https://www.theguardian.com/lifeandstyle/2024/dec/01/the-bra...
There's a lot of controversy around this[1], because contamination is possible and it's known that the blood brain barrier weakens with age. The sample are all from older individuals.
[1] https://www.news-medical.net/health/Is-there-a-brain-microbi...
I don't see the point of the samples all being from older individuals. Even if it exclusively occurs in older individuals (unlikely), it would still mean that the blood-brain barrier is not 100% effective (which we already know to be true).
Evidence is scarce and the article is talking about brains with active illnesses. It could be that there isn't any microbiome normally but if the safety mechanisms fail and bacteria colonize the brain, that would cause the illnesses described.
They compared them to control brains, which also had microbes.
> It could be that there isn't any microbiome normally but if the safety mechanisms fail and bacteria colonize the brain, that would cause the illnesses described.
That would describe a scenario where the blood-brain barrier isn't 100% effective, no? If it's not 100% effective (which we know to be true), it is also seems unlikely that 100% of the things that cross the blood-brain barrier cause something that we currently consider a disease. Heck, in healthy individuals, latent taxoplasmosis' effects are often so minimial I don't think we'd call it a disease (otherwise 30%+ of the world has the disease).
> When microbes have been found in the human brain, they are associated with active infections or typically linked to a breakdown in the barrier due to diseases such as Alzheimer’s.
I think the question is whether there is a brain microbiome in healthy people, which seems to still be an open question.
The association in the article isn't a case of "we didn't find it in healthy people", but "we found it in more in unhealthy people".
From the article: "It found that, while there was a remarkable diversity of species in the control brains, there were often overgrowths of certain bugs in Alzheimer’s brains."
We know that non-brain microbiomes can influence behavior. What might something in brain tissue itself do?
They'll just be in low concentrations so they're hard to detect.
Absent that evidence, well biology is probability - something is always happening somewhere just by chance and statistics, but it doesn't make it a feature.
Your comment makes it sound like bacteria are harder to detect but if we’re already identifying viruses, locating bacteria seems easier.
(Though some viruses are bigger than the smallest bacteria, like Mycoplasma at 200nm, viruses are generally smaller)
At that point, 'just look with a good microscope' becomes infeasible, and you end up needing biological tricks like DNA amplification.
https://en.wikipedia.org/wiki/ToxoplasmosisIt's interesting to me that it would ever have been considered outlandish. In light of everything we now know about microbiomes and microbiology in general, it seems to me as a layman that the more radical proposition would be that the blood-brain barrier would be 100% effective at keeping out all bacteria, rather than the proposition that it probably isn't but that the bacteria it does let in tend to be symbiotic.
Bacteria is not usually found in most organs in the body though. Even more so in an organ as important as the brain that even our own immune system doesn't have access. The brain has its own cells to do that job. In order for bacteria to cross the blood brain barrier you need bacteria in the blood first, where they aren't normally found without getting under fire.
Having bacteria in the gut is more obvious and makes more sense.
Not saying it's impossible, just that the skepticism is warranted.
There is. The placenta and, oddly, prostate as well.
The microflora would need to have gotten there somehow, something analogous to endosymbiosis. But unless they're somehow getting from brain-to-egg-to-brain that's hard to explain. As for the others, they're easier, all being along the surfaces. Even the gut is on the "outside" in that membranes need not be crossed in order to access it.
Although counterpoint: the same argument would apply to a fish so I guess it's not impossible. Just more surprising.
Thus, both the spirochetes causing Lyme disease and those causing syphilis have high chances of reaching even the brain, while traveling through the body.
Fortunately, for the bacteria employing other means of locomotion it is usually more difficult to pass through many of the internal body tissues, as long as those are intact.
There are pathways from the outside to the brain - most notably the nose and the eyes. The former have a known pathogen pathway (naegleria fowleri, a virtually 100% fatal parasite), the latter are actually an immunoprivileged site [1] and investigations are ongoing what the role of eyes is in the transmission of H5N1 bird flu.
[1] https://www.aao.org/eye-health/tips-prevention/eye-immune-pr...
[2] https://www.unmc.edu/healthsecurity/transmission/2024/06/04/...
For the more internal organs, bacteria would have to travel across a skin of digestive tract barrier.
Unless they're present in the womb as the fetus starts growing, I guess.
I thought that was recently found to be false? Or at least it isn't the full picture. see for example: https://www.science.org/doi/10.1126/science.abo7649
At least one pathogen, Epstein-Barr virus, is known to inhabit B cells.
It probably has to do with the fact that, topologically speaking, the stomach (and the whole GI tract) is technically on the outside of our bodies.
Now, it could be the case that in a person with a compromised immune system AND a compromised blood brain barrier, that organisms would be able to live long enough to reach the brain. Once there, they would be mostly shielded from the immune system, except for brain glial cells (and I guess antibodies; usually the blood brain barrier stops most of them)
I guess this review/writeup https://asm.org/articles/2020/april/how-pathogens-penetrate-... covers most of the known mechanisms for traveral of the BBB by pathogens.
But why should this be taken a sign of a brain microbiome? I fail to see the connection you're implying.
>>> Yes, fish brains have a blood-brain barrier (BBB)
Anyway there's a pdf here that probably tells what kind of a BBB zebrafish have.
https://www.mdpi.com/1422-0067/22/22/12111
And the article itself says "... communities of bacteria thriving in salmon and trout brains. Many of the microbial species have special adaptations that allow them to survive in brain tissue, as well as techniques to cross the protective blood-brain barrier."
Not so long ago we thought fish or even human babies didn't feel pain, we take a lot of things for granted. https://hms.harvard.edu/news/long-life-early-pain
I STRONGLY believe there is a substantial central nervous system microbiome, but (spoiler alert) no evidence found in that search :)
If you're excited about this work, the datasets are all freely available from BossDB [2] — well over a dozen petavoxels of it! I'd be so curious if models these days could pick up on something we missed!
[1]: https://www.biorxiv.org/content/10.1101/2022.07.12.499807v1 [2]: https://bossdb.org
What gave you reason to believe this if you found no evidence of it in your own search?
If I said "I STRONGLY believe that a teapot is out there," it would be reasonable to ask me why.
Evidence is a thing that you claim could be part of an valid argument that something happened ("is consistent with"). This isn't a universal definition, but there's got to be some separation between proof and evidence. When there's evidence admitted into a court case, it doesn't necessarily mean that someone is guilty. When there's a lot of evidence and still no proof, you can and should (and will) still make a probabilistic case that something did happen.
So I'd agree with and disagree with you. There's no evidence (that you know of) that Russell's Teapot is there, which is why you do not believe it is there. If somebody does believe it is there, but admits that they have no proof that it is there, it would be reasonable to ask what evidence makes them believe that it is there.
Where I obviously agree with is that "belief" can't mean just something you want to think for no particular reason. Or if it does, it's certainly not worth talking about.
That is, we believe, very strongly, that it's impossible for two masses to repel each other gravitationally, for example, but we will never have actual proof it's impossible.
None of this to say that it's irrational to believe in a brain microbiome despite this search seeming fruitless, as there are good a priori arguments for expecting one to exist.
Exactly. Like the apocryphal small chocolate teapot orbiting the Earth
For the last 400 years, pathologists on every country had filleted and put, lets say tens thousands of human brains and human guts under the microscope. One of them has systematically a microbiome, easy to see. The other don't, except when is diseased or rotten. The sample token here is huge, maybe millions.
If we would had searched 400 years for this chocolate teapot without finding it, we could conclude with a solid suspicion that there is not such thing.
This is very different than just saying "I don't think that there is bacteria in the brain but I never searched for it". All pathology science is based in searching for it. We created gram staining dyes, scanners, tags, gold coated plates for electronic microscopes, DNA analysis... exactly for that.
If there really is a microbiome living in each healthy brain, we should have found it 150 years ago.
Is that really the case? By my understanding of the article, we find plenty of bacteria whenever we look at human brain samples. The problem is that it's very hard to tell if that bacteria was already present in the brain, or if it got in through the process of cutting the brain open (especially by contamination with other tissues), or if it was indeed present before the procedure, but only because the individual was very old or had a disease.
The chocolate teapot example is a non sequiter as it fails both Occam’s razor and the principle that extraordinary claims require extraordinary evidence not to mention that it wouldn’t follow any laws of known science and it’s existence very well would upend quite a few of those. The scientific method isn’t something you get to apply piecemeal.
We're lucky to live in a scientific era during which a "gut microbiome" is taken for granted (heck, even FDA-approved treatments depend on it! Google FMT, but don't click "images" from your work laptop), but it wasn't so long ago that we felt microbes were unlikely to live endogenously and harmlessly anywhere in the body.
There were also some hypotheses (untested, if memory serves) that COVID-19 influenced olfactory neurons through direct infection. Don't tell the blood-brain barrier, but if I were a bacterium, the nasal palate would be my ingress strategy. Or maybe the gums or gut — one of the cranial nerves, certainly. [edit] I should clarify — covid is viral, not bacterial, but it does show that this is a potential entry vector.
The central nervous system is incredibly complicated, and our symbiotic relationship with microbes is extraordinary. I think it does a disservice to bacteria to suppose they DON'T get involved in an organ :)
[1] https://www.space.com/ryugu-asteroid-sample-earth-life-colon...
The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria https://pubmed.ncbi.nlm.nih.gov/18806221/
Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis https://gut.bmj.com/content/63/2/281
So I think without trillions of bacteria to exclude, in the absence of any other issues excluding bacteria from the brain seems pretty doable.
Many viruses infect neurons, but they are way smaller than bacteria.
More nitpickfully, one of the big things we care about is if the bacteria are living _harmlessly_ in the brain. i.e., site of microbes, and a lack of inflammation, will answer more than just "are there microbes around".
Related recent story about earth microbes colonizing what was hoped to be a pristine sample of astroid captured in space: https://www.space.com/ryugu-asteroid-sample-earth-life-colon...
[0]: I already mentioned Adam Savage's excellent podcast with him elsewhere in this dicussion but here's a direct link: https://m.youtube.com/watch?v=MzzD2F73iGU&t=2s&pp=2AECkAIB
Given the ease of contamination of tissues (and databases), I tend to be pretty skeptical of tumor microbiome claims -- especially the wide-ranging claims of microbes being present in all tumors.
I would bet that your search was interesting, and that eventually you will find something.
Mikelson-Morely went looking for ether, and Einstein found relitivity.
Thank you for your work.
Despite only finding a single dime, that sounds fascinating. Can you say more?
The thin membrane discovered, again, just last year, is called the Subarachnoid Lymphatic-like Membrane (SLYM), and apparently acts as a protective barrier separating "clean" and "dirty" cerebrospinal fluid among potentially other things.
We don't know a lot.
Amoeba can get in via the nose from contaminated water.
https://en.wikipedia.org/wiki/Naegleriasis
You really don’t want that happening because they’ll literally eat your brain.
> I mentioned Adam Savage's "Scariest [Podcast] Episode Yet" in a different context the other day[0] in which I remember Joe DeRisi[1] saying something along the lines of brain & spinal fluid being "absolutely pristine" when it comes to the presence/absence of a microbiome (in healthy individuals) and that it'd be real problem if there were one.
> I'm just a layman but can anyone ELI5 how this can be squared with the OP, specifically with statements like
> > It turns out our grey matter is teeming with bacteria, viruses and fungi
Can anyone explain this?
https://www.newscientist.com/article/mg26335104-500-the-brai...
Parasites can live there. I think, Toxoplasma gondii and malaria and a brain eating ameba exists. If you planted a bean in the brain of a beagle, it would grow too. Though I hope we don't ever do that.
But what I mean is, what are the downstream consequences of this knowledge? Does it change how we can reason about health, cognition, etc?
Then this would hardly count as brain "microbiome".
Do wolves have a macrobiome of deer inside wolves guts?.
I think if it was extracellular we would see it more often in CSF - which is collected quite a bit in healthcare. Regular histology/pathology slices and staining would detect as well.
I could imagine an intracellular commensal bacteria that is small and virtually indistinguishable from an organelle like a mitochondria or lysosome that may exist.
Mitochondria were already bacteria at one point. Could there be another endosymbiont?
Mitochondria have circular DNA and phage like polymerase. Perhaps our secret symbiont can be found through DNA studies.
Examples of intracellular bacterial pathogens include: Brucella abortus Listeria spp. Chlamydia spp. Rickettsia spp. Ehrlichia spp. Anaplasma spp. Coxiella spp. Mycobacterium tuberculosis Salmonella spp.