Human microbiome myths and misconceptions | Hacker News Reader

Human microbiome myths and misconceptions

nature.com

217 pointslxm90 comments

Pseudoscience involving human microbiome seems to be very popular here in HN. Whatever health articles gets posted, someone starts touting their favourite internet theory on how it is all completely determined by the human microbiome, using getting a lot of upvotes. I would advice those people to carefully read the caption on Figure 2 in the article:

> Changes in faecal microbiota have been associated with a range of diseases in humans. Interestingly, despite the diverse nature of these conditions, and the organs they affect, there are some broadly common recurring microbiota features, such as reduced diversity and increases in facultative anaerobes like Enterobacteriaceae. One common theme amongst these conditions is that they often result in increased levels of inflammation, at local and systemic levels. Such inflammation can, in turn, deplete the gut microbiota (and consequently microbial gene diversity), and allow facultative anaerobes such as Enterobacteriaceae to proliferate. This directly impacts the metabolic output of the microbiota, and its interactions with the host. Additionally, there are other host factors that contribute to disease and gut microbiota composition, such as age, BMI and medication, as well as host metabolism and immune response. This makes it very difficult to distinguish cause from effect in correlation-based studies.

In short: it is all much more complicated than you think and separating the cause and effect is something no-one has managed to do convincingly yet. It's possible that the microbiome health really is as important as some people think, but it's also possible that the role is more minor and the changes in it associated with various diseases is just incidental.

The whole point is that we are constantly finding causal, not casual relationships with our microbiome.

Just last week there were two significant discoveries:

For what is being found in long Covid for example, a promising hypothesis is viral persistence in the gut causing major dysbiosis and leading to lower production of serotonin. And we even saw the transfer of Alzheimer’s symptoms from an old host to a young one.

I think it just shows how important microbes are in our lives and what a strong influence they have.

https://www.pennmedicine.org/news/news-releases/2023/october...

https://academic.oup.com/brain/advance-article/doi/10.1093/b...

> The whole point is that we are constantly finding causal, not casual relationships with our microbiome.

Both your examples cover casual relationships/correlation, and don't even try to assert causality.

I think you inadvertently proved OP's point on the high frequency of pseudoscience claims regarding human microbiome.

> It's possible that the microbiome health really is as important as some people think, but it's also possible that the role is more minor and the changes in it associated with various diseases is just incidental.

You overstate your counter argument. The role of the microbiome in disease is complex and it’s hard to nail down the exact pathology, but the chances of it being incidental is vanishingly small.

> (...) but the chances of it being incidental is vanishingly small.

I think you're misrepresenting OP's claim. OP explicitly stated there's some likelihood the influence is minor, but for some reason you're trying to refute "incidental", which is not what OP claimed.

I agree with much of what was said. My point was that they didn’t stick the landing. They overshot the mark. They did specifically use the word “incidental” so I don’t see how I could be misrepresenting anything.

It’s a good article, but I have the following criticism (i’m not the biggest expert, but I’m a biochemist):

- many of these myths are things I’ve never heard before. I’m wondering how prevalent some of these really are.

- some of these seem to be targeted towards uncharitable interpretations of ideas that could be explained more carefully

- there are much more prevalent popular myths that are not mentioned.

- I disagree about their take on how new of a field of research this is. I think they’re not taking big enough of a step back. I would say without hesitation that the field of nutrition, as a science, is VERY young. And yet it predates the study of the microbiome by a generous margin. I think this is a matter of perspective.

> many of these myths are things I’ve never heard before. I’m wondering how prevalent some of these really are.

It would be very odd for the average person to worry about who coined the term "microbiota", how many bacterial cells there are per gram, the weight of the human microbiota, etc. I'm guessing many of these myths are encountered only in niche communities that nonetheless deserve addressing—I'd guess that most of these myths don't interact with the average or median human.

These don't appear to be general-public myths, but misapprehensions from fellow scientists working in the field. Most of them are too specific ("Firmicutes:Bacteroidetes ratio", really?) to be prevalent among non-scientists.

Also, this one is curious:

- There are 10^12 bacterial cells per gram of human faeces

They first say "it is incorrect", then continue with "the real figure is typically between 10^10 and 10^11" -- that's just one order of magnitude off, on a 12-digit number. The pedanticism is strong on that one. It only makes sense if they're addressing their fellow colleagues, who are supposed to know better.

> These don't appear to be general-public myths, but misapprehensions from fellow scientists working in the field.

I am a biochemist and read a few relevant journals regularly, and that’s precisely what I’m talking about.

Here’s what may be a more charitable interpretation:

A prevalent layman’s myth is that the bacteria in our gut outnumber our human cells by a wide margin (the article quotes the myth as 10:1). That’s a striking figure to a layman and “only” an order of magnitude off from what they claim is the true 1:1 ratio.

I can't say I've ever considered the ratio of gut bacteria to human cells in my life. I find it difficult to imagine this consideration is itself very prevalent outside of people who are particularly neurotic about gut bacteria.

I’m certainly a layman on this topic and have heard this quoted often in lay forums like podcasts, and have even said similar myself.

I think it's unfair to characterize this as a layman's myth given that it was a widely quoted figure in the literature at least until 2016.

https://www.cell.com/cell/pdf/S0092-8674(16)00053-2.pdf (Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans)

I guess I could have made it clearer with better wording. I didn’t mean layman’s myth as in “originated by layman” or “only quoted by laymen” but rather “commonly known to layman”.

The intent was to distinguish it from other myths in the article that are probably only known to experts. E.g., I don’t think you’ll find many layman quoting a myth about firmicutes:Bacteroidetes ratios.

Scientists should be 100% pedantic. It's baked into the discipline.

Imagine you received a wage that was 1/10 of what it should have been, you notified the appropriate department in the company, and they wondered why is your pedanticism so strong when it is just one order of magnitude.

If my official wage was 10^12 dollars/euros/pounds sterling, I don't think I'd be worried, really. Even yuan or yen.

It's the difference between rich and poor in Venezuelan Bolivares (290k USD vs 29k)

29K USD is still more than I make now.

In biology things mostly only get interesting on a logarithmic scale. It has to do with the fact that on/off is decided by concentrations.

So I was a tad surprised for example that I had my drinking water tested for lead. It came back “clean” at 1.9 ug/L, a friend’s came back as “be careful, flush in the morning at 2.7. That does not make sense to me. Although of course a wage difference of 1.6x is pretty significant.

Imagine learning that the estimated age of the universe was off by 1 order of magnitude. Astronomers will freak out; 99.9% of the world will shrug and get on with their lives, since the number is unimaginably huge and irrelevant to their lives.

> just one order of magnitude off, on a 12-digit number

Doesn't matter how many digits are involved; a factor of 10 is pretty significant.

Depends on the scaling factors. 10x the sound energy is only twice as loud.

Only sounds twice as loud to a human observer.

I don't know. The difference between 10^101 and 10^102 seems insignificant.

Depends on context. The difference between 10^34 and 10^35 is the difference between a baby and a full-grown adult in planck sizes. For a more relevant example, a terrabyte is an unit we regularly work with that is ~10^18 bytes and an order of magnitude difference is still quite impactful (this is fewer orders of magnitude than your example, to be fair, but more than the original correction).

> I don't know. The difference between 10^101 and 10^102 seems insignificant.

Pour yourself two cups of coffee.

In one, add 10g of sugar.

In the other add 100g of sugar.

Do you think both are the same?

Compare the ratios of the exponents in your example and in mine.

I see another consideration, an implication of the other response - the domain of the exponents. For example, consider 10^101 and 10^102:

* The ratio of exponents is 102:101; not much apparent difference.

* But that doesn't specify a domain, so maybe we implicitly assume the domain is (0, 1, 2, ... >= 102). However, if the domain is (100, 101, 102) then the difference between 10^101 and 10^102 seems more likely to be as significant as the difference between 10^1 and 10^2.

> * The ratio of exponents is 102:101; not much apparent difference.

I'm not sure if you understand why this is nonsense. A factor of 10 is not small by any scale, and the relationship between 1 ton and 100kg does not suddenly become insignificant if you decide to express weight in nanograms.

Maybe instead of calling each other's ideas nonsense, we could try to learn something. Maybe next time!

The one that follows shows what they call "incorrect" is just 2X larger.

When I read the article I determined it was basically some folks on a hobby horse trying to promote their view and saying other people are wrong.

I don't have a problem with debunking absolutely made-up (no original source) numbers, but if you're sying people are wrong with a factor of 2 or 10 difference, you're just being overly pedantic.

it's impossible to know where and how an assumption will be built upon common intuition in existing science.

What if the estimate for an LD50 for a new drug going into a trial were an order of magnitude out due to one of the underlying inputs being an order of magnitude out. The worst case scenario is that things could die off that wrong number. If nor humans, at least a lot of rats...

> It only makes sense if they're addressing their fellow colleagues, who are supposed to know better.

Well, this is an article written by a medical journal asking research paper authors to stop making these common errors.

And the first reference is from a professor named Dr. Hacker, which makes it more relevant here regardless.

> that's just one order of magnitude off

"Just one order of magnitude off"?

Just?

Do you understand that this means the real world value is between 1%-10% of the initial claim?

I’ve heard and believed most of them (I am a biologist). Yesterday I came across the 1 kg of microbiome statement in Nemo in Amsterdam (a science/do museum for kids). So I consider them prevalent fwiw.

I actually thought it proven that the microbiota was seeded during vaginal birth and may lead to more issues for caesarean section delivered kids. I guess it all just sounded so logical. I know I know, that’s the most dangerous thing.

The microbiome is seeded during vaginal birth, the point the article makes is that this is only a temporary microbiome, and is unlikely to have any reflection in the microbiome vry long after birth and none after weaning.

While this is a better understanding than the parent comment, it's not quite right either.

The microbiome acquired at birth and early childhood is EXTREMELY robust to change throughout the rest of a lifetime. As an adult, it's frustratingly difficult / next to impossible to meaningfully change your microbiome. Even if you completely change your diet and you move across the world, your microbiome will be closer to what it was when you were 5 than it will be to anyone in your vicinity. This is a simplification, but the effect is spectacular.

What the authors here claim is not that the microbiome is very plastic throughout your life-- merely that it retains some plasticity in very early childhood.

Actually I can relate to those misconceptions as a person who enjoys popular science.

I like articles like this since they hopefully help me to fine tune my intuition.

One thing I didn't see in this. Probiotics. So you have an active culture yoghurt, for example, that has one or a small number of bacterial species in it. This is claimed to benefit your gut biome. But how? Surely [re]introducing these few species hardly matters, given the overall diversity?

My 2 cents hypothesis : as some food “kills” many organism (garlic for exemple is an excellent gut cleaner), you also benefit to re-fill “good” organism like those in yoghurt.

Garlic is both antimicrobial and a rich source of food (oligosaccharides) for many strains of gut bacteria. It happens to be a favorite additive to fermentation recipes for this reason.

I think you’d have to eat a colossal amount of garlic for its anti-microbial properties to have any measurable impact on your gut bacteria.

From what I read and researched online is that probiotics aren’t the bacteria you need, but are sort of good neighbors to the needed bacteria and create an environment they need to thrive by balancing pH of the gut and outcompete the “bad” bacteria and yeast.

The only thing I have to say about that is that pH is probably not very clinically relevant. The rest more or less checks out.

Yeasts are pretty sensitive to pH levels

To say nothing of viruses, which make up a huge (but not well understood) portion of our microbiome. Current estimates put the number at over 100,000 unique species and perhaps a few hundred trillion viruses residing in the human microbiome, far eclipsing endogenous and bacterial cells.

Almost all food can be considered "probiotics", as pretty much everything is covered in microbes and provides food for microbes when eaten. A diet that promotes a healthy microbiome is going to be much more effective than supplementing lactobacilli or whatever.

>A diet that promotes a healthy microbiome is going to be much more effective than supplementing lactobacilli or whatever.

This may be generally true, but there may be situations where it is significantly better to do both, if we are talking about probiotic pills. Needs more research before making definitive statements (other than the reasonable stance that careful refinement of diet should always be the starting point when possible).

Fermented foods are on another level, though. It appears that increasing consumption of fermented foods is just plain good for us as a general rule. May someday be a standard corollary to "eat your veggies" for overall health and longevity.

That's why so many ancient cultures made beer. Basically every culture that began eating grains immediately also started fermenting them into beer.

It wasn't for the alcohol, that was normally very low in c. 5000BC beer anyways. It was because people that consumed it were healthier than those that didn't. Fermentation is nutritius and beneficial beyond alcohol/calories/potable water.

Two thoughts:

a) By introducing a large number of one or a couple of particular species, you're influencing the demographics.

b) The type of creatures you find in fermented foods are exactly the type of creatures who can help you digest those foods.

Some studies show bacteria from fermented foods colonizing the colon and others do not, although regular consumption does tend to marginally increase microbiome diversity (a generic and in many ways crude measure of GI health). In theory, an optimally functioning GI tract would be killing a majority of the live bacteria long before they reach the colon via a combo of enzyme activity, stomach acid, bile, pancreatic enzymes, and immune activity on the way down. What has been more consistently shown is fermented foods causing decreases in GI inflammation and other positive impacts. Some researchers now believe that many if not most of the benefits come from all of the microbial action prior to consumption.

Fermenters such as Lactobacteria do a lot of work for us ahead of time, such as breaking down so-called 'anti-nutrients' and converting low-bioavailability nutrients into high bioavailability nutrients, producing anti-inflammatory metabolites, outcompeting pathogenic bacteria and fungi, and so forth. Bacterial fermentation has even been shown to break down pesticides [0], aflatoxins [1], and other potential contaminants present in the raw food. I wouldn't be shocked if microplastics and/or PFAS gets added to that list, at least under certain conditions, in the coming years.

[0] https://www.tandfonline.com/doi/abs/10.1080/10408398.2012.67...

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737493/

> Some researchers now believe that many if not most of the benefits come from all of the microbial action prior to consumption.

That seems counter to the whole idea behind modern research on the importance of the gut microbiome and a throwback to the thinking of the previous century.

Certainly some of the work of bacteria is done before but that’s well known as many foods are fermented but the cultures are killed or pasteurized afterwards. Classic American yoghurt was like this, but there’s clear benefits to yoghurt with live cultures. Even if many bacteria don’t colonize the gut their presence in the food or taken separately appears important.

In my opinion the evidence is overwhelming that actual probiotic bacteria themselves are important, not just their by products in the food. Our immune system detects healthy bacteria both living and dead and lowers inflammation in response, etc. There’s a lot of research on the topic and good summary research (1, 2). The presence of the bacteria also change the gene regulation in the intestines.

Fecal transplants can directly treat diseases, or trigger diseases with maladaptive bacteria (3).

1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512487/ 2: https://www.sciencedirect.com/science/article/pii/S277250222... 3: https://www.frontiersin.org/articles/10.3389/fimmu.2022.9917...

Yeah but fecal transplant bacteria isn't comprised of the sort of transient bacteria generally found in probiotic sources. It leads to a kind of hard-reset for gut flora. There are few sources that offer bacteria that will persist in the gut, I think I read kefir is one of them, but to what extent I'm not certain.

Even transient probiotics provide benefits too. Even when killed by stomach acid they trigger certain beneficial pathways. Many, perhaps most, traditional diets from around the world featured some live-culture fermented dish as a staple. Likely our bodies evolved to expect large daily exposure to certain healthy bacteria, and societies that ate live cultures with those bacteria would have better health.

Fungi will start feeding on plastic in the environment relatively soon. Digesting plastic in an animal digestive tract is a tougher nut to crack, similar in principle to digesting celulose.

Citation?

yeah I always found it a little counter intuitive how eating bacteria would be good for my gut insofar as most the GI tract is meant to be major gauntlet for bacteria.

But I get dodgy IBS-like issues eating spicy food but consuming fermented foods in proximity really helps settle the stomach. ie Kimchi affects me less than other spicy dishes while eating natto after having a lot of spice can really help. Ditto for yoghurt but I'm lactose intolerent and so many lactose-free yoghurts are full of crap

What crap is in lactose-free yoghurt? Afaik they add lactase which lactose tolerant ppl still “produce” after weaning. So the lactose is simply “pre-digested” into glucose and galactose.

most dairy free yoghurts (and lactose free yoghurts) are full of stabilisers and sugar

Could be any other reason.

BTW, you can make your own yoghurt, it’s very easy.

(heard from probiotics researcher)

Probiotics can potentially be highly effective, but you must eat some specific probiotic that helps you. The science of figuring out what type of probiotic you need is not very advanced.

Pharmasies sell probiotics for consumers and there are also foods that claim to have benefits, but they don't usually work, or work only by accident.

If you have been taking antibiotics, your biome is likely out of order. Fecal transplants can help.

One anecdote. I had a friend with ongoing gut problems for years and tried giving him probiotics in pill form and it didn't really do anything. But recently he's discovered taking garlic juice seems to make things better. Presumably it kills of whatever bacteria that were upsetting his gut.

This was something interesting that I read recently on (reducing) staph colonizations:

https://news.ycombinator.com/item?id=34713431

This came well after the University of Iowa protocols for mitigating staph prior to surgical procedures (it's all about the nose, a favorite place for staph to inhabit):

https://now.uiowa.edu/news/2013/06/be-gone-bacteria

Would someone please do all of us a favor and give an educated overview of what gut bacteria actually is and does?

I honestly have no idea and the article just assumed I do.

Analogous to the macro environment of flora and fauna; an ecosystem of microorganisms exhibiting the same evolutionary patterns and dynamics inside of host bodies

Read “I Contain Multitudes” by Ed Yong. A very approachable book for anyone.

It’s a nature paper so it’s directed towards scientists not the general public. But also scientists not necessarily doing research in the space.

I’m happy to see a bit of myth busting going on. The space is in its infancy but wow do I ever see university press releases touting “microbiome is connected to disease X” a lot and it’s usually based on pretty flimsy evidence.

The field will mature over time and no doubt find some interesting connections to human health, but it seems like there is a mad rush to “keep a healthy microbiome” when in fact we don’t even know that much about what a healthy microbiome looks like beyond a few obvious diseases like c. difficile.

From the article:

> As examples, Clostridioides difficile can be carried asymptomatically throughout life, and only cause problems in older age when the host is immunocompromised and treated with antibiotics

It seems that even c. difficile is not obviously "bad" .

I noticed this too.

My comment was more around the strong connection between antibiotic use, C. difficile overgrowth and resulting harm to health.

But that comment is a good point that simply the presence of a bacteria doesn’t tell you anything by itself.

Reminds me of the people who harbor MRSA in their nose. MRSA can cause a serious infection, but apparently for some people it doesn’t.

> The average human stool weighs less than 200 g.

Guess I'm not average. But TBH, I've never weighed my poop, only occasionally estimated.

I always figured if I took a healthy dump before heading out to run, that's be a pound less crap I had to haul around. ;)

One wishes there were a version of this article for science journalists.

And, one wishes that a university class on scientific ethics asked students to read this article with a critical eye and figure out what they can learn from it.

Myths about human-health topics spread faster than truth sometimes. cf. stomach ulcers and "stress" vs. pylobacter. It's hard to stop that. But it's easier to stop if we're aware of the myths.

> "“The human microbiota weighs 1 to 2 kg” --- The majority of the human microbiota resides in the colon,

They give a reference which appears to not have been cited by anyone???

Yet it's easy to find references (second result in Ecosia search engine).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313343/

I used to be bloated before my doctor advised me to try eating more bifidus with the help of a popular yogurt brand. It works like a charm: almost no bloating anymore if I got my morning yogurt but gaz seems to come back in a day or two of bifidus abstinence. I’d love to find a diary-free alternative.

If you have Forager where you live, I'd highly recommend it. It's a cashew based probiotic.

https://www.foragerproject.com/

Thanks a lot! I’ll give it a try.

Have you tried kefir?

Regular milk is unbearable to me, and yogurt is better but not too much.

Kefir on the other hand made a significant change to my day to day "gut health".

**fast edit: and I really mean significant change. kefir + no sugar (low sugar diet)

If someone is making their own Kefir, the grains can also be converted to water Kefir to ferment something non-dairy.

So do I still have to drink kombucha?

Why do you believe you have to drink kombucha?

I don't really. It was just a silly joke based on the notion that kombucha is supposed to help your gut microbiome but many people think it tastes gross.

The cool kids brew/drink kefir now.

If you don’t have middle eastern or Slavic tastes you’ll probably think it tastes gross tho.

I think I read that the slavs don't like sour things and preferred to drink kefir during a state it was early stages of fermenting / bubbling, which is rather sweet, if you've ever made it yourself.

Yes, I do the secondary fermentation which involves decanting it into a mason jar when it starts to separate, with some fruit pieces and letting it go for another 2-3h before refrigeration. This takes off the tartness and makes it a little creamier.

My coworker, who is Iranian, usually just drinks it straight (I don’t know about the fermentation time) or with a little mint and salt since this is typical for West and Central Asia: refreshing because of the hot climate and similar to drinks like doogh or ayran.

Slavs eat a huge amount of fermented cabbage

And sour soups like żurek (soured rye) and the dill pickle based рассольник (rassolnik) and zupa ogórkowa.

I like the taste but find the amount of added sugar dubious, in products sold.

It was a great joke, fwiw

Thank you! This is a tough crowd, got a lot of down votes on this one

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