A Lively Mind
December 3, 2024 6:43 AM Subscribe
...I honestly didn't know that we didn't know. I've long assumed this was a thing, of course it's a thing. Fascinating to find out it's only just now becoming a thing!
posted by Lyn Never at 7:21 AM on December 3, 2024
posted by Lyn Never at 7:21 AM on December 3, 2024
I'm picturing grocery stores carrying a probiotic brain-bacteria yoghurt smoothie that you can buy to cure your family members' conspiracy-fantacism, or other maladaptive political brain cooties.
posted by mrjohnmuller at 7:30 AM on December 3, 2024 [6 favorites]
posted by mrjohnmuller at 7:30 AM on December 3, 2024 [6 favorites]
It's just colonies, all the way down.
posted by mhoye at 7:35 AM on December 3, 2024 [6 favorites]
posted by mhoye at 7:35 AM on December 3, 2024 [6 favorites]
I fully agree with this quote from the article:
"While fish physiology is, in many ways, similar to humans’, there are some key differences."posted by moonmilk at 7:55 AM on December 3, 2024 [18 favorites]
Here, let me betray a certain ignorance and ask: If they want to know if we've got bacteria living in our brains, why not just...look? We do brain biopsies all the time. Spare a bit of tissue and poke around.
My larger fear with this is that it will turn out that, much like with gut microbiome, in theory you should be able to do fun things with it that make your life better, but in reality there will always be something (stomach acid, blood-brain barrier) that prevents you from manipulating your bacteria to do your bidding.
posted by mittens at 8:01 AM on December 3, 2024 [4 favorites]
My larger fear with this is that it will turn out that, much like with gut microbiome, in theory you should be able to do fun things with it that make your life better, but in reality there will always be something (stomach acid, blood-brain barrier) that prevents you from manipulating your bacteria to do your bidding.
posted by mittens at 8:01 AM on December 3, 2024 [4 favorites]
I imagine the reason we can't easily check for a brain microbiome is similar to why rabies tests on animals require euthenasia - it is almost intractably difficult to get sufficient access to fresh brain with a living subject.
posted by grumpybear69 at 8:03 AM on December 3, 2024
posted by grumpybear69 at 8:03 AM on December 3, 2024
"I'm picturing grocery stores carrying a probiotic brain-bacteria yoghurt smoothie that you can buy to cure your family members' conspiracy-fantacism, or other maladaptive political brain cooties."
I'm picturing a sf story-- either dystopian or exuberant cyberpunk-- about a society where competing groups are deploying belief-affecting brain infections.
posted by Nancy Lebovitz at 8:21 AM on December 3, 2024 [8 favorites]
I'm picturing a sf story-- either dystopian or exuberant cyberpunk-- about a society where competing groups are deploying belief-affecting brain infections.
posted by Nancy Lebovitz at 8:21 AM on December 3, 2024 [8 favorites]
This made me think of the placental microbiome kefuffle -- some scientists "discovered" a placental microbiome, but it turned out it was likely entirely down to contamination (sometimes from vaginal deliveries, sometimes just from the buffers/reagents since low biomass made it easier to amplify contaminant bacteria). Now when doing various kinds of microbiome genomics and metagenomics, it's expected that you'll carry a set of plain reagents through the whole sequencing process as well, so you can remove whatever populations get sequenced from the plain reagents from your results.
But it looks like the researchers in this one did have controls, and also some interesting negative results.
"No bacteria were recovered from CSF samples using culturomics (Fig. 1D), and no polymerase chain reaction (PCR) product could be amplified using 16S rDNA specific primers (fig. S2J)" -- so they're analyzing the cerebrospinal fluid separately and not finding any live bacteria in it (culturing) and also not finding any bacterial DNA which could be from live or dead bugs (amplifying DNA with PCR).
"Similarly, we recovered no colonies in the plates seeded with lysis buffer only as a negative control (Fig. 1D)." -- good, they're culturing their buffer too, to ensure it's not contaminated.
"Bacterial isolates were identified by 16S amplicon PCR using Sanger sequencing. A total of 54 isolates were recovered from different trout brain regions and different animals (table S1) and 120 isolates were obtained from all tissues sampled." - 16S rDNA primers are little bits of DNA code that is typically very similar in all bacteria, that also bracket a faster-evolving area of DNA that varies by organism. You can use these 16S primers to amplify that more unique DNA region and use it like a "barcode" to identify specific bacteria. (I honestly would really prefer to see them performing the same PCR on empty reagents as well as a negative control, although I didn't read every word of the paper and so it's possible I missed it. Also, it sounds like maybe they're straight-up sequencing bacteria they individually cultured? Which would make the lack of a negative control make sense, since it's sequencing an individual colony rather than doing metagenomics on a tissue sample.)
"Representative examples of bacterial cultures from the healthy trout brain and other tissues are shown in Fig. 1D. A few colonies were recovered from the laboratory environment swabs (fig. S2, A and D) but their taxonomic identity did not match any of the fish-derived isolates (fig. S2, B and C). Together, all our rigorous controls confirmed that the recovered culturable bacteria from the trout brain were not environmental contaminants." Lab environmental swabs, also a good negative control, gold star.
"To support these findings, we performed an in vivo oral gavage experiment using an antibiotic cocktail for 7 days (Fig. 1H) and sampled the gut, spleen, blood, and different brain regions for culturomics experiments. Antibiotic treatment eliminated all CFUs from the blood, spleen, and gut, whereas a few bacterial colonies, all with similar morphology, could still be recovered from the gut (Fig. 1I and fig. S1E). These experiments further substantiate that trout brain bacteria are not the result of experimental contaminations or artifacts." I'm less familiar with this, but I think the idea is that if you treat the salmon with antibiotics, and then you culture the 4 brain regions (and spleen and blood) and get *nothing*... well, the antibiotics worked. (They just worked less well in the gut, which had more microbes to begin with.) I think it's a sort of salmon-based negative control to show that when you didn't use antibiotics and got *something* in the spleen/blood/ various brain regions, that *something* was legit.
Caveat: I only dabbled in molecular microbiology as a 3-year sabbatical from my regular job. Would love to hear other other analyses and opinions.
posted by cnidaria at 9:03 AM on December 3, 2024 [5 favorites]
But it looks like the researchers in this one did have controls, and also some interesting negative results.
"No bacteria were recovered from CSF samples using culturomics (Fig. 1D), and no polymerase chain reaction (PCR) product could be amplified using 16S rDNA specific primers (fig. S2J)" -- so they're analyzing the cerebrospinal fluid separately and not finding any live bacteria in it (culturing) and also not finding any bacterial DNA which could be from live or dead bugs (amplifying DNA with PCR).
"Similarly, we recovered no colonies in the plates seeded with lysis buffer only as a negative control (Fig. 1D)." -- good, they're culturing their buffer too, to ensure it's not contaminated.
"Bacterial isolates were identified by 16S amplicon PCR using Sanger sequencing. A total of 54 isolates were recovered from different trout brain regions and different animals (table S1) and 120 isolates were obtained from all tissues sampled." - 16S rDNA primers are little bits of DNA code that is typically very similar in all bacteria, that also bracket a faster-evolving area of DNA that varies by organism. You can use these 16S primers to amplify that more unique DNA region and use it like a "barcode" to identify specific bacteria. (I honestly would really prefer to see them performing the same PCR on empty reagents as well as a negative control, although I didn't read every word of the paper and so it's possible I missed it. Also, it sounds like maybe they're straight-up sequencing bacteria they individually cultured? Which would make the lack of a negative control make sense, since it's sequencing an individual colony rather than doing metagenomics on a tissue sample.)
"Representative examples of bacterial cultures from the healthy trout brain and other tissues are shown in Fig. 1D. A few colonies were recovered from the laboratory environment swabs (fig. S2, A and D) but their taxonomic identity did not match any of the fish-derived isolates (fig. S2, B and C). Together, all our rigorous controls confirmed that the recovered culturable bacteria from the trout brain were not environmental contaminants." Lab environmental swabs, also a good negative control, gold star.
"To support these findings, we performed an in vivo oral gavage experiment using an antibiotic cocktail for 7 days (Fig. 1H) and sampled the gut, spleen, blood, and different brain regions for culturomics experiments. Antibiotic treatment eliminated all CFUs from the blood, spleen, and gut, whereas a few bacterial colonies, all with similar morphology, could still be recovered from the gut (Fig. 1I and fig. S1E). These experiments further substantiate that trout brain bacteria are not the result of experimental contaminations or artifacts." I'm less familiar with this, but I think the idea is that if you treat the salmon with antibiotics, and then you culture the 4 brain regions (and spleen and blood) and get *nothing*... well, the antibiotics worked. (They just worked less well in the gut, which had more microbes to begin with.) I think it's a sort of salmon-based negative control to show that when you didn't use antibiotics and got *something* in the spleen/blood/ various brain regions, that *something* was legit.
Caveat: I only dabbled in molecular microbiology as a 3-year sabbatical from my regular job. Would love to hear other other analyses and opinions.
posted by cnidaria at 9:03 AM on December 3, 2024 [5 favorites]
Oh boy Nancy Lebovitz, have you read Brain Plague by Joan Slonczewski? If not, you're in for a treat!
posted by cnidaria at 9:05 AM on December 3, 2024 [2 favorites]
posted by cnidaria at 9:05 AM on December 3, 2024 [2 favorites]
Look I don't need a fancy scientist to tell me about my brain microbiome. It's just sloshing around in a mélange of jelly beans and box wine, and I've been dealing with it for like 40 years.
This is super interesting though, and to my uneducated intuition, seems likely to be true across the board. Maybe I just personally enjoy the idea that my identity and consciousness is informed by the entirety of my body, including a community of distinct critters native to its environment, rather than just the grey matter.
It's a cool perspective to take in your relationship to yourself. Certainly improved my self care when I started taking that approach, rather than considering my body a burden my brain just has to deal with.
posted by Phobos the Space Potato at 11:23 AM on December 3, 2024 [6 favorites]
This is super interesting though, and to my uneducated intuition, seems likely to be true across the board. Maybe I just personally enjoy the idea that my identity and consciousness is informed by the entirety of my body, including a community of distinct critters native to its environment, rather than just the grey matter.
It's a cool perspective to take in your relationship to yourself. Certainly improved my self care when I started taking that approach, rather than considering my body a burden my brain just has to deal with.
posted by Phobos the Space Potato at 11:23 AM on December 3, 2024 [6 favorites]
If they want to know if we've got bacteria living in our brains, why not just...look? We do brain biopsies all the time.
Actually, brain biopsies are rarely done. And there are many micro-organisms that are difficult-to-impossible to grow in a lab. There are unknown zillions of species that we've never identified.
posted by neuron at 1:27 PM on December 3, 2024 [5 favorites]
Actually, brain biopsies are rarely done. And there are many micro-organisms that are difficult-to-impossible to grow in a lab. There are unknown zillions of species that we've never identified.
posted by neuron at 1:27 PM on December 3, 2024 [5 favorites]
neuron's right -- that's the benefit of using metagenomics and molecular methods rather than culture-based methods, you can potentially sequence/identify bugs that we don't know how to culture yet.
posted by cnidaria at 1:55 PM on December 3, 2024 [2 favorites]
posted by cnidaria at 1:55 PM on December 3, 2024 [2 favorites]
Some scientists have weighed in: There is no human brain microbiome.
posted by CheeseDigestsAll at 7:07 AM on December 4, 2024 [1 favorite]
posted by CheeseDigestsAll at 7:07 AM on December 4, 2024 [1 favorite]
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posted by Art_Pot at 7:07 AM on December 3, 2024