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by wdwvt1 1499 days ago
Microbiome researcher here. Like many microbiome results - this paper has tantalizing evidence of a powerful and systemic effect, but extremely limited direct evidence. The primary experiment in the paper is the transfer of stool contents from old mice to young mice (and vice versa). The chemical complexity of stool is hard to overstate - it's one of the most chemically diverse environments known. While the microbes are ~75% of the weight of feces (and thus of the fecal transplant) there is a huge complement of other things including host-derived effector molecules, fungal, and viral components. Three things that I think are important to think about:

1) A critical experiment to determine that it is bacteria (or fungal/virus) per se and not a host effector would be the transfer of contents from aged germ-free control mice (mice without microbes of any type). The authors mention a transfer protocol that could be optimized for fungal commensals, but don't address the more important germ-free control.

2) It is hard to characterize individual immune metabolites/signals (e.g. IL-10, IL-6, etc.) as either good or bad. The context determines the effect and they show changes in at least 20 cytokines in Fig 3E. While they focus on IL-6 and TNF, it's not immediately clear those are necessarily a part of pathogenic inflammageing. LBP conversely, seems pretty hard to interpret as anything but evidence of barrier permeability and this result seems strong.

3) It's not clear how much of this effect would sustain over the long term. The amount of time between fecal transplant and mouse sacrifice/result generation was only 18 days. Experiments with such a short duration seem like they might capture an unrelated effect due to some other coincident factor.

Overall, a well done paper with a lot of interesting things, but also reasons to be very skeptical of the magnitude of this effect. As usual, I will end with: you can dramatically improve your microbiome health (whatever that term actually means) by eating a high fiber diet like most humans did for most of evolutionary time.

5 comments

As a parent of young children, I have had sustained exposure to a diverse medley of fecal specimens varying in color, odor, consistency, and texture. Is there a particular stripe I should be targeting for transplanting from my children’s into my own microbiome?
I know you mean well but boy did this come off as profoundly weird.
There comes a point as a parent where this kind of humor is very normal. :)
Environmental faecal matter is just another one of those things!
Humor? Seemed factual to me!
I don't think we're too far off from people selling children's fecal specimens. I bet Peter Thiel is already doing just that.
:) yes, quite disturbing!
No its not, people are just ignorant. You eat ton of shit.

CTO of Microsoft wrote 6 books on molecular gastronomy named Modernist Cousine [1]. There are lots of pages in first book about managing environmental fecal matter (hint: there is a LOT of it around you and in the food you eat).

[1]: https://www.wired.com/2011/02/ff-myhrvold/

The “fecal veneer”
lmao "you eat ton of shit"
Why would your children have a more diverse biome than your aged self?
Its not more diverse, its different.
I would slightly modify your suggestion for 1; it may be easier to gamma irradiate the fecal samples (or something) to kill all microflora instead. It won’t tell us whether the chemical effectors came from the host or the bugs but I would prefer comparing healthy mice than two separate classes of mice.

Another idea I’m curious about would be to preserve fecal samples from a young mouse and transplant back to their older selves to see if that also shows the same effect.

It may not kill everything, eg. this one is known to be highly tolerant to irradiation:

https://en.m.wikipedia.org/wiki/Deinococcus_radiodurans

>you can dramatically improve your microbiome health (whatever that term actually means) by eating a high fiber diet

Is that (primarily) because high fiber food takes so long to digest that it gives more time for "stuff" to propagate in your gut?

No, its mostly because it can't be digested at all by humans but are food for bacteria as every cow knows. The benefit of slow digestion by fiber is mostly for diabetes control.

Fixing microflora (and hence influencing metagenome) however, is not that simple. You wont feed good bacteria only, but pathogenic too if you have them overpopulated, which will make things worst. You can't easily replace those with new ones coming from food because of the acid barrier. You might think that lowering it down is good idea, but its totally not, because you will soon find new neighbor h. pylory which can cause all kinds of shit, along with having less nutrientes available by stealing and unoptimal pH environment. Regular probiotics are usually meaningless (influencing environment like fart in the wind).

Eating carnivoir diet makes your acid stronger which further strenghtens your defences (only great if you don't have invaders).

Then, this is dynamic - good guys can become bad in specific context.

The best way to improve your microbiome health is to find FT surogate, some great probiotic like Visbiome or VSL3, eat fermented foods, use prebiotics, and obviously dont use antibiotics in relaxed manner (save them for emergencies, like once in decade, and even then help flora repopulation and good luck with fungi proliferation) and do not remove your apendix just for the sake of it.

Funny thing nobody mentiond antibiotics and how harmful they are. Yes, they can save your life but poping them every now and then borders to malpractice.

I am a software architect, not a doctor, but machine is a machine.

And yet, there is no evidence at all that people who take more antibiotics live shorter or worse quality lives...so does any of this really matter at all?
Absence of evidence is not evidence of absence. We have pretty strong data that suggests that antibiotic exposure is associated with negative health outcomes. For example, patients who had undergone antibiotic exposure within a 6 month period preceding their admission to the ICU had a 20% increase in mortality rate.

Another study [1] I just found showed that older women who had been exposed to antibiotics for => 2 months had increased risk of all-cause mortality and cardiovascular mortality (hazard ratio 1.49). Interestingly, if they had also been exposed to antibiotics in middle-adulthood, their mortality rate was even higher; which may suggest that antibiotic exposure permanently impairs the microbiome. Paper's conclusion: "Long-term use of antibiotics in late adulthood may be a risk factor for all-cause and cardiovascular mortality. The unfavorable effect of antibiotic exposure for subsequent risks of deaths due to chronic diseases needs to be considered."

[1]: https://pubmed.ncbi.nlm.nih.gov/31842690/

> For example, patients who had undergone antibiotic exposure within a 6 month period preceding their admission to the ICU had a 20% increase in mortality rate.

That seems like a very obvious case of correlation vs causation (people who need medicine are more likely to die than those who dont)

All I'm seeing from the two examples you gave are situations where sick people got sicker and died.

It's almost trite to say it at this point but correlation is not causation.

Kindly don’t say stuff like this. After taking antibiotics I had severe, severe anxiety that lasted months along with insomnia. Now the anxiety is mostly gone but I’m still dealing with some sleep issues. If you google antibiotics anxiety microbiome you can read a bunch of studies.
Sorry. Anecdotes are not useful or instructive here. No studies show a causal effect of antibiotics on anxiety. In fact, it wouldn't be surprising if people who needed medical treatment (causing an antibiotic Rx) later had anxiety due to the nature of their health condition.
There are quite a few studies done on mice where they show this.
It is somewhat rude to speak in imperative ("don't say stuff like this"), and it is completely non-informative. If you disagree with someone, stating your reasons is much more likely to change others' mind than speaking in imperative, which only makes you look like a bully ("don't say stuff like this or I'll take your lunch money").
I'd assume the person you are talking to is not a native speaker. I think Indians use language that might sound rude or passive aggressive.
The commenter prefixed with "kindly" which is about the same thing as saying "please". This makes it not imperative, but a request.
Kindly do not cite personal anecdotes as evidence.
Kindly do your own research instead producing spam answers.
You know where half of the worlds antibiotics go to? As growth promotion on animals. Growth promotion => obesity => metabolic syndrome => diabetes => shorter life (diabetes basically being accelerated aging disease)

Please, this should be primary school knowledge nowadays.

I was obviously referring to humans taking them, just as the person I responded to was. Please.
Humans eat animals. Humans are animals. Please.
Even relatively short term use of antibiotics can result in digestive issues lasting multiple years. Auto-brewery syndrome for example is linked to antibiotics and can seemingly persist until treatment by antifungals.
Of course. Yet still, there is no evidence that these people would live shorter or worse lives than if they hadn't taken the antibiotic. What if the infection they took the antibiotics for had caused more harm than auto-brewery syndrome? What if the unchecked infection caused problems that couldn't simply be solved by antifungals? My point was just that the person I responded to seemed to imply that antibiotics are very bad except in cases where they save your life, which is not really supported by current medical knowledge.
That’s assuming the antibiotics where needed, overprescribing them is extremely common even with viral infections. Peoples immune system can deal with the vast majority of bacterial infections, it just takes slightly longer than a trip to the doctor.

From a doctors perspective prescribing antibiotics encourages people to show up with minor illness, it’s bad medicine but good business practice.

Couple of comments replied mentioning studies in this area, and you dismiss them completely (i.e. you show no indication of any value assigned on points made). Seems like you have very strong beliefs/faith/stake in using antibiotics as tic toc.
That’s like saying “people who get cancer drugs die earlier”.
Who did you think you were replying to? I implied no such thing and the comparison to my comment doesn't even make sense.
> I am a software architect, not a doctor

Uh huh

> some great probiotic like Visbiome or VSL3

Sure are a lot of "you watered down the product" and false advertising lawsuits against these guys.

All pharmacies have lawsuits. Please stop and GTFO.
This seems like an overly hostile response to someone who expressed skepticism.
Saving antibiotics for once in a decade emergencies sounds nice until you find yourself getting painful recurring UTIs several times a year.
If you get UTIs serveral times a year, you should seriously rethink your life habits. By doing that you will temporarily fix one disease and pay the price having array of other.
Can visbiome or vsl3 be safely taken by just anyone? What are the risks?
Yes. Risks are basically next to 0, you can get bloated eventually or something trivial like that.

This should have been one of the mandatory COVID prevention methods.

I take visbiome and I’m just anyone. Not every day, though. It’s expensive and not needed. Once per week is what I do but I’m no expert.
It depends on context. There is no 'once a week' method.
Work in the field myself. The real answer is definitely we don’t know, but for whatever reason a high diversity (lots of different kinds of bacteria) seems to be almost universally good. Fiber is the major carbohydrate source for our gut microbiome, and a fiber-rich and fiber-diverse diet seems to provide lots of niches for various bugs to grow.
I'm not an expert, but I would probably have guessed the opposite. Lots of fiber means nice, consistent bowel movements. I'm pretty sure it speeds up your digestive tract, if anything -- it doesn't take a long time to digest, it doesn't digest at all.
> eating a high fiber diet like most humans did for most of evolutionary time

Can supplementation be an effective substitute for fiber derived from real foods? If so, are there any particular kinds of supplements you'd recommend?

Yerba Prima Psyllium can not be beat. It takes a couple weeks to get used to it, and I don’t mean only your gut: it does not dissolve in water, so when you mix the powder in water, you end up drinking what has the consistency of sludge. There is no flavor.

Whatever psyllium you choose, be careful of lead content. https://www.consumerlab.com/reviews/psyllium-supplements/psy... has reviews and analysis of 8 products, including lead content.

I’ve been using this stuff almost daily for many years.

Yeah so that article requires payment. Apparently it recommends the brand Yerba Prima as top lead-free choice.
Correct (I subscribe to consumerlab.com)
Almost all psyllium is grown in India. They only banned leaded gas last year.
Wow. So many products with lead. Thanks for sharing that link. I hope it helps a few people. I know it's going to help me.
Personally, I've decided chia seeds are a good way to get more fiber. Also a good source of omega-3s. More calories than some other options, but I like the idea of whole foods. They have a decent mix of soluble/insoluble fiber.
Chia is not a good source of omega-3 because they are primarily ALA Omega-3:

“ALA, the most common omega-3 fat, is an essential fatty acid that is converted into EPA and DHA. However, this conversion process is inefficient in humans. On average, only 1–10% of ALA is converted into EPA and 0.5–5% into DHA”

https://www.healthline.com/nutrition/3-types-of-omega-3

Thanks, TIL.
Chia is still a great food anyway and I eat some almost every day! Good fiber. Just get your Omega 3 somewhere else.
Fiber is a scrub brush that keeps the inside of your digestive tract clean so it can function properly. Supplements won't really do the job.

It would be like trying different gasoline additives instead of taking your car to the car wash.

I see your problem. You’re not supposed to rub the fibre supplements on your skin. You eat them like other foods.
Are you already eating tons of fruits and veggies (10 servings/day) and a good amount of whole grains? If not, I think that's where to start, rather than jumping into supplementation. IANAD
This is going to sound crass but I am willing to be the sacrifical lamb to my own (and others) potential benefit: can my wife poop in my butt and can I poop in hers to gain some benefit?

Along these lines, are there any potential health benefits to penis in butt sex? Or does the poop need to enter my butt?

I am legitimately asking a question in complete seriousness and I would like to know the answers. The subject itself is crass because it has to do with our excrement and sex. Please don't push this out of visibility because you find the subject (or the direct language I use) distasteful. Thank you.