Most people are not aware that "fiber" is really just chains of sugar. I suspect this is where a lot of conflicting advice comes from.

hcarvalhoalves3• 14 years ago

The fiber helps your bowels work correctly. We were not created to evacuate bricks. You don't need a PhD in organic chemistry and biology to understand that, just experience with babies.

Steqheu2• 14 years ago

This is one of the first times I've heard such a confident voice of reason regarding this topic in such a liberal atmosphere. Thank you.

checker2• 14 years ago

Forgive my naivete (I have a passing knowledge about diet), but isn't 'complex polysaccharides' more or less a synonym for 'complex carbohydrates' (excluding oligosaccharides)? I feel that most readily available refined/processed food is low in complex carbs since the processing breaks them down, and because simple carbs are cheaper and taste better.

Essentially my question is this: A fresh vegetarian diet is going to be high in the complex polysaccharides that you mention. So why are vegetarians statistically thinner than the average population, if these complex polysaccharides are wreaking havoc on their digestive systems?

This whole question breaks down if I'm mistaken about the definition of complex polysaccharide. Thanks.

Udo7• 14 years ago

You are correct to doubt the meaning of these words as they are being flung around for the sole reason of providing credibility. Your mistake is coming with scientific thoughts into a discussion that is utterly non-scientific and purely based on making money with buzzword-laden books by turning anything related to food into a weird cult-like experience.

But at least your questions are in an area where I can maybe help out. Carbohydrates are just what the name says: carbon molecules with hydrogen and oxygen attached to them. Complexity of carbohydrates is a spectrum, with formaldehyde being at one end and ultra-complex molecules such as huge amino-saccharides or polymers on the other. Saccharides are sugars, who all belong to the carbohydrate family. As far as nutrition is concerned, most sugars are based on the glucose molecule, that's a unit with 6 carbon atoms typically wound into a ring with six or five edges. Chaining those rings together makes polysaccharides.

Overly long saccharide chains only fit into our sweetness taste detectors at one point, that's one ping each from a huge number of saccharide rings. Smaller sugars (like dextrose) cause a lot more signal by fitting better into the detectors, that's why they tend to taste sweeter. Polysaccharide disassembly starts with enzymes in the saliva of the mouth, that's why some things get sweeter when you chew on them for a while. For people who don't gobble down their food to quickly, that means only small sugar molecules even arrive in the small intestine, where they are further split into monosaccharides which can finally be resorbed through the intestinal wall. The small intestine is ill-equipped to handle longer chains, though, that's why they pass into the large intestine. In itself that's not a problem, but if there is a _regular and large_ amount of this stuff in the large intestine, it will attract microbes that live off it.

So if a lot of sugars regularly make it into the large intestine, chances are there will be a population of bacteria (or worse: funghi) taking advantage of that. It's not like the bacteria cause obesity as some articles suggest, their presence is itself a symptom of a nutritional problem (such as too much intake). Of course sometimes these colonies cause other problems like inflammatory reactions that eventually necessitate flushing them out. But saying those bacteria cause obesity is just the new "I'm not fat, I'm big boned", a mechanism designed to deflect the responsibility for obesity away from a person's behavior.

The digestive system is designed to survive and thrive on a variety of food, but there is also a lot that can go wrong. It's not "evil complex polysaccharides" wreaking havoc and producing energy out of thin air to make people fat, it's (as always) people eating too much who are bringing this upon themselves.

One good thing food cults such as the different "nutrition plans" and "strategies" can do, however, is making people reflect on their habits and generally lower their energy consumption. To make it extra clear: I don't think vegetarianism is one of these cults, but it too causes people to eat more carefully.

tarice2• 14 years ago

I've also heard that eating smaller meals, more regularly, can help your body lose weight.

This trend correlates well with the above idea, since smaller meals means that the sugars should be absorbed before the large intestine, thereby further robbing the bacteria of their food.

It would also explain the opposite effect - that eating larger meals makes losing weight harder, since the larger quantity of food has a better chance to get to your large intestine.

wildranter• 14 years ago

I went straight to the food list. They lost me at coffee should be VERY weak. They can't take that away from me! :)

Roshini• 14 years ago

No. It is pretty much impossible to overload your body's ability to absorb carbohydrates without a) exploding your stomach or b) you have some other health problem. By the time the food you eat gets to the bacteria, there are no sugar, fat or protein left. We absorb it all. We store extra of the first two and excrete the third (in a modified form) through urine.

Refined/processed food should be eaten in minimal quantities because it spikes blood sugar and causes insulin fatigue, which in the long run causes Type II diabetes.

And I'm in medical school, so yes, I do know what I'm talking about.

pnathan• 14 years ago

> Refined/processed food should be eaten in minimal quantities because it spikes blood sugar and causes insulin fatigue, which in the long run causes Type II diabetes.

What precisely does refined/processed food mean, from a chemistry standpoint? Is there a particular common process that transforms my homegrown lettuce into "refined lettuce"?

beswift• 14 years ago

>By the time the food you eat gets to the bacteria, there are no sugar, fat or protein left

You realize those bacteria are living off the fat, sugar and protein you consume right? They are essential to our ability to utilize the chemicals we get from these macro nutrients.

>Refined/processed food should be eaten in minimal quantities because it spikes blood sugar and causes insulin fatigue, which in the long run causes Type II diabetes. True, but this also an increasingly old school and one dimensional way of thinking about how type II develops. There are a host of genetic and environmental factors that effect an individual's response and eventual tolerance to insulin.

Sadly, being in med school does not guarantee you "know what you're talking about", in fact, even after you get to wear that white coat you'll probably realize you know way less than you could ever imagine. The perception that kind of attitude creates only narrows our minds and hurts our patients.

I'm done with med school.. and I realize on a daily basis I still have no clue what I'm talking about :)

anonymous• 14 years ago

Interesting how the book in your link disallows all whole grains, while the linked article specifically point out that the patient's diet consisted of "whole grains, traditional Chinese medicinal foods and prebiotics".

They also disallow milk, but allow cheese. My ancestors didn't spend thousands of years evolving lactose-tolerance for nothing, you know.

tlb• 14 years ago

You can pre-order a kit to get your intestinal biome mapped for $69. See http://www.ubiome.com/

MrGunn• 14 years ago

I'd love to see this study enrolled in the Reproducibility Initiative: http://reproducibilityinitiative.com

Strong claims require strong evidence.

snoldak924• 14 years ago

This is how the zombie outbreak starts...

patrickgzill2• 14 years ago

It is interesting to consider that periodic fasts and/or abstaining from certain foods for a time (such as Lent during the Orthodox calendar), seen in many religions, might have a health benefit by suppressing certain gut bacteria, or at least managing gut flora.

MichaelGG• 14 years ago

Is it actually interesting? Even the rules were chosen randomly, you'd expect any large body of rules to get something by sheer chance alone.

krenoten• 14 years ago

It might better be viewed as a behavioral "mutation" of sorts that improved the viability of those who adopted the practice. There are many interesting things that happen by chance.

AutoKorrect• 14 years ago

yes, it is interesting. Consider that vitamin C was known to prevent scurvy, but then that knowledge was lost, and rediscovered later on. How much knowledge may be codified in ancient customs, and that we might have forgotten the foundations for that knowledge.

justincormack• 14 years ago

American obesity is a recent thing that does not eg seem to be related to stopping fasts.

_stephan• 14 years ago

This an interesting article by the Economist about the human microbiome ("Looking at human beings as ecosystems"):

Link: http://www.economist.com/node/21560523

fernly2• 14 years ago

This is potentially huge news. If it can be replicated you can take all the high-fat/low-fat, high-carb/low-carb, paleo whatever diets and chuck them. "we show that one endotoxin-producing bacterium isolated from a morbidly obese human’s gut induced obesity and insulin resistance in germfree mice." "Germ-free mice" are mice raised from before birth with no germs, so the effect of a single infection can be observed without complications. They claim that a single bacterium strain from a human gut, infected into mice, gave them not just obesity but insulin resistance and inflammatory symptoms -- a close analog of the complex we call "metabolic syndrome" in obese people.

If even some cases of metabolic syndrome can be linked to a simple bacterium -- and cured simply by killing that bug -- this will have the economic and medicinal effects of, well, not the eradication of smallpox, but pretty close.

Scientifically it's the equal of marshal and warren finding the bacterial cause of peptic ulcers -- and they got the Nobel for medicine for that.

gte910h5• 14 years ago

>well, not the eradication of smallpox, but pretty close.

Heart disease kills far more people than smallpox ever did. You have a 20% higher chance of heart disease if overweight.

Pathogen from gut of obese human causes obesity in germfree mice

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