This is so fascinating Eric! Particularly the gut to sperm axis. Sperm is clearly highly sensitive. The topic of my next substack is the potential for sperm as a biomarker, with clear links to genetic and metabolically mediated conditions
I am a scientist but not in the medical field (I turned to earth sciences). My training (and inclination- I am fascinated by cell biology) gives me just enough background to sorta/kinda follow these articles. I am also a 2-time Lyme disease survivor, and then came Covid... and long Covid. These articles are helping me to begin to grasp some of the processes that likely are at work in my body, especially the confusing state of my immune system.
Oddly, I see some similarities to the effects that environmental toxins have on living beings as well. My physicians believe that the environmental toxins we are exposed to continuously contribute to how the immune system responds to treatment and recovery. I have sometimes felt as if I am an experiment where n=1, and I think that many of us with chronic illness are pretty much in that position. What is exciting to me is that this work is finally revealing some of the factors that underlie the commonalities among various disorders with different labels that affect people worldwide, and help illuminate how they affect people in different ways.
Grateful both for the research being done. Grateful for the folks who add more information. And especially you, Eric, for bringing it to us in a comprehensible way. This kind of information is often a starting point for my discussions with my physicians (they are used to me).
If helpful - please note that, different from other GLP-1 agonists, exenatide does cross the BBB to a small extent (with a ratio of CSF vs. plasma concentration of about 2%). This might conceivably be of some relevance when interpreting the exenatide preprint.
Right, thanks Thomas. I think there's an overall sense that there's not enough direct GLP-1 brain access to align with the CNS findings to date, as Drucker highlighted, but good to know about exenatide.
Given the centrality of the vagus nerve in these circuits, what does that mean for the safety of "over the counter" vagus nerve stimulation devices (eg Nurosym)?
They would seem to be rather blunt instruments focused on one circuit (normally depression) but I find it hard to believe they are discriminatory enough to ONLY activate that circuit and not have spillover effects to the others.
Thanks for your reply. I'm more of a computer systems guy so I'm not an expert on nerve conduction, but the way I interpreted the article was that these different vagus circuits are carried via different nerve bundles within the vagus nerve (or in computer terms "the signal is carried on a different cable, even if they are running in the same conduit trunking"). So I can't see how any *external* stimulation can ever target a particular subset of nerve fibres without actually implanting a probe that only interfaces with that subset of nerve fibres. I can see how you can do it with the brain in things like TCMS because you're using a 3D array of transducers to create overlapping magnetic fields that reinforce or cancel out each other to create a particular field intensity at a particular 3D location, and that field needs to reach a certain intensity to activate or block nerve transmission, but I can't see how you can do this with a single transducer on 1 axis.
The role of the Cholinergic Anti-inflammatory Pathway (CAP) forms the basis of the concepts promoted by our team of clinical and biochemist collaborators. The role of the a7 nicotinic acetylcholine receptor as a universal molecular chaperone is championed by our lead molecular scientist Maryna Skok. Her review of these critical receptors forms the basis for treating COVID19 as well as certain issues of cognition in Alzheimer’s Disease. The role of the modulator hydroxyUREA is described in several publications and begs to be identified as a credible and readily available repurposed therapeutic intervention for COVID19 pathophysiologies.
Refs:
1. Universal nature of cholinergic regulation demonstrated with nicotinic acetylcholine receptors
3. Lykhmus O, Kalashnyk O, et al Hydroxyurea interaction with α7 nicotinic acetylcholine receptor can underlie its therapeutic efficacy upon COVID-19. J Neuroimmunol. 2023 Dec 15;385:578244. doi: 10.1016
4. The role of the a7neuroreceptors and possible role in PASC:
The role of α7 nicotinic acetylcholine receptors in post-acute sequelae of covid-19. Int J Biochem Cell Biol. 2024 Jan 11;168:106519
I am not a doctor or scientist -- what would you say is the takeaway for those of us who would like to learn how to make changes in our health with this information?
Stay tuned. The Columbia researchers formed a company to take advantage of this circuit for autoimmune disorders. Many other developments in the works.
Thank you for this peak into how the science is evolving... I would love to understand how this links to the Porges polyvagal theory and indigenous/ ancient wisdom relating to rhythm and vagal tone. Particularly interested in the sperm research, and how this might enhance our understanding of the transmission of inter-generational trauma (where the microbiome is disrupted by stress and this disruption transmits)
First, I look forward to receiving your fantastic emails each week, Eric.
With so much evolving and emerging data on gut Microbiome, do you have any thoughts on prebiotic and probiotics? I have looked around recommendations and don’t find many credible comments on them. I would like to begin them. Any recommendations?
Thanks so much for this. Amazing things are happening right now. Not five minutes before reading this piece, I had read this one about a study from Harvard scientists. The brain mapped like never before(one small sliver!).
I couldn't access that link, for some reason, nor Science, where it was first published. Here's a link that works and has both incredible images and some good discussion for the layperson. Keeping in mind that the bit of brain was removed from a person with intractible epilepsy and may not be representative of "normal" brain tissue, the article and images are still fascinating. https://www.popsci.com/science/see-the-most-detailed-map-of-human-brain-matter-ever-created/
Aye carumba sorry about that. I think it’s because I’ve a paid Boston Globe account. Yes, good point about the epileptic nature of the tissue. Thank you!
Amazing stuff. Clearly what happens in vagus doesn’t stay in vagus…
As a non-medical person, but was able to understand just enough to want a further explanation. Thank you for sharing information such as this with us.
This is so fascinating Eric! Particularly the gut to sperm axis. Sperm is clearly highly sensitive. The topic of my next substack is the potential for sperm as a biomarker, with clear links to genetic and metabolically mediated conditions
Agree Neel, thanks!
I am a scientist but not in the medical field (I turned to earth sciences). My training (and inclination- I am fascinated by cell biology) gives me just enough background to sorta/kinda follow these articles. I am also a 2-time Lyme disease survivor, and then came Covid... and long Covid. These articles are helping me to begin to grasp some of the processes that likely are at work in my body, especially the confusing state of my immune system.
Oddly, I see some similarities to the effects that environmental toxins have on living beings as well. My physicians believe that the environmental toxins we are exposed to continuously contribute to how the immune system responds to treatment and recovery. I have sometimes felt as if I am an experiment where n=1, and I think that many of us with chronic illness are pretty much in that position. What is exciting to me is that this work is finally revealing some of the factors that underlie the commonalities among various disorders with different labels that affect people worldwide, and help illuminate how they affect people in different ways.
Grateful both for the research being done. Grateful for the folks who add more information. And especially you, Eric, for bringing it to us in a comprehensible way. This kind of information is often a starting point for my discussions with my physicians (they are used to me).
Thank you!
The Vagus Nerve seems to have quite an impact on almost everything, are there dedicated Vagus specialties in medicine at present?
You're so right. A new podcast with the founder of a dysautonomia clinic is coming soon!
Wonderful, as always, Eric!
If helpful - please note that, different from other GLP-1 agonists, exenatide does cross the BBB to a small extent (with a ratio of CSF vs. plasma concentration of about 2%). This might conceivably be of some relevance when interpreting the exenatide preprint.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31585-4
Thank you so much for all you do!
Thomas
Right, thanks Thomas. I think there's an overall sense that there's not enough direct GLP-1 brain access to align with the CNS findings to date, as Drucker highlighted, but good to know about exenatide.
I heard a paper presented a few years ago in the connection between balance (cerebellum) and ADHD/executive function.
I’m a child psychiatrist.
Given the centrality of the vagus nerve in these circuits, what does that mean for the safety of "over the counter" vagus nerve stimulation devices (eg Nurosym)?
They would seem to be rather blunt instruments focused on one circuit (normally depression) but I find it hard to believe they are discriminatory enough to ONLY activate that circuit and not have spillover effects to the others.
Does this not raise concerns?
Yes, I wonder about that too. They're being marketed with scant data. Lots of potential but barely developed so far
Thanks for your reply. I'm more of a computer systems guy so I'm not an expert on nerve conduction, but the way I interpreted the article was that these different vagus circuits are carried via different nerve bundles within the vagus nerve (or in computer terms "the signal is carried on a different cable, even if they are running in the same conduit trunking"). So I can't see how any *external* stimulation can ever target a particular subset of nerve fibres without actually implanting a probe that only interfaces with that subset of nerve fibres. I can see how you can do it with the brain in things like TCMS because you're using a 3D array of transducers to create overlapping magnetic fields that reinforce or cancel out each other to create a particular field intensity at a particular 3D location, and that field needs to reach a certain intensity to activate or block nerve transmission, but I can't see how you can do this with a single transducer on 1 axis.
The role of the Cholinergic Anti-inflammatory Pathway (CAP) forms the basis of the concepts promoted by our team of clinical and biochemist collaborators. The role of the a7 nicotinic acetylcholine receptor as a universal molecular chaperone is championed by our lead molecular scientist Maryna Skok. Her review of these critical receptors forms the basis for treating COVID19 as well as certain issues of cognition in Alzheimer’s Disease. The role of the modulator hydroxyUREA is described in several publications and begs to be identified as a credible and readily available repurposed therapeutic intervention for COVID19 pathophysiologies.
Refs:
1. Universal nature of cholinergic regulation demonstrated with nicotinic acetylcholine receptors
Maryna Skok
https://doi.org/10.1016/j.bbadva.2022.100061
2. The most recent studies are described by our collaborators in this publication:
https://doi.org/10.1016/j.bbrc.2024.149825
3. Lykhmus O, Kalashnyk O, et al Hydroxyurea interaction with α7 nicotinic acetylcholine receptor can underlie its therapeutic efficacy upon COVID-19. J Neuroimmunol. 2023 Dec 15;385:578244. doi: 10.1016
4. The role of the a7neuroreceptors and possible role in PASC:
The role of α7 nicotinic acetylcholine receptors in post-acute sequelae of covid-19. Int J Biochem Cell Biol. 2024 Jan 11;168:106519
These articles and studies are all complementary.
I am not a doctor or scientist -- what would you say is the takeaway for those of us who would like to learn how to make changes in our health with this information?
The chance to controlling our immune system, blocking cancer spread, being in touch with father gut microbial potential transmission impact…….
Yes, I want those things. What do I do?
Stay tuned. The Columbia researchers formed a company to take advantage of this circuit for autoimmune disorders. Many other developments in the works.
Thank you for this peak into how the science is evolving... I would love to understand how this links to the Porges polyvagal theory and indigenous/ ancient wisdom relating to rhythm and vagal tone. Particularly interested in the sperm research, and how this might enhance our understanding of the transmission of inter-generational trauma (where the microbiome is disrupted by stress and this disruption transmits)
First, I look forward to receiving your fantastic emails each week, Eric.
With so much evolving and emerging data on gut Microbiome, do you have any thoughts on prebiotic and probiotics? I have looked around recommendations and don’t find many credible comments on them. I would like to begin them. Any recommendations?
Chris Thompson, MD
"high-fat diet promotes spread of cancer"🙉🙈
Am I reading this right that the gut to sperm axis is an instance of Lamarckian evolution?
Thanks so much for this. Amazing things are happening right now. Not five minutes before reading this piece, I had read this one about a study from Harvard scientists. The brain mapped like never before(one small sliver!).
https://www.bostonglobe.com/2024/05/10/metro/google-harvard-brain-map-images/
Agree, that's one more example of the extraordinary progress that's happening now. Thanks
I couldn't access that link, for some reason, nor Science, where it was first published. Here's a link that works and has both incredible images and some good discussion for the layperson. Keeping in mind that the bit of brain was removed from a person with intractible epilepsy and may not be representative of "normal" brain tissue, the article and images are still fascinating. https://www.popsci.com/science/see-the-most-detailed-map-of-human-brain-matter-ever-created/
Aye carumba sorry about that. I think it’s because I’ve a paid Boston Globe account. Yes, good point about the epileptic nature of the tissue. Thank you!