[HN Gopher] Fish have a brain microbiome - could humans have one...
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       Fish have a brain microbiome - could humans have one too?
        
       Author : rbanffy
       Score  : 322 points
       Date   : 2024-12-02 18:20 UTC (1 days ago)
        
 (HTM) web link (www.quantamagazine.org)
 (TXT) w3m dump (www.quantamagazine.org)
        
       | cbsmith wrote:
       | Short answer: yes.
       | 
       | https://www.theguardian.com/lifeandstyle/2024/dec/01/the-bra...
        
         | ch4s3 wrote:
         | Let's not jump to conclusions. That guardian article is about a
         | pre-print study that used frozen brain samples from a single
         | tissue bank, and RNA sequencing was done on a single machine.
         | 
         | 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...
        
           | cbsmith wrote:
           | Contamination is possible, but it's hard to explain the
           | results that way. Definitely needs replication, of course.
           | 
           | 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).
        
         | outworlder wrote:
         | That doesn't seem to be that clear cut.
         | 
         | 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.
        
           | cbsmith wrote:
           | > Evidence is scarce and the article is talking about brains
           | with active illnesses.
           | 
           | 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).
        
         | Aloisius wrote:
         | From the article:
         | 
         |  _> 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.
        
           | cbsmith wrote:
           | I mean, we know about all kinds of microbes that can be in
           | the brains of "unhealthy" people, and we've known that for
           | ages (taxoplasmosis and CJD come to mind).
           | 
           | 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."
        
         | CatWChainsaw wrote:
         | Biology and binary do not play nice.
        
       | _tom_ wrote:
       | Wow. If true, that would be fascinating.
       | 
       | We know that non-brain microbiomes can influence behavior. What
       | might something in brain tissue itself do?
        
         | debacle wrote:
         | Influence behavior.
        
           | ertgbnm wrote:
           | Somehow the brain microbiome is only able to influence the
           | gut.
        
             | layer8 wrote:
             | My gut tells me that the gut influences behavior.
        
           | krackers wrote:
           | You can look at toxoplasmosis as an example, synthesizes
           | dopamine and is somehow able to selectively modulate
           | attraction to predators.
        
       | londons_explore wrote:
       | Pretty sure all parts of our bodies are riddled with viruses and
       | fungi, and maybe bacteria too if we look hard enough.
       | 
       | They'll just be in low concentrations so they're hard to detect.
        
         | devops99 wrote:
         | Look up "Cosmic Death Fungus", there is some (but only some..)
         | truth there.
        
         | XorNot wrote:
         | That rather speaks against it being a microbiome - it could
         | just be incidental contamination the body is in the process of
         | cleaning up. To be a microbiome I would expect to a diverse,
         | well-adapted quorum of species that find some type of
         | symbioses.
         | 
         | 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.
        
         | biofunsf wrote:
         | Aren't viruses much harder to detect than bacteria? Viruses are
         | generally smaller and are completely inert without a host cell.
         | Bacteria, besides be larger, also have their own metabolic
         | processes and distinct structures you can do things like grow
         | them in a laboratory culture until the colony is much obvious.
         | 
         | 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)
        
           | londons_explore wrote:
           | Both are hard to detect if there are only hundreds of them
           | amongst trillions of human cells.
           | 
           | At that point, 'just look with a good microscope' becomes
           | infeasible, and you end up needing biological tricks like DNA
           | amplification.
        
         | eleveriven wrote:
         | And it makes me wonder how much we're still missing or
         | overlooking in the microbial landscape of our own bodies.
        
       | devops99 wrote:
       | Some do and it has a huge impact on human behavior.
       | https://en.wikipedia.org/wiki/Toxoplasmosis
        
         | velcrovan wrote:
         | In case it helps others: to find out what the above comment's
         | "huge impact on human behavior" is supposed to refer to, you'll
         | need to dig into references/footnotes #23, #25, #27, #28 and
         | #29 on the linked Wikipedia entry.
        
       | lolinder wrote:
       | > Matthew Olm (opens a new tab), a physiologist who studies the
       | human microbiome at the University of Colorado, Boulder and was
       | not involved with the study, is "inherently skeptical" of the
       | idea that populations of microbes could live in the brain, he
       | said. But he found the new research convincing. "This is concrete
       | evidence that brain microbiomes do exist in vertebrates," he
       | said. "And so the idea that humans have a brain microbiome is not
       | outlandish."
       | 
       | It'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.
        
         | outworlder wrote:
         | > 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,
         | 
         | 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.
        
           | lolinder wrote:
           | The lungs, mammary glands, uterus, ovaries, vagina, placenta,
           | semen, eyes, skin, and nasal cavity all have their own
           | documented microbiome so far, and we've been finding out
           | about new microbiomes about once a year. They are not a thing
           | that is reserved for the digestive tract.
        
             | outworlder wrote:
             | The brain is _unusually_ protected though. There's nothing
             | like the blood brain barrier basically anywhere else. Most
             | the the tissues you mentioned are exposed to the
             | environment in some way. There aren't many ways to reach
             | the brain without getting inside the body first(sensory
             | organs being the obvious pathway, but even that is a
             | stretch).
             | 
             | Not saying it's impossible, just that the skepticism is
             | warranted.
        
               | forgotoldacc wrote:
               | > There's nothing like the blood brain barrier basically
               | anywhere else.
               | 
               | There is. The placenta and, oddly, prostate as well.
        
             | __MatrixMan__ wrote:
             | If you were to simplify the human body to a sphere (or
             | torus... or whatever corresponds with the number of
             | orifices that a human has), then all of the microbiomes
             | you've listed would be on the exterior. The brain (and
             | heart and kidneys and liver and bones and...) would not be.
             | 
             | 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.
        
               | Wilsoniumite wrote:
               | I think it depends a bit on how you count but I've heard
               | it is an 8 holed donut
        
               | __MatrixMan__ wrote:
               | It also differs between individuals (e.g. one can develop
               | a fistula).
        
               | eru wrote:
               | Or get a piercing.
        
               | InDubioProRubio wrote:
               | So getting pierced, puts one topological outside of
               | baseline humanity?
        
               | __MatrixMan__ wrote:
               | I suppose it does. Be careful, you wouldn't want to end
               | up homeomorphic to the wrong crowd.
        
               | moi2388 wrote:
               | Aren't tattoos injective?
        
               | worksonmymach wrote:
               | If I met a 8 holed donut I'd tear it a new one.
        
               | __MatrixMan__ wrote:
               | I expect I'd start by tearing it one fewer: now a seven
               | holed donut with some stubs.
        
               | 725686 wrote:
               | Michael Stevens of VSauce fame has you covered with his
               | "How Many Holes Does a Human Have?" video:
               | 
               | https://www.youtube.com/watch?v=egEraZP9yXQ
        
               | tmnvix wrote:
               | Thanks for mentioning this. I really enjoyed the video
               | and learned a thing or two. Would recommend!
        
               | weberer wrote:
               | We already know of harmful pathogens that can infect the
               | brain, such as Borreliosis. The only jump now is the fact
               | that there could also exist harmless bacteria.
               | 
               | https://pmc.ncbi.nlm.nih.gov/articles/PMC8232152/
        
               | adrian_b wrote:
               | Spirochetes are much more efficient than most bacteria at
               | moving through very viscous media, which include the
               | obstacles encountered when moving through an animal body.
               | 
               | 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.
        
               | mschuster91 wrote:
               | > But unless they're somehow getting from brain-to-egg-
               | to-brain that's hard to explain.
               | 
               | 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/...
        
             | BurningFrog wrote:
             | Those are all organs that are directly exposed to outside
             | materials.
             | 
             | 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.
        
               | askvictor wrote:
               | Indeed, those organs expose to the outside world have
               | reason to cultivate friendly bacteria for no other reason
               | than to take up space, to stop hostile bacteria having a
               | place to take hold.
        
           | __MatrixMan__ wrote:
           | Agreed. Additionally, one of the mechanisms keeping the gut
           | bacteria from taking over the rest of the body is an oxygen
           | gradient: anaerobic bacteria in the gut are unlikely to be
           | interested in an exploration of the aerobic environment of
           | the body. Oxygen diffuses freely across the blood brain
           | barrier, so it would not serve as an analogous containment
           | mechanism.
        
           | 20after4 wrote:
           | > even our own immune system doesn't have access
           | 
           | 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
        
             | s1artibartfast wrote:
             | It is certainly true as a rule of thumb, although there may
             | be more going on locally that was previously thought
        
           | panabee wrote:
           | This is unrelated to your main point, more to clarify an edge
           | case for those interested in learning more: B cells can
           | breach the BBB under certain conditions.
           | 
           | At least one pathogen, Epstein-Barr virus, is known to
           | inhabit B cells.
        
           | ghurtado wrote:
           | > Having bacteria in the gut is more obvious and makes more
           | sense.
           | 
           | 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.
        
           | eleveriven wrote:
           | But bacteria are incredibly adaptable
        
         | njtransit wrote:
         | Is it the blood brain barrier that keeps out bacteria or your
         | immune system? Admittedly I know little about biology, but I
         | thought bacteria growing inside your body was generally
         | considered a "bad thing" (topologically speaking, your
         | digestive system is outside your body).
        
           | outworlder wrote:
           | Indeed. In order to even try to cross the blood brain
           | barrier, an organism would have to be in the blood already.
           | If that's unexpected, the immune system certainly won't like
           | it. Large compounds and even immune cells aren't supposed to
           | cross it. Usually brain infections are from tiny viruses
           | because of that, unless they found another way (like ear,
           | nose or eye infections, all of them effectively brain
           | 'appendages').
           | 
           | 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)
        
         | dekhn wrote:
         | From what I understand about the BBB, it's practically
         | impermeable to anything the size of a bacteria (mainly intended
         | for gating small molecules like fats and drugs), until an
         | individual has some sort of disease or other health problem
         | that effects the BBB's integrity. But I can easily imagine that
         | some bacteria (harmful, or helpful) could have exactly the
         | right surface proteins to indicate it's permitted.
         | 
         | 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.
        
         | tomcam wrote:
         | I am skeptical that the brain wouldn't have a microbiome
        
           | throwawaymaths wrote:
           | There are regions of the body that almost certainly do not
           | have a microbiome, for example the viteous humor
        
             | tomcam wrote:
             | I'm talking about the brain in particular. A lot goes on
             | and it consumes a ton of resources.
        
               | F-Lexx wrote:
               | > A lot goes on and it consumes a ton of resources.
               | 
               | But why should this be taken a sign of a brain
               | microbiome? I fail to see the connection you're implying.
        
         | seizethecheese wrote:
         | A start: do fish have a blood brain barrier that's similar to
         | humans?
        
           | fasteo wrote:
           | This is indeed the first question to ask. According to
           | ChatGpt (don't beat me up)
           | 
           | >>> Yes, fish brains have a blood-brain barrier (BBB)
        
             | card_zero wrote:
             | You can't just say "don't beat me up" and expect not to be
             | beaten up.
             | 
             | 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."
        
               | fasteo wrote:
               | ha, I guess you are right
               | 
               | https://en.wikipedia.org/wiki/Self-fulfilling_prophecy
        
         | glfharris wrote:
         | CSF sampling is a routine investigation in most hospitals. We
         | don't typically see bacteria in these samples, when we do, its
         | in the form of bacterial meningitis, hence the skepticism.
        
         | biofunsf wrote:
         | When something seems obvious to me but scientists in the field
         | disagree, I usually take this a sign I need to improve my own
         | understanding.
        
           | lolinder wrote:
           | Unfortunately as often as not this doesn't seem to be the
           | case. Expertise in a field often seems to create blinders.
        
         | eleveriven wrote:
         | And I think the brain, like other organs, might have its own
         | microbial community, even if it's a small or specialized one.
        
         | sumitkumar wrote:
         | I like to think that the bacteria are only on the outermost
         | layer of the body, i.e. skin. It just happens so that the
         | respiratory and the digestive systems are the exterior part of
         | the body which are inside our body. In other words epithelial
         | cells mark the boundary of inside and outside and bacteria are
         | usually tolerated on the outside and not inside.
        
         | dr_dshiv wrote:
         | So, what does that say about the possibility of fungal
         | symbiotes?
        
         | lm28469 wrote:
         | > It's interesting to me that it would ever have been
         | considered outlandish
         | 
         | 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
        
       | j6m8 wrote:
       | A few years ago my team mounted what I think was the largest-(to-
       | date) scale search for this in electron microscopy brain tissue
       | volumes [1].
       | 
       | 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
        
         | outworlder wrote:
         | Since I don't have enough information on the topic... how would
         | one distinguish a microbiome that was present while the
         | organism was alive, from contamination after death?
        
           | j6m8 wrote:
           | That's a question more suited to a microbiologist or
           | bacteriologist than to me, but my educated guess, at least in
           | the electron microscopy case, is that you'll see the bacteria
           | inside the depth of the slices, rather than sitting "atop"
           | the slices. i.e., if you cut open an apple and find half a
           | worm, the worm was in the apple. If you cut open an apple and
           | then see a worm on top of the slice, it's possible it arrived
           | post-cut.
        
         | lovich wrote:
         | > I STRONGLY believe there is a substantial central nervous
         | system microbiome, but (spoiler alert) no evidence found in
         | that search :)
         | 
         | What gave you reason to believe this if you found no evidence
         | of it in your own search?
        
           | attemptone wrote:
           | This might be too nitpicky, but isn't believe exactly what
           | one has in absence of evidence?
        
             | SamBam wrote:
             | They're is no evidence that Russell's Teapot is floating
             | out in space in orbit around the sun, AND I don't believe
             | that it's there.
             | 
             | If I said "I STRONGLY believe that a teapot is out there,"
             | it would be reasonable to ask me why.
        
               | pessimizer wrote:
               | Also (and this is a pet peeve of mine), we're talking
               | about _evidence_ not _proof_. They 're not the same
               | thing. Just because there's evidence that something
               | happened, it doesn't mean that it happened.
               | 
               | 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.
        
           | vlovich123 wrote:
           | Absence of proof is not proof of absence. I would imagine
           | that it would take a lot of negative searches by many people
           | trying different approaches to rule it out. The searches are
           | likely to be carried out by people who believe in the idea
           | rather than those that are skeptical they will find something
           | (the skeptics will work on reproducing any positive results).
        
             | tsimionescu wrote:
             | It should be noted that absence of proof _is_ evidence for
             | absence. And since in the physical sciences, unlike
             | mathematics, actual proof of absence is impossible, absence
             | of evidence (after thorough searches) is the best we 've
             | got to form a belief for absence of the phenomenon.
             | 
             | 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.
        
               | KineticLensman wrote:
               | > It should be noted that absence of proof is evidence
               | for absence.
               | 
               | Exactly. Like the apocryphal small chocolate teapot
               | orbiting the Earth
        
               | pvaldes wrote:
               | But evidence of absence is, and in this case we have a
               | lot.
               | 
               | 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.
        
               | tsimionescu wrote:
               | > 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.
               | 
               | 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.
        
               | vlovich123 wrote:
               | Yeah exactly. It's not an unreasonable search and we
               | don't have confidence our search methods work. Hell, the
               | Ryugu sample was contaminated while in a hermetically
               | sealed clean room filled with nitrogen gas. Either the
               | blood brain barrier is even more effective or maybe the
               | story isn't quite so clear. This is not an unreasonable
               | hypothesis nor do have we exhausted search. Hell, we're
               | literally talking about it in response to a related find
               | in another species. So it's definitely not a wild theory
               | or one that conflicts with known theories.
               | 
               | 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.
        
               | rapjr9 wrote:
               | Unfortunately many people claim an absence of evidence
               | _without_a_thorough_search_ is evidence of absence. As in
               | "I have haven't seen it so it must not exist". Many
               | people who are experts do this. There needs to be some
               | new terminology here, just saying "there is no evidence"
               | is meaningless, people need to start saying "there is no
               | evidence after <these> kinds of searches" to qualify
               | their statements. Like "I haven't seen any evidence, but
               | I haven't really looked", or "I asked some of my
               | collegues and none had seen any relevant papers", or "I
               | did a PubMed search and found no papers on that topic",
               | or "I did a PubMed search and found 10 low quality
               | studies that showed no evidence of that". Otherwise it is
               | completely reasonable to interpret "there is no evidence"
               | as "I don't know".
        
           | j6m8 wrote:
           | Microbes are CRAZY. They're everywhere. Thermal vent-friendly
           | microbes. Space-friendly microbes. Vacuum-resilient, heat-
           | resilient, acid-resilient. Microbe-free-environment-friendly
           | microbes [1]. It seems hard to imagine that a blood-brain
           | barrier could really keep the brain sterile.
           | 
           | 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...
        
             | pazimzadeh wrote:
             | Our defenses are also crazy. For example, the inner mucus
             | layer of the colon is able to keep trillions of bacteria at
             | bay the vast majority of the time (unless there is
             | inflammation or takeover by specific mucus-eating
             | bacteria). Many of the proteins in the secreted mucus
             | layers are still unknown in function, like FCGBP which
             | comprises up to 40% of the protein content of mucus.
             | 
             | 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.
        
         | flir wrote:
         | I know nothing about this, so I guess I'm asking "why can't we
         | do this?": take some brain, throw it in a blender, and look for
         | DNA the same way the ancient environmental DNA people do?
        
           | j6m8 wrote:
           | Very hard to clean a blender!
           | 
           | 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".
        
           | dhosek wrote:
           | You'd have to get that brain cleanly from the creature to the
           | blender.
        
           | bagels wrote:
           | You can't find out this way. Removing brains exposes it to an
           | outside environment where there are microbes. You can't tell
           | if they arrived before or after you removed the material.
           | 
           | 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...
        
             | flawn wrote:
             | Maybe the first point you make is also the argument for why
             | our brain might have a microbiome, as our body is not in
             | any way hermetically enclosed, and e.g. amoebas are able to
             | infect our brains just by going through our nose.
        
           | codethief wrote:
           | From what I understand Joe DeRisi's approach[0] comes
           | relatively close to your "blender" idea!
           | 
           | [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
        
         | stenl wrote:
         | Cool! Has anything similar been attempted in tumor tissue,
         | given the many claims of microbes in tumors? Especially tumors
         | not in contact with the exterior.
        
           | mbreese wrote:
           | As far as I know, most of the tumor microbiome claims haven't
           | held up very well. For example, the 2020 Nature paper
           | "Microbiome analyses of blood and tissues suggest cancer
           | diagnostic approach" was retracted this past year [1].
           | 
           | 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.
           | 
           | [1] https://www.nature.com/articles/s41586-024-07656-x
        
         | ForOldHack wrote:
         | I once saw a video about using a scanning tunneling microscope.
         | I wanted to get a handle on how hard it was, so I scanned an
         | area the size of 4 football fields and found a single dime. It
         | takes a long time just to figure out what you are looking for.
         | We have literally not even scratched the surface.
         | 
         | 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.
        
           | fragmede wrote:
           | > I scanned an area the size of 4 football fields and found a
           | single dime.
           | 
           | Despite only finding a single dime, that sounds fascinating.
           | Can you say more?
        
         | biofunsf wrote:
         | What makes a hypothetical brain microbiome so hard to find? I
         | would think that once you're doing microscopy on brain slices
         | that a biome would show you quite fast. But if you're still
         | optimistic after a negative search I assume there must be many
         | reasons why a brain microbiome could exist but still be hard to
         | detect.
        
       | vasan wrote:
       | Gut microbes affect brain too
        
       | andai wrote:
       | I recall reading about this 1 or 2 years ago! But I don't
       | remember details. Has there perhaps been tentative evidence?
        
       | b800h wrote:
       | If this were to be the case in humans, I wonder what effect
       | antibiotics would be having on behaviour.
        
         | PartiallyTyped wrote:
         | and conversely whether probiotics for the brain might exist.
        
           | singlow wrote:
           | Countdown until the nutrition influencers start pushing them.
        
         | AlfredBarnes wrote:
         | How much of the thinking/feeling would be due to this
         | microbiome? Is this how people develop mental illnesses? Such
         | an interesting topic! I hope it gets the funding it needs!
        
       | sethammons wrote:
       | I was very surprised that just last year, 2023, we discovered a
       | whole ass thin membrane covering the brain we didn't know was
       | there.
       | 
       | 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.
        
         | hirenj wrote:
         | On this topic, you might be interested in this article and the
         | related discussion regarding novel anatomy.
         | 
         | https://news.ycombinator.com/item?id=41517059
        
         | eleveriven wrote:
         | Just how much we still don't know about the brain and its
         | protective systems... It's crazy to think that a major part of
         | the brain's anatomy was essentially hiding in plain sight for
         | all these years.
        
       | AvAn12 wrote:
       | Aren't there some kinds of amoeba that can cross the BBB and take
       | up residence in the brain? And fungal infections? (Or am I just
       | thinking of horror movie plots?)
        
         | lamename wrote:
         | The one I know of is terrifying and usually lethal. It gets in
         | through the nose/cribriform plate
         | https://en.wikipedia.org/wiki/Naegleria_fowleri
        
         | mr_toad wrote:
         | It's rare, but viruses, bacteria, fungi, amoeba, worms and
         | other parasites can get into the brain and cause meningitis.
         | 
         | 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.
        
       | codethief wrote:
       | Two months ago we had almost the same topic here on HN and I
       | posted a question that no one seemed to be able to answer:
       | 
       | > 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?
       | 
       | [0] https://news.ycombinator.com/item?id=41765112
        
         | mmmrtl wrote:
         | Probably the vast majority of studies are correct and a few
         | misinterpret artefacts, and then a journalist uses an evocative
         | word like "teeming" without knowing that what they're saying
         | doesn't pass the sniff test. Same reason these papers languish
         | for years and don't pass peer review in rigorous journals
        
       | nborwankar wrote:
       | Not sure if this article provides enough definitive info -
       | happened to see it yesterday.
       | 
       | https://www.newscientist.com/article/mg26335104-500-the-brai...
        
       | dukeofdoom wrote:
       | Most people will read this headline as a question. I read it like
       | a proposition for bio weapon lab research. Post covid.
       | 
       | 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.
        
       | jexe wrote:
       | If this were also true for humans, what would the implications
       | be?
        
         | unnouinceput wrote:
         | that a bacteria decided to "lemme make this dude ask a question
         | on HN". On a serious note, it's already answered in the article
         | - it means that our behavior is not only influenced by the gut
         | bacteria (already proven), but the brain ones too.
        
           | jexe wrote:
           | Well finally I have a new excuse to ask dumb questions
           | here...
           | 
           | But what I mean is, what are the downstream consequences of
           | this knowledge? Does it change how we can reason about
           | health, cognition, etc?
        
             | unnouinceput wrote:
             | unknown. they barely suspect this, to your question is
             | another leap in science for future generations of
             | researchers
        
       | Vaslo wrote:
       | What would this say about taking antibiotics? Would the blood-
       | brain barrier keep them out?
        
         | unnouinceput wrote:
         | no. they are molecules, and they are let in by the barrier.
        
           | biofunsf wrote:
           | It depends. Some antibiotics pass the BBB easier than others.
           | Some are used especially when passage through the BBB is
           | desired.
        
       | piombisallow wrote:
       | The whole microbiome thing is way overblown. It's like studying a
       | great city by looking at rats in the sewer. And yeah, maybe some
       | people have rats in their houses too. That's doesn't really tell
       | you much about the city.
        
       | amit9gupta wrote:
       | There has been some research on this, establishing the presence
       | of microbiome in the brain:
       | 
       | https://www.biorxiv.org/content/10.1101/2023.02.06.527297v1
        
         | mmmrtl wrote:
         | Why hasn't it passed peer review yet? Maybe because they only
         | used techniques prone to artefacts. IMO if a brain microbiome
         | exists in healthy people it would have been seen already, with
         | all the microscopy and sequencing done
        
       | eleveriven wrote:
       | Sooo our brain might not be sterile (frighteningly). And we might
       | see a shift in how we approach even mental health in the future.
        
       | pvaldes wrote:
       | > Is possible that the bacteria were swallowed by the white cells
       | 
       | Then this would hardly count as brain "microbiome".
       | 
       | Do wolves have a macrobiome of deer inside wolves guts?.
        
       | skirge wrote:
       | left-handed and right-handed bacteria determining political
       | beliefs
        
         | leptons wrote:
         | That would explain a lot of things that seem completely
         | baffling.
        
           | ttyprintk wrote:
           | Consider a worm attacking the judgment and inhibition center.
        
       | Pigalowda wrote:
       | I'm skeptical but there's plenty of intracellular bacterial
       | pathogens. Perhaps there's an intracellular commensal
       | bacteria/symbiote.
       | 
       | 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.
        
       | m0ose wrote:
       | Dr Salinas is awesome. She did an interview on "The Children's
       | Hours" about lung fish that was so interesting. Her fish research
       | is leading to a ton of human immunology understanding.
        
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