[j6m8]

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

[lovich]

> 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?

[j6m8]

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...

[vlovich123]

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).

[attemptone]

This might be too nitpicky, but isn't believe exactly what one has in absence of evidence?

[biofunsf]

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.

[ForOldHack]

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]

> 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?

[stenl]

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]

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

[flir]

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?

[bagels]

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...

[j6m8]

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]

You’d have to get that brain cleanly from the creature to the blender.

[codethief]

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

[outworlder]

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]

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.