Sterilizing The Gut With Antibiotics Reverses Obesity

Philomath

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From a study in the Nature Today journal:

University of Geneva researchers reported that animals without intestinal microbiota had better glucose tolerance and insulin sensitivity, less white fat and lower body mass.

Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity1. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning2, 3, 4. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

Peat's right again!

(http://www.nature.com/nm/journal/vaop/n ... .3994.html),

This story was originally found on The Scientist Magazine website:
http://mobile.the-scientist.com/article ... ps-obesity
 

haidut

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[moderator edit: topics merged]

Big thank you to user Philomath who has posted this in another thread but nobody seems to have noticed it so far. So, Charlie and the mods - when we find the other thread maybe we can merge the two.
Bottom line of this study - Ray Peat right once again that having a sterile gut, while impractical, is a great way to increase metabolism and improve a number of health parameters including fat stores and overall weight. The benefits are quite likely due to the reduction in peripheral serotonin production, given that serotonin has definitively been shown to be a causative factor in obesity. In fact, a few Big Pharma companies are feverishly trying new inhibitor of serotonin synthesis as potential treatment for obesity. I think Roche's work is the the most advanced in the sense that it is the closest to being tried in humans (probably in 2016). As a confirmation of the improved metabolism in the sterile gut mice, if you look at Figure 2(g) you will see that their oxygen consumption doubled, similar to the levels observed with treatment by the drug DNP (another study).
The gut sterilizing protocol was the same as the one used in the study I posted earlier this year on the gut-serotonin connection, so the doses are not that high and probably practical to try in humans.

http://www.nature.com/nm/journal/vaop/n ... .3994.html
http://mobile.the-scientist.com/article ... ps-obesity

"...The gut microbiome is typically considered essential for proper health, but a study in mice shows that, at least when it comes to insulin sensitivity and obesity, that may not be the case. In Nature Medicine today (November 16), researchers reported that animals without intestinal microbiota had better glucose tolerance and insulin sensitivity, less white fat, and lower body mass. “Although treating obesity with high doses of antibiotics is unrealistic—mainly due to the risk of antibiotic resistance—we want to explore alternative ways of suppressing or modifying the microbiota, and to identify the exact bacterial genes responsible for this phenomenon,” Mirko Trajkovski of the University of Geneva said in a statement. “We would then target only those, without having to deplete the entire microbiota.”
 

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Nicholas

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haidut said:
post 112393 Ray Peat right once again that having a sterile gut, while impractical, is a great way to increase metabolism and improve a number of health parameters including fat stores and overall weight. The benefits are quite likely due to the reduction in peripheral serotonin production, given that serotonin has definitively been shown to be a causative factor in obesity.

and yet, i doubt the absence of a microbiota is the only event of having low serotonin. I couldn't tell, but does this study show how long the mice were on antibiotics, what type of antibiotics, and how long data was taken on the mice?

haidut said:
post 112393 we want to explore alternative ways of suppressing or modifying the microbiota, and to identify the exact bacterial genes responsible for this phenomenon,” Mirko Trajkovski of the University of Geneva said in a statement. “We would then target only those, without having to deplete the entire microbiota.”

this is probably the most interesting quote because it points to the potential that the benefit is not in a sterile gut (as we all admit is impractical), but in the depletion of specific bacteria.

another factor to consider is that we do not know that the effects have anything to do with serotonin, as you say it's a "likely"....but if serotonin were the only factor, these mice would have to benefit from a therapy which lowered serotonin and nothing else. Do we know that the bacteria themselves have an effect beyond serotonin?
 
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tara

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Nicholas said:
post 112395 Do we know that the bacteria themselves have an effect beyond serotonin?
They do if enough endotoxin gets through the gut barrier - endotoxin is a burden on liver and other systems.
 
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Nicholas

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tara said:
post 112403
Nicholas said:
post 112395 Do we know that the bacteria themselves have an effect beyond serotonin?
They do if enough endotoxin gets through the gut barrier - endotoxin is a burden on liver and other systems.

good point. so endotoxin can have a detrimental effect beyond serotonin.
 
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XPlus

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This is what they describe as emotional eating.
Because serotonin is the feel good hormone.
 

Nicholas

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XPlus said:
post 112408 That's why they ascribe it to emotional eating.
Because serotonin is the feel good hormone.

do we have a scientific representation of what serotonin feels like?
 
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haidut

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Nicholas said:
post 112409
XPlus said:
post 112408 That's why they ascribe it to emotional eating.
Because serotonin is the feel good hormone.

do we have a scientific representation of what serotonin feels like?

Tired, spent, exhausted. The central fatigue hypothesis says after a long endurance event or prolonged stress the elevation of CNS serotonin is what makes people feel like that. If it becomes high enough, fever and trembling and confusion set in. When it is as high as in carcinoid syndrome psychosis and esxtremely aggressive behavior set in as well.
 
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haidut

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Nicholas said:
post 112395
haidut said:
post 112393 Ray Peat right once again that having a sterile gut, while impractical, is a great way to increase metabolism and improve a number of health parameters including fat stores and overall weight. The benefits are quite likely due to the reduction in peripheral serotonin production, given that serotonin has definitively been shown to be a causative factor in obesity.

and yet, i doubt the absence of a microbiota is the only event of having low serotonin. I couldn't tell, but does this study show how long the mice were on antibiotics, what type of antibiotics, and how long data was taken on the mice?

haidut said:
post 112393 we want to explore alternative ways of suppressing or modifying the microbiota, and to identify the exact bacterial genes responsible for this phenomenon,” Mirko Trajkovski of the University of Geneva said in a statement. “We would then target only those, without having to deplete the entire microbiota.”

this is probably the most interesting quote because it points to the potential that the benefit is not in a sterile gut (as we all admit is impractical), but in the depletion of specific bacteria.

another factor to consider is that we do not know that the effects have anything to do with serotonin, as you say it's a "likely"....but if serotonin were the only factor, these mice would have to benefit from a therapy which lowered serotonin and nothing else. Do we know that the bacteria themselves have an effect beyond serotonin?

I think some of the scientists that did this study also participated in the gut-serotonin study since they refer to it and also used the same protocol for sterilizing the but - i.e. 40 days on a combination of at least 6 antibiotics including Amoxicillin, gentamycin, Neomycin, etc. I have attached the full study to the original post if you want to look more into it.
As far as lower serotonin being the main beneficial effect - as I mentioned the study did not make that conclusion but I explained why it is virtually guaranteed to be involved. Inhibiting peripheral serotonin synthesis had been definitely shown to reverse obesity, insulin resistance, and even diabetes II. As per the gut-serotonin study and a few other I referenced in that post, over 90% of the serotonin is produced in the gut by the interaction of bacteria with the chromatin cells. Killing that bacteria as the study showed resulted in 90% reduction of peripheral serotonin. Another, related study using the same gut sterilizing protocol found that killing all gut bacteria resulted in 20%-30% weight loss in rats. In all the studies with gut sterilizing, oxygen consumption and resting metabolism almost doubled. So, while the connection is not definitive I think there are very few likely factors other than serotonin that may be contributing to such dramatic increase in metabolism and weight loss. Remember, serotonin is the primary signal for slowing metabolism, in hibernating animals and humans alike. Serotonin antagonists raise bears out of slumber much to their chagrin.
Dopamine agonists, which also inhibit both central and peripheral serotonin synthesis by inhibiting TPH1 and TPH2, also result in fat loss and increase in oxygen consumption. I posted a few studies on cabergoline and lisuride showing 6kg fat loss in just a few weeks. So, everything seems pretty consistent to me. Maybe I am not accounting for the diminished endotoxin but one of the main mechanisms of endotoxin damage is increase in NO/serotonin production, so that seems to go back to the main culprit 5-HT.
Just my 2c.
 
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XPlus

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Nicholas said:
post 112409
XPlus said:
post 112408 That's why they ascribe it to emotional eating.
Because serotonin is the feel good hormone.

do we have a scientific representation of what serotonin feels like?

"Science" doesn't seem to agree on what serotonin exactly is, in theory.
I doubt it's close enough to settle on how it precisely feels in reality.
Still, I don't see the serotonin feeling to possibly be independent from what it's usually associated with: fatigue, excess estrogen, digestive irritability, mood swings, fear and aggression, etc.
 
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XPlus

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haidut said:
I posted a few studies on cabergoline and lisuride showing 6g fat loss in just a few weeks.

Is that 6 gm or kg?
 

brandonk

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haidut said:
post 112393 Big thank you to user Philomath who has posted this in another thread but nobody seems to have noticed it so far. So, Charlie and the mods - when we find the other thread maybe we can merge the two.
Bottom line of this study - Ray Peat right once again that having a sterile gut, while impractical, is a great way to increase metabolism and improve a number of health parameters including fat stores and overall weight. The benefits are quite likely due to the reduction in peripheral serotonin production, given that serotonin has definitively been shown to be a causative factor in obesity. In fact, a few Big Pharma companies are feverishly trying new inhibitor of serotonin synthesis as potential treatment for obesity. I think Roche's work is the the most advanced in the sense that it is the closest to being tried in humans (probably in 2016). As a confirmation of the improved metabolism in the sterile gut mice, if you look at Figure 2(g) you will see that their oxygen consumption doubled, similar to the levels observed with treatment by the drug DNP (another study).
The gut sterilizing protocol was the same as the one used in the study I posted earlier this year on the gut-serotonin connection, so the doses are not that high and probably practical to try in humans.
Here is the earlier post with information about this topic:
https://www.raypeatforum.com/forum/view ... nin#p77024

In practice, unless you use antibiotics and risk toxic overload, I find it is quite arduous but not impossible to keep a germ-free gut, if I can somehow keep to a highly restrictive diet of no starch, and only a little seafood or liver, egg and a little eggshell. Small amounts of soft cheese without the whey are also ok.

Collagen, coconut oil, strong coffee, and fruit juice (no pulp) are all fine for me as staple food.

I can tell it's working. There is no odor of putrefaction in undigested food that passes through in small amounts, several times a day. I also noticed, as the study suggests, a rapidly reduced bodyfat percentage around the waist.

I wouldn't recommend this to anyone else, since it is quite arduous, and untested, and therefore potentially even dangerous.
 
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Nicholas

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haidut said:
post 112410
Nicholas said:
post 112409
XPlus said:
post 112408 That's why they ascribe it to emotional eating.
Because serotonin is the feel good hormone.

do we have a scientific representation of what serotonin feels like?

Tired, spent, exhausted. The central fatigue hypothesis says after a long endurance event or prolonged stress the elevation of CNS serotonin is what makes people feel like that. If it becomes high enough, fever and trembling and confusion set in. When it is as high as in carcinoid syndrome psychosis and esxtremely aggressive behavior set in as well.

i'm only trying to be as scientifically-minded and inquisitive as you are when i ask: so the only scientific representation of serotonin that we have is in relation to endurance events and prolonged stress? that these events raise serotonin and make someone, "tired, spent, exhausted"? my question is also rhetorical in that it doesn't seem serotonin is really understood completely according to the science. xplus puts science in quotation marks, but why? is not the science admittedly confused and admittedly knowing that serotonin is complex?
 
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Tarmander

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Very interesting.

I will add this about the feeling of serotonin. I believe there is also a satisfactory numbing that goes along with it. I think this is partially why this can be so confusing, and makes it hard to identify exactly what you might be feeling. From my own experience, serotonin, when I am pretty sure I am experiencing it, feels like a restlessness, combined with numbness, satisfaction, and a foggy haziness. You don't feel good laying down, you don't feel good moving, yet doing either does have some type of satisfied feeling with it.

Edit: here are symptoms of serotonin syndrome. I would guess most of these you could use if they occur in conjunction, but just less severe then SS

Agitation or restlessness
Confusion
Rapid heart rate and high blood pressure
Dilated pupils
Loss of muscle coordination or twitching muscles
Muscle rigidity
Heavy sweating
Diarrhea
Headache
Shivering
Goose bumps
 

Wilfrid

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My comment is not directly related to obesity but when I read this post it reminds me that the only time I went into remission ( for almost 3 years ) of the crohn's it was when I got IV injection of 3 antibiotics.
Yet, in a very near future, the most promising non-invasive treatment for people with IBD ( ie people with probably very high serotonin related disease ) is indeed intestinal bacteria.
http://gut.bmj.com/content/early/2015/0 ... 9.abstract
 

Wilfrid

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And interestingly enough, one of the most potent and therapeutic by-product of this F.Prau intestinal bacteria species is....salicylic acid!!
 

haidut

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XPlus said:
post 112415
haidut said:
I posted a few studies on cabergoline and lisuride showing 6g fat loss in just a few weeks.

Is that 6 gm or kg?

It's 6kg, sorry about the typo. I corrected it.
 
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haidut

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Wilfrid said:
post 112435 My comment is not directly related to obesity but when I read this post it reminds me that the only time I went into remission ( for almost 3 years ) of the crohn's it was when I got IV injection of 3 antibiotics.
Yet, in a very near future, the most promising non-invasive treatment for people with IBD ( ie people with probably very high serotonin related disease ) is indeed intestinal bacteria.
http://gut.bmj.com/content/early/2015/0 ... 9.abstract

You do know about the recently confirmed hypothesis that Chron's is caused by a bacteria, right?
https://en.wikipedia.org/wiki/Mycobacte ... berculosis
"...Mycobacterium avium subspecies paratuberculosis (MAP) is an obligate pathogenic bacterium in the genus Mycobacterium.[1] It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps the human disease Crohn's disease."

If that is true, then no wonder the IV antibiotics put you in remission.
 
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XPlus

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haidut said:
post 112443
Wilfrid said:
post 112435 My comment is not directly related to obesity but when I read this post it reminds me that the only time I went into remission ( for almost 3 years ) of the crohn's it was when I got IV injection of 3 antibiotics.
Yet, in a very near future, the most promising non-invasive treatment for people with IBD ( ie people with probably very high serotonin related disease ) is indeed intestinal bacteria.
http://gut.bmj.com/content/early/2015/0 ... 9.abstract

You do know about the recently confirmed hypothesis that Chron's is caused by a bacteria, right?
https://en.wikipedia.org/wiki/Mycobacte ... berculosis
"...Mycobacterium avium subspecies paratuberculosis (MAP) is an obligate pathogenic bacterium in the genus Mycobacterium.[1] It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps the human disease Crohn's disease."

If that is true, then no wonder the IV antibiotics put you in remission.

I read a while ago that this requires an invasive therapy of a trio of antibiotics used for at least 2 years and only a handful of doctors actually believe in it and approve it.
The reason they use 3 is because they're unsure which one works and I think part of why it takes this long is that doctors don't account for hypothyroidism.
 
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haidut

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XPlus said:
post 112595 Mycobacterium avium subspecies paratuberculosis

Those were older studies with older antibiotics to which the bacteria may have been resistant. A newer study had much better results after just 3 months of treatment.
http://www.crohns.org/treatment/
"...A trial conducted by Shafran et al.New window link indicator in Orlando, Florida, treated 29 Crohn's disease patients with a combination of Rifabutin and Clarithromycin. After three months of treatment, the investigators found that 8 of the 29 patients were in clinical remission, 9 of the 29 patients experienced marked improvement, 8 of the 29 patients experienced minor improvement, and 4 of the 29 patients had to be taken off the medication, due to intolerance of side-effects."
 
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