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homeostasis3434 t1_j2okr3d wrote

Biggest pet peeve about microbiome studies is when they say the microbial community is the CAUSE of something.

These studies seem to ignore the very real possibility that diet itself alters the microbiome, so it stands to reason if you have a horrible diet, the makeup of your bodies microbial community will be altered from someone who has a more balanced diet.

It's no different than saying someone with a diet of red meat and potatoes will have a different microbiome than someone with a vegetarian diet. The altered microbiome in a vegetarian didn't cause that person to become a vegetarian, their lifestyle choices affected their microbiome.

There's also been studies that try and link c-sections to altered microbiomes, however they ignore the possibility that the underlying issue that forced a woman to have the c-section in the first place, was the cause of these changes in community makeup.

There's just so much emphasis on the causal link between microbiome and human health that I think these researchers really need to take a step back and think about what they're saying for a minute. I don't know how some of these statements get published in the first place.

End rant.

Edit: to be fair, the study doesn't seem to make the claim the title of the post does. The study just says there are changes in the gut microbiome of people with varying degrees of obesity. The title of this post claims the microbiome affects obesity. These are not the same thing.


Ituzzip t1_j2ovk5n wrote

The studies are literally being done to accumulate data to be able to test this logic.

You have your logic in that you suspect diet is the primary causative factor, and changes in microbiome follow, and it’s perfectly reasonable logic.

But it’s also possible that the microbiome affects things like hormone levels, creates fermentation byproducts like lactic acid and acetic acid that change blood sugar profiles and the speed of digestion, it’s possible the microbiome affects appetite, and different microbes could cause people to tend to eat less without conscious thought about it.

Or a sudden change in microbiome could induce metabolic changes quickly, which would eventually revert to baseline without behavior changes, but remain robust if people keep supplying the different microbes.

Or there could be a combination of multiple factors and inputs that are more complex than anyone has thought of so far.

Logic can make perfect sense and still turn out to be wrong—that’s why the studies are being conducted.

Even if diet comes first and microbial changes follow, studying the microbiome could someday identify a causative link between obesity and things like gastrointestinal cancers.

It will take many studies and a large accumulation of data before people are able to draw any conclusions or even figure out what the more important kinds of tests are.


SaltZookeepergame691 t1_j2p2aez wrote

There are number of trials looking at microbiota interventions and obesity, and none have found any effect.

It may be that we aren’t using the right protocol, but it really does seem that if there is an effect it is far smaller than previously believed.

Latest trial to my knowledge is this one:

Others include but are not limited to:

Even the animal models that launched this research are overhyped, finding marginal effects in tiny experiments often with improper controls or analysis approaches.


Ituzzip t1_j2p4ysz wrote

I suspect that scientific research interest and funding has been too fixated on obesity itself as a catch-all target for all the health issues associated with obesity.

There might be more value in understanding why all these conditions are connected to obesity, and whether microbes play a role in them.

But that’s just conjecture on my part. Given the complexity of this phenomena and our very limited current understanding of the microbiome, we have not come close to exhausting all the options.

But again, we won’t know what questions to ask until we get a wider base of information to use to find patterns.


SaltZookeepergame691 t1_j2qxy40 wrote

I think the take home here from the above trials is that the hype far, far exceeded the evidence - if microbiota modulation for obesity was a drug requiring substantial financial investment, it very likely would have been dropped in preclinical development, and it certainly would have been dropped after these negative pilot trials. By contrast, the effect of, say FMT on single and multiple recurring C diff is very obvious, and the RCT evidence for an effect in ulcerative colitis is at least mixed, if not somewhat promising.

The reason for the focus on obesity, rather than say obesity-associated CVD or CKD or NAFLD or extra-GI cancers, is that these conditions take years to develop, in a relatively small number of people - it should be much easier to see an effect on weight in people already obese, if one exists. There is some very limited evidence that microbiota intervention can improve glucose homeostasis in people, but I wouldn’t hang my hat on those studies.


MrTickle t1_j2pyyfu wrote

The only person claiming causation is OP. The underlying paper talks in correlations only.


SaltZookeepergame691 t1_j2rus63 wrote

The actual study acknowledges they only have correlative data and then loses restraint and talks about causation in the Conclusions...:

>Members of genera Eubacterium coprostanoligenes, Lachnospiraceae NK4A136, Akkermansia, and Parabacteroides might be potential taxa for intervening in obesity regarding different degrees of obesity. Furthermore, three species, Prevotella copri, Bacteroides ovatus, and Dorea formicigenerans also showed great potential to regulate obesity. In contrast, a strategy that targets the inhibition of certain taxa in different obesity groups might be another way to improve obesity.


RuggerJibberJabber t1_j2t4m34 wrote

"might" and "potential" are key words you're glossing over. One of the main points of having a conclusion section is to give some opinion and suggest further studies that future researchers on the topic could examine.


messopotatoesmia t1_j2ps3il wrote

You're ignoring the colony factor; bad microbes rarely show up in isolation, and it's the synergistic effects between them that causes the biggest side effects.

You're also ignoring external factors which alter the microbiome and cause obesity - like, for example, dishwasher rinse aids, glyphosate (which messes with shikimate pathways in akkermansia muciniphila bacteria), red 50 dye (which messes with gut permeability) and so on.

Diet isn't the only causative agent.


SaltZookeepergame691 t1_j2os9wk wrote


No human interventional studies have found any effect of changing the microbiota on obesity, and there have been a good number, and any non randomised cross sectional studies are far too at risk of reverse causation and confounding to say anything on causation.


Rhawk187 t1_j2p4a7s wrote

Yeah, I don't suspect it "causes" obesity, but I feel like it may make it harder to reverse.


hodler41c t1_j2p6lyx wrote

I was just gonna say, chicken or the egg? But you explained it better.


SandyBouattick t1_j2p653c wrote

If sensational claims of correlation equating to causation were banned here, there would be far fewer posts.


lookmeat t1_j2q0w0n wrote

Or it could be both, there's a lot of feedback loops on the digestive system. Or it could be that both things are mostly unrelated, but there's a common issue which causes both unrelated (e.j. high processed sugar which make consumers crave more, separately also promotes monoculture on the guy biome).

Thing is there's very little papers identifying casual effects, only correlations. That's why there isn't an official medical advise, but just recommendations from people on the field (as in going this can't hurt). If the scientific community actually believed there was an issue proven to be caused by gut biome, we'd read papers on how to tweak probiotic cocktails and what not to prevent this.


YooperScooper3000 t1_j2pf6a7 wrote

C-sections? Many of them are due to position of the baby. A breach baby is not coming out without surgical intervention and has nothing to do with gut micro biome.


howthefocaccia t1_j2pixd0 wrote

We do vaginal breech birth where I work….


YooperScooper3000 t1_j2plxno wrote

That’s good to know. Unfortunately, one of my friends had a baby with its head in the wrong position and she was given a c-section. And another had a breach baby that was given a c-section. I guess it depends upon how the baby is doing? Maybe some doctors don’t have the patience?


howthefocaccia t1_j2povbw wrote

‘Your biggest risk factor for Caesarean section, is the hospital you choose for your care’ - Dr Neel Shah, Harvard Medical.


Banana_Skirt t1_j2rdy1l wrote

It's also a cycle in a way. The more doctors do c-sections for breach births then the less experience they have with doing vaginal breach births. At a certain point, you don't want a doctor with no to little experience trying to do it.


Zestfullyclean87 t1_j2q7abm wrote

And in some places, that’s illegal to knowingly facilitate a breech birth in that way


nato2271 t1_j2qqepw wrote

I came here to rant about the same thing..thanks for saving me the time


atsugnam t1_j2qdjjn wrote

The interesting part of this is targets to study - what happens if we wipe out some of these species from the biome, does the persons hunger drive change, do they lose weight?

These biome changes likely do occur based on diet change, but does another diet change revers these changes back down the line toward normal biome?

The biome changes appear to be a symptom, but are they also a contributor to future obesity - by changing the gut function or by changing behaviour?


Papkiller t1_j2qmzi2 wrote

Same. The classical correlation and causation argument. I mean you'd think people who do studies had an intro class into statistics right.


Fairuse t1_j2rc39f wrote

Study find people with obesity have excess fat. I guess excess fat causes obesity. Blame the excess fat. I can’t help my obesity problem because this excess fat is preventing me from not being obese. If it wasn’t for the excess fat then people wouldn’t be obese…


Kickstand8604 t1_j2s9w1q wrote

I guess the question is now, what caused obesity 1st, the diet or the microbiome. I think a good experiment to run would be, to look at weight gains before and after taking a round of antibiotics. If the antibiotics reduce the amount of gut flora, then there should be some type of weight gain.


rydan t1_j2pzybl wrote

Eat poop from a skinny person and see if you lose weight. Seems like an easy test to perform.


Zestfullyclean87 t1_j2pdl5f wrote

This is exactly how I feel about it.

The reason why people gain weight, is because they are in a calorie surplus.

And another thing I see is, “they just eat too much sugar” or “too many carbs.” And yeah that may be the case for many people, but I also think it’s disingenuous - because people are overeating everything. not JUST sugar. People don’t just eat too much processed foods… they eat too much whole foods too.

But when we try to act like microbiome is the cause of obesity, or hormones are the cause of obesity, this and that, it really pisses me off because I don’t understand how people can look at the way we eat, and think it’s something else causing obesity.


messopotatoesmia t1_j2pswwk wrote

Why do they eat too much?

You'd think that with all of our other homeostasis mechanisms, this one wouldn't fall apart quite so easily.

So why? And "because we used to starve" is not a valid answer.


Zestfullyclean87 t1_j2pylci wrote

I’m not sure what direction you’re trying to take your question, or why you are assuming I would answer a certain way.

As to why people overeat. Over the past 1-2 generations, we had people being raised on “clean plate club” mentality, or scarcity mentality.

We also have a new phenomenon, which j feel like is not talked about enough: variety of foods. We did not have taco Tuesday, sushi happy hour Wednesday in the 1950’s. People were more likely to eat the same 4-5 meals

There are loads of reasons, there were many cultural shifts in the way we eat that happened gradually over the last 50 or so years.

Then you have people who eat a lot of food because they’re simply not calorie aware. I think this is the issue with most people in western society - they’re just not aware.


Ituzzip t1_j2qeanb wrote

How can you so easily say you know the answers to these questions when it is one of the most controversial unknowns in science? Especially when your analysis seems to focus on the U.S. while obesity levels are creeping up as a global phenomenon.


Zestfullyclean87 t1_j2qja8i wrote

It’s physics. What’s controversial about physics?

It’s not a coincidence that the same parts of the world with an insane level of choice when it comes to food, happen to be the most obese countries in the world.


messopotatoesmia t1_j2pz9j5 wrote

If you raised children deliberately without that mentality, and they start putting on weight, you'd see that this isn't a great reason either.

And as for calorie aware, our bodies have homeostasis mechanisms for everything else. So why does this fail?


Zestfullyclean87 t1_j2pzlwb wrote

It “fails” because we don’t defy the laws of physics. Energy cannot be created nor destroyed. If you take in more energy than you expend, it’s not just gonna go away, it’s gonna be stored, in this case, as fat


messopotatoesmia t1_j2q19ho wrote

Why don't we just stop eating when we have enough? We're wired with chemical sensors all over the place to determine the content of our food. Some foods are also immediately satiating - for example, chicken bone broth.

There's a missing puzzle piece here, which is why they call it an obesity epidemic - it behaves like a disease, and no-one understands the root cause yet.

We also don't normally extract anywhere near the total energy from our food that it contains, so comparisons with a bomb calorimeter aren't accurate. Microbiome diversity determines whether or not - for example - you break down cellulose in your colon. If you've got methanogenic bacteria in your gut, you're going to put on weight when someone else without them might not.


Zestfullyclean87 t1_j2q6v3k wrote

Well you seem to think that, if a food is satiating, then we robotically stop eating. That’s not the case.

As for why we don’t stop eating when we have enough… you’re forgetting that a lot of people are being raised on very large portions. When you’ve eaten that way your whole life, you’ve pretty much trained yourself to not be satiated until you’ve already had too much. Chicken stock does not make you stop


messopotatoesmia t1_j2qec1n wrote

That's pretty much the definition of satiating. It sates the urge.

I grew up in another country. Got much fatter once I was here. And chicken bone broth makes me rapidly satiated; even foods cooked in it. I eat it, my hunger gives way rapidly to feeling annoyingly full in about 1/4 the quantity it would normally take. My theory is that it's rich in L-Glutamine, calcium and magnesium, and that's enough to trip the mechanism and to provide enough raw precursors for the gut lumen to generate GLP-1 in large quantities, a bit like semaglutide, but that's just a hunch.


Zestfullyclean87 t1_j2qj6yx wrote

So you think being satiated forces a person to put the food down?


messopotatoesmia t1_j2qqv52 wrote

Unless they have a busted ventromedial nucleus of the hypothalamus, yes.

If that's shot, they'll eat until they burst, but that's very unlikely - though the cause might be glutamate toxicity.

It might happen with people with poor gut barrier function if they consume a lot of wheat; wheat-germ agglutinin (WGA) binds leptin receptors, blocking them. Leptin inhibits hunger. Similarly, WGA also binds insulin receptors, so it's a bit of a double whammy; it takes the brakes off hunger and increases blood glucose, causing it to be more likely to be stored as fat. Regardless, hunger increases.

You seem to be quibbling over the definition of satiety. Satiety means "feels full/done with food". By definition, if someone experience satiety, their hunger is sated, and stops.


hippogrifffart t1_j2q3egu wrote

What do you mean our bodies have homeostasis mechanisms for everything else?


atsugnam t1_j2q6yiv wrote

Most of the states of chemistry in your body are pretty tightly regulated, mostly because you die fairly quickly if they get too far off of very narrow margins. Eg electrolytes, water, temperature, acidity. It appears that our food systems aren’t so tightly controlled for most people. That at a population level this is significant and growing is indicative of influence beyond people choosing it.

Edit to add: this isn’t necessarily an unexpected thing - humans succeeded through developing a very wide dietary compatibility, meaning this variability that is good enough to reach reproduction age would appear to be the selected evolution. The problem is now we want longer healthier lives way beyond what evolution would bother with, this study seems to show that the gut biome varies predictably with obesity, says nothing of causation, but does identify potential study targets eg, does this variance then make hunger change, reinforcing obesity maintaining behaviour etc.


Zestfullyclean87 t1_j2qvyow wrote

You don’t do that with calories because your brain doesn’t say “wait a minute, I ate too many calories. Let’s burn those calories to balance it out!”


atsugnam t1_j2r81wh wrote

But some people stop eating at the right amount of calories for their demands. Why is that possible for some and not others.

Also there is evidence for people increasing their activity levels when they eat more calories, not going out and exercising, but their average activity level increases.

The reality is we don’t know. There are some fundamentals, but they aren’t well understood: if you had no gut biome, you would have to eat 3 times the calories you do now to maintain your current weight. The biome has a huge impact on the way and amount of calories Welch individual can extract from food, and as of now, we don’t have a realistic method to measure it, and no understanding of what a biome change makes to the calorie absorption rate of any individual.

That’s why literally any absolute statement or claim is not useful, or accurate. In either direction.


Zestfullyclean87 t1_j2rcjg9 wrote

If you’re eating at the right calories for your body’s demands, then you are maintaining your weight

And if there’s evidence that eating more leads to an increased activity level, that does not change the fact that if they are overweight, it’s because they’re eating more calories than they should

> The reality is we don’t know.

We do know. This is science denial, what you’re doing. Not unlike claiming the earth might not be around

Edit - also you’re saying that the gut biome has a huge impact on how we burn calories, then in the same sentence you say we don’t know have reliable data on it. Those two statements are incompatible with each other. We can’t say definitively “x has an impact on y” without a reliable way of measuring it


atsugnam t1_j2rnqlu wrote

I’m not denying science, there’s a lot to learn, but we already know that lean individuals absorb fewer calories from their intake than obese ones.

This means an obese persons calories in ~ calories out equation is different and prejudicial to maintaining obesity.

And that’s just one scratch on the surface of an ultimately meaningless reduction of a vastly complex system, once you start to gain weight, it gets harder and harder to lose it.


Zestfullyclean87 t1_j2rsuot wrote

But you are denying science. You’re basically saying “we don’t know, but I know.”

We know an obese person’s calories in and calories out is different to maintain their body size - that’s because it takes more energy to maintain mass, and they have a higher calorie need. What this means is that once they reduce their intake, they have an easier time losing weight.

This is not any different than what I’m saying, you’re just misinterpreting it as something else

It isn’t that lean people “absorb” fewer calories, it’s that they maintain their size on fewer calories, since they have less mass. It seems that you’re choosing to interpret this as “lean people can eat the same number of calories as obese people, they just don’t absorb it” which is not what’s happening.

If you downsized from a 4500 square foot house, to a 500 square foot apartment, your energy bill would lower. The exact same thing happens in the human body. The larger you are, the more calories you need to maintain your size, sort of like how it takes more energy to cool down a large house


atsugnam t1_j2rymx9 wrote

You didn’t read the study I posted, or what I said.

Obese people absorb more calories from a given amount of food than a lean person given the same amount. We know this because fewer calories are excreted in their waste. So we know that obese people extract more calories from the same input calories than lean people do.

I didn’t claim I knew it, I referred to a study proving it.

But you are too fixated on your worldview to actually read and understand what the evidence shows over what you think you know. You’re falling for your own personal biases all while claiming that’s what I’m doing.


Zestfullyclean87 t1_j2s08br wrote

No, I read what you said, but the problem is, you’re misinterpreting how calorie needs work.

It isn’t the smaller person doesn’t absorb the calories. It’s that they have a lower calorie need, to maintain their size.

If a smaller person is eating the same number of calories as an obese person (assuming that other factors such as height, sex, and age, and activity levels are the same) then you would have to explain by what mechanism the lean person isn’t storing energy.

Because energy that’s inputted, but not used, doesn’t just disappear. This is where your scientific understanding is falling short - energy cannot be created or destroyed, it can only be transferred. and if it’s not transferred in the body by way of activity, it has to be stored as fat. Fat is stored energy.

So no… lean people and obese people do not consume the same calorie amounts. Not unless the lean person is extremely active, but activity is a lot less relevant in determining one’s size, than caloric intake


Zout t1_j2t398g wrote

You might have read what he said, but it seems to me you didn't process it. He literally says that obese people excrete less calories, so this is the mechanism you're asking for. Leaner people don't get all the energy out of the food and into the body.


atsugnam t1_j2txp6d wrote

Ok, again, go and read the study.

They measured the calories dumped in the fecal waste excreted following a fixed calorie intake.

Lean people dumped more calories out per calorie in, their gut didn’t absorb as much of the intake as an obese person did. For the same given intake of calories.

This isn’t about maintaining mass, this is about physically absorbing more of the energy in a given parcel of food.

You’re so fixated on how you think the human body works you aren’t even reading what is in the study.

To couch it in your own words - it’s physics: why is it when a lean person eats a given calorie input do they excrete more calories out in there faeces than an obese person for the same input. How does a lean person get the same calorie absorption when more of the energy went into the toilet?