[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  : 138 points
       Date   : 2024-12-02 18:20 UTC (4 hours 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...
        
         | 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.
        
         | 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.
        
       | _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.
        
           | 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.
        
       | 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.
        
             | __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).
        
             | 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.
        
         | 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.
        
       | 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
        
           | 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...
        
         | 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...
        
         | 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
        
       | 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.
        
       | 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
        
       | 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
        
       | 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
        
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