>However, there is some light evidence that the variation I see is not just intra-day variation. Specifically, there are several species that stay consistent in frequency across all samples: e.g., Neisseria subflava, Streptococcus viridans, Streptococcus oralis.
Disagree. You can not make that claim without sequencing your mouth's microbiome in the absence of probiotics for a month as well (and, really, many more than one persom's). Was your diet controlled all month? Oral hygiene habits? Any of a million other variables?
Also, it's worth pointing out that the study was designed to test one hypothesis, and you need to be very careful about looking at further claims. This test only really provided evidence that these probiotics don't introduce L. reuterii.
PSA: If a probiotic is on the shelf, not in a cooler, it's probably not worth buying. The best companies certify the count of organisms at time of manufacture, but no counts are guaranteed at the shelf. Probiotics are living organisms and ought to be refrigerated for max lifespan.
You can get refrigerated probiotic supps at a place like Whole Foods.
Source: I used to work in the industry.
When I asked my doctor about which kinds of probiotics are most effective she specifically mentioned refrigerated vs non-refrigerated is not a way to identify quality or effectiveness unless you know the specific strain(s) needed cannot be made shelf-stable. This lined up with asking my endodontist after they prescribed some antibiotics for a tooth infection. They did warn that the use by dates are a bit bull, not to stock up on them as they do deteriorate in quality with time, and not to try to keep even the shelf-stable ones above room temperature.
Maybe I misunderstood what my doctor said, maybe my doctor was just wrong, maybe it's actually extremely nuanced, maybe it's something I hadn't even considered. I guess all I'm saying is it's probably better to talk to your doctor(s) about it than follow self-sourced (in both the above and this comment) medical advice from HN.
Also frankly, doctor =/= expert on probiotics.
None of their training really addresses that and while they might be more qualified to read research than random layman I would not in general ascribe authority to what a random practitioner has to say about probiotics. Frankly, the research on probiotics is still very much in its infancy and a LOT remains to be figured out.
Absolutely, if you have access to domain specific experts or researchers than that should trump whatever your more generalized expert will say.
Also right to highlight that just because there exist specialist in something does not mean we have the full or correct understanding yet, it's just your best place to find information regarding it unless you want to go join the field.
Great points!
> doctor =/= expert on probiotics
Medical microbiologists would love to have a word with you. Medicine and medicine-adjacent disciplines each develop institutional knowledge that percolates from each specialized discipline.
> …the research on probiotics is still very much in its infancy and a LOT remains to be figured out.
I’m curious who you think does the research. It’s certainly not Bubba from down the creek.
They don’t develop treatment protocols or testing modalities either. Knowledge gets disseminated as best practices and gets applied as needed to different specialties.
If probiotics is what you’re after, why not eat or drink something fermented?
>self-sourced
It's not "self-sourced" whatever that means (like that's a bad thing per se?). I saw the sausage being made and I spoke to the sausage makers. The source is the sausage makers, not me. Sorry I don't have a link. These facts may or may not be trade secrets.
"Self-sourced" as in both of our comments are hearsay: we say we heard this information from someone and our source for that is only us saying so. That's pretty bad in terms of what others can actually do with that information (from either of our comments). Not just because hearsay can be faked, but more because it's unquestionable, untestable, and the quality of the information has almost always greatly degraded compared to the source.
This doesn't mean the comments should be assumed to be false any more than they should be assumed to be true. It also doesn't imply we necessarily have some way to provide an actual source either. Just that folks will have to go elsewhere if they want any certainty about this information, since we didn't provide any as random usernames on a message board saying we heard something before.
> maybe my doctor was just wrong
Yes, doctors are similar to mechanics or any other trade, in that some simply suck.
Some got Ds.
“ and not to try to keep even the shelf-stable ones above room temperature.” - hate to ask, but night brain kicked in - could I trouble you to give me an alternative way of phrasing this? I keep parsing it as “don’t even bother trying to keep probiotics warm”
No night brain, just a good splice on my part after editing that sentence down :). stavros has a great rewrite already, but an even more succinct one for just the particular snippet could be:
"even shelf-stable probiotics should not be kept above room temperature".
The last step in the receipt of my first beer batch stated: "now store it at a warm place around 21ºC".
No way I could find a place this cold during Rio de Janeiro summer.
They gave it as a defined term with a pdf copy of https://www.goodrx.com/drugs/medication-basics/which-is-the-... describing the ranges - I just neglected to include all of that detail in my comment :). Another example of why it's great to discuss with your doctor instead of advice from forum comments! Googling around, apparently these values are standardized for pharmacology in the US by the USP, other areas may have other standards.
Hope that helps!
"Even the ones that can be kept outside a fridge shouldn't be kept above room temperature".
> The best companies certify the count of organisms at time of manufacture
The best companies certify the viable count at expiration, I've seen many that do.
There is a difference between probiotics in live culture and shelf stable products but both can be viable methods of delivery.
There are some newer types of probiotics (called "spore-based") which claim better shelf stability (don't require refrigeration) and resistance (to populate further down the digestive system). But you're absolutely right, they tend to die off pretty quickly (be extra weary of ordering them online, especially during the summer if they're going to sit around in a hot delivery truck or mailbox!).
That is more around solving a different problem than shelf-stability, which is the fact that most probiotics targeting the intestines don't survive in great measure beyond the stomach.
They sell a yogurt starter that is purportedly Salivarius and ruteirii culture over at Beazos' Clubhouse. I haven't had it tested but it's way easier than the usual Bulgarian microbes. Assuming the cultures are as labeled, I have to imagine eating live culture yogurt is more likely to propogate than loszenges made in a factory though.
I've made the L. reuteri "yogurt" from the BioGaia Gastrus tablets from amazon and it works well. First batch is a little watery but after that it pretty much looks like greek yogurt when I use half and half.
A very naive question: why are "dry and on the shelf" not worth buying, when so many of the food-related microorganisms obviously work fine through such distribution (baking yeasts, various yogurt starters, cheese molds, etc.)?
Yeasts and fungi produce durable spores. But most gut bacteria do not form spores. When they dry out, they die.
Why not run an experiment like this post: take a probiotic capsule, put its contents in a growing medium; after a day or two, sample from the medium and send it in for testing, and see which strains actually grew?
So I shouldn't spend money lactibiane buccodental oral probiotics in pills?
what kind of cooler, near zero or just yogurt level temperatures ?
Freezing has potential to cause damage to the organisms, safer to refrigerate (and consume asap)
does this apply universally to bacterial strains ?
Yes
The Internet almost universally disagrees, based on a quick search:
https://seed.com/cultured/probiotics-refrigeration-storage-g...
There's a difference between "choosing one over the other" and the original claim of shelf stabilized probiotics being not worth buying.
On a few occasions when my dog has gotten sick, or needed antibiotics, shelf stabilized probiotics cleaned their digestion right up.
Are strains that only survive when refrigerated probably a higher count? Maybe. Are there stains that are better but can't be freeze dried? Probably. Are there shelf stable probiotics that are worth buying, especially if you don't have access to refrigerated stuff? Absolutely!
Thank you
Nice experiment and writeup!
On a tangent, nice to see Plasmidsaurus using Emu [1], which has been shown to work great for 16S ribosomal RNA analysis on ONT by basically everyone I've heard who tried it. It has a nice algorithm for predicting if variants are due to ONT sequencing errors or are true variants, based on an expectation maximization algorithm, and thus working around the somewhat limited accuracy in ONT reads. Pretty clever stuff.
And if you want to run your own analysis on the raw data using Emu, you might want to try out our Trana pipeline built around Emu in Nextflow [2]. Apart from running Emu, it does some of the preprocessing like filtering, as well as exporting as Krona diagrams etc.
We're just putting it through validation at the clinical microbiology lab at Karolinska here in Stockholm right now.
The main caveat worth mentioning is that the choice of database seems to be able to affect results quite a lot in some cases.
I love that this is something that is feasible for someone to just do right now as a hobbyist or blogger. The prices involved here are very reasonable and well within reach of someone wanting to do some project, though not yet at "sequence your microbiome every day" levels.
I hope we see a lot more posts like this in the future.
Yea; Plasmidsaurus slaps. Especially if you live near one of the drop boxes. (e.g. a research university) $15/sample, and they email the results the next morning. This sort of service is enabled in part by nanopore sequencing.
I have just used them to dork around with my home lab to validate cloning results. Now I want to try something like this!
I want this for nasal microbiome. I think modern living is wreaking havoc on our upper respiratory track. We need to find a way to regenerate or improve nasal cavity microbiome.
Just don’t get caught insufflating your probiotics during lunch hour :)
I think your best bet is first curing your allergies. That's what I've been working on for 5 years: www.wyndly.com
how do you test for allergens? i did 5 years of immunotherapy shots, twice weekly at a doctors office and i had to stay 30 minutes after each shot for the anaphylaxis risk. it worked quite well but it was really inconvenient.
Fresh air
Nasal rinsing may help. In my case, it reduced my number of colds per year from 6 to approx. 1, and they also tend to be milder. This was likely accompanied by some change in nasal microbiome as well.
Only tangentially relevant, but I’ve dealt with mouth and gut microbiome issues my whole life, the latter exacerbated by a strong antibiotic I had to go on in mid 2017 for a super resistant staph infection. L Reuteri supplementation and “L Reuteri yogurt” was one of those alternative methods I read about (though I’m skeptical that reuteri is the dominant strain in this “yogurt”)
Doctors don’t really care to look at these kinds of issues. It took years of suffering and autoimmune issues (particularly muscle spasms and joint pain) alongside gut problems before I demanded a gastroenterologist test me for H pylori and SIBO: I was positive for both.
H pylori was a painful treatment process, but I cleared it after one round of quad therapy. SIBO on the other hand, a condition I think we hardly understand, has been hard to deal with. Many rounds of rifaximin with very minimal relief and no real answer as to how to deal with it.
Doctors are hesitant to help, so I’ve resulted to a lot of personal experimentation to deal with it. The only thing that ever worked (and it’s just anecdata so unsure) was sulbultiamine supplementation, but I can’t actually get that anymore and normal thiamine doesn’t help.
This is all to say: I think microbiome is supremely important to health, very few things seem to really impact it, and doctors are hesitant to deal with these systems at all. I’m sure FMTs will become much more popular for a variety of conditions, but it seems like it’s a real risk where not only might someone else’s microbiome not be a fit for your physiology, but you could be inheriting a variety of risks the donor is susceptible to but you are not.
I am not a doctor and much of what I’m saying may be wrong. Don’t quote me please.
> Doctors don’t really care to look at these kinds of issues
Perhaps for good reasons?
The science is messy, there are few proven interventions and every woowoo worrywart will be pestering their doctor. Your doctor is in an unenviable position.
With doctors in New Zealand, my one trick is to find good specialists and pay them privately.
I believe that a GP only helps point you in the right direction. Our public health system is mostly too overloaded to help (unless you have a critical problem and your GP helps you get in a queue).
Not sure what helps in other countries.
But I 100% agree that you need to take responsibility for healing yourself. Only you have the motivation, and the context and experience to judge your own problems -- however one needs to take care not to get caught in irrelevant or misleading deadends (especially when mislead by corporations or alternative woowoo freaks).
> Doctors don’t really care to look at these kinds of issues. It took years of suffering and autoimmune issues (particularly muscle spasms and joint pain) alongside gut problems before I demanded a gastroenterologist test me for H pylori and SIBO: I was positive for both.
I went through a similar post-antibiotics gut nightmare. There are good doctors and there are bad doctors and like everything, there are fewer good ones than bad+average ones.
Seems like you got testing and treatment eventually, I'm sorry it didn't work better; I'm replying less for you and more for anyone who encounters similar. Shop around for your docs!
I got tested very quickly for both H Pylori and SIBO in 2019 on doctor suggestions, I'd never heard of either. Sounds like this was probably around the same time as you went through this based no the antibiotic course that messed up your gut being in 2017).
I went to three doctors in six months, the one that did the testing was the second one. The one who was confident in their knowledge but didn't do anything, including the testing -> immediate no-return-visit from me. The one who said "we don't really know how this works" but also didn't do anything -> no return visit, but appreciate the candor. The one I went back to is the one who said "we don't really know how this works, but let's test for these other things we've learned more about recently, and let's also try some experimental/off-label things." I was actually negative for both of those things, so there was even more random stuff beyond that, but the only one the doctor I liked was really resistant to was a poop transplant, though personally... seems like the only known way to repopulate some of the shit, pun intended.
Not a doctor either.
Japan seems to love creating fat soluble forms of thiamine. I've been experimenting with a form of thiamine called TTFD. TTFD is synthetic, there's a natural form called allithiamine, derived from garlic. There's also another form called benfotiamine. All of these are fat soluble and highly highly available forms of thiamine. TTFD in particular is associated with paradoxical effects where a person can have a temporary worsening of thiamine deficiency symptoms when first consuming TTFD. Thiamine is generally considered very safe, but these supplements are pretty hefty doses, so I would suggest treading lightly.
There's also some thinking amongst some doctors that sub-clinical thiamine deficiencies being more common than most doctors realize [0] [1]
[0] Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition
[1] https://www.sciencedirect.com/science/chapter/monograph/pii/...
I have been wondering about these oral probiotics for a while. I have used BLIS K12 lozenges before and had a strange experience- it seemed like they changed my baseline for what I could detect as fresh/clean breath and I began noticing everyone else's breath (which isn't exactly pleasant, even if it's not bad per se). I never asked anyone or received feedback about my own breath personally but it made me very curious what anyone who's breath I noticed would have sensed.
I would love to see this same analysis with a gut probiotic! I am never convinced if I'm wasting my money, which strains are best, should I do refrigerated or shelf-stable, etc.
Anecdata/placebo/whatever: I use BioGaia's Gastrus tablets and they increase my quality of life noticeably, and I can tell when I've been off them for a while. I got refrigerated deliveries of probiotic yoghurt drinks for a while previously and in addition to the faff, didn't notice as good results.
Additional Anecdata: I head about BioGaia's Gastrus tablets here on HN a couple of years ago and they have dramatically improved my wife's quality of life as well. She suffered from significant GI problems. We bought a pack of the BioGaia tablets based on an anecdote here. Within about 3 weeks her year-long GI problems were gone. She discontinued the tablets and the GI issues stayed away. About 18 months later, after a period of heavy stress and travel, her GI issues returned and then disappeared again after another round of BioGaia tablets.
Thank you both for the anecdata!
As far as I am aware, fiber has infinitely superior research behind it with far more drastic effects. Just take fiber if you're worried about gut health imo.
I agree, but if one has ever taken an antibiotic then they should replace the bacteria that they lost? Strong antibiotics completely destroy the gut biome
The research doesn't strongly support probiotics even in that case one way or the other.
Yes, feeding good bacteria is the best bet. Probiotics are transient, they don’t colonize.
How do they get there initially?
The environment we live in and the foods we eat are hardly sterile.
There is also a significant microbiome on your skin.
Any opinions on using pure xylitol to stamp out streptococcus mutans and improve the oral microbiome.
A surprising amount of variation from day to day even.
i remember reading about "lumina probiotic" Has anyone done research on it since, reviewing thier claims ?
their claims on their website:
replaces S. mutans, alters oral microbiome, reduces acid via ethanol metabolism, produces antibiotic, freshens breath, brightens teeth, lasts decades. etc
i am very skeptical of it
I recall they were offering a few people mail-in swabs to test if the colonization had taken hold, but haven’t read any follow-up.
Hmmm makes me want to sequence by own oral biome just for kicks or my gut flora - two sides of the same system. That would be neat and I would definitely pay $100 for either if it included an analysis.
the supplement industry is ridiculously sketchy and virtually unregulated wild-west
and probiotics are the absolute worst of the industry with endless lies in claims and products that often test with nothing of the claim in them
if you want to try probiotics
1. start with a single strain probiotic, multi-strain are often lies
2. try an extremely well known/proven probiotic
want to know something is happening? try lp299v Lactobacillus Plantarum
it's cheap, it's been studied for 30+ years so lots of trials and proven claims
it won't colonize, no oral probiotic will colonize, so you have to keep taking it or it's gone in a few days from your GI
Fun fact: kombucha is an excellent source of probiotics and is refrigerated.
I used to turn my nose up at it, but I got some branching out at a beer bar that tasted pretty good (0.5% ABV so you'd puke from too much liquid before getting drunk). It seemed more of a breakfast drink so I had a few ounces every morning. Most regular I've been in my life. That said, the "evidence" presented in the article should not be considered due to the lack of controls (just look at the variance between day -4 and day -1). Both this comment and the article are anecdotal.
But kombucha is a lot cheaper than manufactured probiotics, refrigerated, and the drink is acidic so the bacteria in the drink should already be well suited to the stomach pH (1-3 vs 2.5-3.5 kombucha).
interesting and well written article. I would imagine what you eat, amount of saliva, dental hygiene, and a lot of other variables would affect your oral microbiome. what would be a better test is for people with "red complex" bacteria to take this and see the results. the fact that it didn't colonize tells me this is pretty much useless like most probiotics https://medicine.tufts.edu/news-events/news/are-probiotics-a... the author concluded that they will use it again only because of the taste, not because it works.
This article is basically cargo cult biotech.
Tech bro woo at its finest. Can’t wait until they discover crystals.
Wasn't there recently a discussion of a risk of methanol formation from an ethanol producing strain? I sure hope that none of your strains produce ethanol.
Slightly different point but many bacteria in us right now also make lipopolysaccharide (LPS). If it were purified and injected iv, the LPS in me could probably kill me 1000 x over.
Nothing about this discussion was about injecting anything.
LPS is a critical component of gram negative bacteria, like E. coli.
We evolved LPS detection so long ago that it's in our innate immune system instead of adaptive immunity. It's so ancient we share this immune function with fruit flies.
LPS detection is so good and immediate because it's tuned to pick up single instances of LPS molecules. Not a few nmol. Single molecules. Detection will trigger inflammation and immune scale up to deal with the problem.
If you go injecting LPS or E coli into your blood stream, of course your own body is going to kill you. It'll freak out and think WW III has started and begin firing the nukes in every direction to stop it.
This is septic shock.
Why not? Ethanol kills competing bacteria and is only produced in microscopic quantities.
Methanol is produced by a lot of bacteria, almost every human produces it within their body.
Isn't methanol a strong poison? I do not believe that any probiotic or native strains produce it.
Chemically the problem with ethanol is that it's too close to methanol.
From Wikipedia:
”Small amounts of methanol are present in normal, healthy human individuals. One study found a mean of 4.5 ppm in the exhaled breath of test subjects.[19] The mean endogenous methanol in humans of 0.45 g/d may be metabolized from pectin found in fruit; one kilogram of apple produces up to 1.4 g of pectin (0.6 g of methanol.)[20]”
”Ingestion of as little as 3.16 grams of methanol can cause irreversible optic nerve damage, and the oral LD50 for humans is estimated to be 56.2 grams.[66]”
19: https://iopscience.iop.org/article/10.1088/0967-3334/27/7/00...
20: https://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.1997...
66: https://aoemj.org/journal/view.php?doi=10.1186/s40557-017-01...
It doesn't mean it's safe to risk adding to the burden. The danger is that low-grade non-acute toxicity over the natural level could still be harmful over time. All it could take is one mutation.
Eat 30 different types of fruits and vegetables every week. There is no 'hacking' your way to a good microbiome via these pills.
Unfortunately self-testing something like this isn’t trivially cheap, so the self experimenters tend to skip the very important control step.
This happens a lot when people discover that you can order your own bloodwork. Reddit supplement and biohacking forums gets a lot of posts from people sharing bloodwork from two different dates and concluding that the changes are entirely due to their supplement regimen. When you’re only getting a couple tests it’s not easy to see that even day to day variations in these tests can be very large. Even timing of tests during the day, how you slept, or what you ate can have a lot of impact on many tests.
Doing some basic controlling without taking the supplement is important. Doing double-blind tests on yourself also isn’t that hard if you put some effort in. There have been some surprising results from people doing controlled tests on themselves and discovering that the supplements that looked promising on paper were either doing nothing or were trending toward being negative. Gwern’s experiments with magnesium supplementation which were generally flat with hints of trending toward being negative are a good example. That experiment was a good reality check during the era when the popular narrative that we were all severely magnesium deficient and the solution was high doses of magnesium for everyone.
Well, they did say "light evidence" rather than "proof".