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A primer on why microbiome research is hard (owlposting.com)
91 points by abhishaike on Sept 1, 2024 | hide | past | favorite | 26 comments


Fascinating article.

Slightly-off-topic:

This article presents the hard science as exceedingly difficult. I kinda suspect part of that is scientists have this attitude of acting completely blind to the hundreds of millions of years of evolution that made us what we are.

For example, if we suppose that microbiome is important to health, and suppose that all human behaviors (e.g. hand-shaking, kissing) I think it gets us pretty quickly toward some great avenues to test. I almost wonder if the imperfect sanitation conditions we evolved in might have conferred some ability to exchange fecal microbes.

Now obviously this doesn't really solve the fact that sequencing a microbiome is incredibly hard. But even without sequencing a microbiome you could probably do a blind test of saliva-swapping vs water and see to what degree this affects self-reported measures. Or if that's too hard to get past IRB, have one towel that's been touched by 50 people and one towel that's completely clean, and see if touching that has any subjective effects.

It feels like the kind of things you could test on 1,000 students in a weekend for free.


Thanks for this article. I think it places a lot of the gut microbiome studies and findings in context.

As a note for the author in case they are reading - you should do a quick Find/Replace on the article keyed on the word "git". There is more than one instance in the text where it clearly should read "gut microbiome" (or similar) and instead reads "git microbiome".


> There is more than one instance in the text where it clearly should read "gut microbiome" (or similar) and instead reads "git microbiome".

> For example, the git microbe Bacteroides dorei has become increasingly recognized for its role in heart conditions and T1D.

I find the word "git" perfectly appropriate here.


Perhaps I am mistaken and "git" in this context is simply an acronymn for "gastro-intestinal tract". Maybe capitalization would make this more obvious to those of us not directly involved in that space or a definition of "git" somewhere in the paper that defines use of the term in that context. If that already happened then I missed it.

Thanks for pointing this out.


“Git” is a pejorative. The GP was suggesting that this microbe deserved being called a “git” for its deleterious effects.


Either that or version control causes hypertension for some folks…


Or worse, Type 1 diabetes!


"Check with your doctor to see how many units of insulin you'll need to inject with each merged PR."


Regarding the cancer microbiome controversy, I am on the side of the skeptics. The issue of mis-identifying human sequences as bacterial (due to human DNA contamination in bacterial reference genomes) is a big problem, and the authors of the original study didn't properly filter out human-derived sequencing reads. That error, by itself, invalidates the paper.


Thanks for the link. Very important research and I’m thankful for the scientists taking it on.


More like this please!!!


I kinda roll my eyes when I hear anything about the microbiome because it so rarely turns into an actual therapy.


What about yogurt, kombucha, kimchi, etc.? Those have been around and globally common "forever". They're low profile, though, in their ubiquity.


Aren’t those “the ones that mother gives you that don’t do anything at all?” like all the other scammy probiotics?


>scammy probiotics

It is pretty understandably where you're coming from. The industry has no standards/certifications and thus a free play for anybody. I for example haven’t found anything effective for me. For my dog though the FortiFlora noticeably improves the output (fortunately we have no serious issues here, it just like any dog owner you watch your dog's output as an important health indicator and over years, my is 15 already, you get to become a big specialist on your dog's output and notice any worsenings or improvements).


I don't know. I'm seeing articles suggesting our diet used to contain more fermented foods but inventions like refrigeration has altered our diet to no longer lean on fermented foods as much.


And what proof is there that that stuff is good for your health?


One obvious way it is good for health is that the fermented foods stay fresher longer so that eating them doesn't make you ill. A lot of people use them to help their microbiome recover after they've taken a course of antibiotics. Here's 411 pages of proof:

https://pubmed.ncbi.nlm.nih.gov/?term=fermented+AND+foods+AN...


Isn't that the whole point of the article? Microbiome research is hard? In this case, we're just left with trying to extrapolate loosely based off of trends.

There's nothing to suggest that these things are bad for your health (as far as I'm aware) and there's a hypothesis (not a theory) that these might've contributed to gut microbiomes in the past. But, rather than conclusive proof, it might just be something low-stakes that people can try until more hard research or data is found that has a more conclusive direction, even if it disproves previous hypotheses.

Until then, we're left making best-guess efforts with no conclusive proof. But, suggesting that these have no benefit is also incorrect until we have conclusive data to suggest otherwise. Hence, the point of the article: figuring out stuff about the microbiome is hard.


Anyhow I eat a lot of yogurt and love kimchi, but to be kombucha is only slightly more palatable than battery acid. (e.g. heartburn in a bottle)


Scientific proof: see article.

I'm actually with you on the popular culture BS and commercial bandwagon part of everyone talks about kimchi now etc.

But then anecdata of one: before all the kimchi craze and all that started in earnest I was looking into why even an alcohol free beer would give me the worst migraines ever. Other foods would do it too. Alcohol would be even worse.

A lot of googling and trial and error later I found that the microbiome most definitely is involved. In fact, some of these yoghurts that people peddle as good for you would trigger my migraines. Danone Activia for example would give me guaranteed headaches. Too many tomatoes would too.

Really anything histamine producing would which explains why alcohol was doubly bad but not necessary.

And using the right kind of probiotic, which does not include (too many) histamine producing strains but notably does contain "bacillus subtilis" did it for me. And yes I tried a lot before this and I do think but can't scientifically prove that it's that one because most if not all others have been part of other ones I tried before (both in combination probiotics and single strain versions).


> anecdata of one

anecdatum ? :)

Similar symptoms but not migraine level here, but did you ever check food allergies? That could do much of the symptoms too.


I tried many things including going to doctors. I was sent to an allergologist by my GP for example. The GP was very understanding but out of expertise.

The allergologist though after hearing about my symptoms and triggers said he could do an allergy test series but he thought it would be waste of time and I must be imagining things.

That was the end of relying on doctors for me and I just started experimenting and figuring stuff out myself.

In a sense it is a food allergy I suppose. Dunno what the actual definition of an allergy is.

Certain foods have naturally high levels of histamines or cause the body/microbiome to generate them. It's what makes the hangover when you have one. I just basically got hangovers from eating too many tomatoes or awesome blue cheeses. Or from drinking Actimel. Or from taking Zinc pills (which happened to actually contain histidine - on purpose because it's supposed to be good for you, but which is a precursor to histamine which explained why the zinc pills gave me almost instant migraine type headache).

Alcohol is doubly bad because many alcoholic drinks contain histamine to begin with but in addition the alcohol itself inhibits histamine metabolization. Double whammy and why a tiny bit of Laphroaig just for the awesome peaty taste would result in a headache as if I had had two or three bottles of super sweet wine.

Many probiotic experiments later, I can now eat Lasagna with extra tomatoes in the sauce for lunch, have a nuts and a whole blue cheese wheel with red wine for dinner and have multiple whiskey shots without any headaches at all. Not that you'd want to actually do all that in a day probably :)


> Dunno what the actual definition of an allergy is.

I think immunoglobulin E antibodies for whatever.

https://en.wikipedia.org/wiki/Immunoglobulin_E


the proof they are good for your health is they taste bad


I keep reading your sentence above, and i remember your username as seeming to have a similar overlap with my background, and so i keep thinking you sound like you're describing homeopathic tinctures. i might have missed claims about kombucha, or probiotics, to be fair, since i just probably randomly like kombucha, whereas you don't, and i didn't worry about scams, just non toxicity.

i say that having gotten in amusing question sessions with vendors in organic groceries about the homeopathic stuff, years ago, until i got bored with it all.




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