🧵 View Thread
🧵 Thread (98 tweets)
"In a quest for standardized and spotless mice, scientists have made the creatures a less-faithful model for human immune systems, which develop in a world teeming with microbes." [2018]https://t.co/8BPVujsgba https://t.co/RxUUCoCwRF
"yet another warning [that] lab mice are very imperfect predictors of results’ translation to humans. But there is a silver lining that, now, a better mouse model is available to confirm or refute promising results in traditional lab mice" [2019]https://t.co/hzArEte8BC
I think a lot about sexist mice. (Don't you?)I wonder if having wild-type microbes will impact this effect.https://t.co/SZc0yHQGfv
Ask me why I'm exploring zoning laws and legalities of housing large populations of wild-type mice in an underground complex.#dreambigdreamshttps://t.co/mtAjxl8hLy
Cow spa video.Is that a roomba cleaning up hay?https://t.co/ECk60kP373
Mice in VR tho.https://t.co/2g3wG7sd7o
"should put a certain amount of doubt into the use of the mouse as a model organism to study things that affect serotonin signaling"https://t.co/CrazNyRxW4https://t.co/RgZKW6y8SA
We rethought serotonin signaling once. From "turning mice gay" to "this is just aggression & dominance behavior playing out". Just take it a step further."more mice will [be tortured] before scientists figure out exactly what role serotonin plays." https://t.co/fRh9F4Jq6t
Another paper on the weird ways that serotonin signaling occurs as a feedback loop between the gut and the brain within rodents. (h/t @Psychobiotic) "Host Microbiota Regulates Central Nervous System Serotonin Receptor 2C Editing in Rodents"https://t.co/GsSnsqMYwz
"This is perplexing, given the … clear evidence for harm associated with high red meat intake,"https://t.co/Asuz5kEptrWhat evidence? Are they talking about some shit surveys and an implication raised by TMAO that conflicts with research on fish consumption?
“harm the credibility of nutrition science and erode public trust in scientific research.”https://t.co/BnmTNrAEEgYou don't say.
“the hypothesis that TMAO is directly involved in development of atherosclerosis…seems like a paradox, as intake of seafood is generally accepted as cardioprotective.”https://t.co/zHSRmACt6q @DocCarnahan
@DocCarnahan And then... we get the really strange ideas.Like what if a parasite helps to regulate circulating cholesterol and modulates T cell associated immune processess; and all this fish is just a.... red herring?https://t.co/v0z4PRuHSOhttps://t.co/bGK8cTYSrG
@DocCarnahan What if effects of fish on Multiple Sclerosis is a statistical "Fluke"?"compliance of patients is predicted to be generally poor, and this is largely attributable to negative attitudes associated with the concept of being infected with live pathogens"https://t.co/3PhfQndZwr
"In populations endemically infected with helminths, Th1 and/or Th17 immune responses are compromised [...] A safer and more reliable alternative to live infection would be to identify the specific immune-modulatory molecules produced by helminth parasites."
I'm just so fucking salty I guess."Our results connect high salt intake to the gut–immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions."https://t.co/Vvk6Z8fZci
Immune cells fighting each other in a delicate regulatory balance. Tweaked by disease and diet? More likely thank you think.https://t.co/iPy869tazE
Warfare?https://t.co/evHyNd4KbT
What do you mean warfare?https://t.co/2FAA6qV1yx
@JimmyRis @InquilineKea @The_Lagrangian Inflammation -> white adipose recruiting -> supply of food."the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration."https://t.co/uEpudPgMFO
Salt intake can be bad in some circumstances."Ideally, dietary modification of salt intake, as well as eradication of H pylori infection, is a promising strategy for gastric cancer prevention throughout the world, especially in developing counties."https://t.co/ldCL9THj2O
Maybe there is something complex going on; some kind of complex regulatory system that tries to maintain homeostasis.https://t.co/dPI0RrT4ic
Shooting in the dark. Blind scientists guessing at risk profiles and shrugging.Take two and call me in the morning (Because I have no idea what these pills do)https://t.co/cErxiqlglE
"And in real life, my attending says “Huh, this looks vaguely autoimmune, let’s throw steroids at it.” And it always works." https://t.co/yKpEkuXad4 screaming.
We have no idea what we are doing to our bodies.https://t.co/LtOEOp5ecF
That scene from Idiocracy (movie that lampoons bureaucratic systems at all scales of society) where they're measuring gut microbiome, ear microbiome, and mouth microbiome. But they get it mixed up because it's become routine & no one seem to think anymore.https://t.co/sOa12Oa93V
Oh wait. That exists."H. pylori infection is one of the probable risk factors for CHD independent of history of DM, DLP, HTN, CRP status and IL-6 level." https://t.co/HcPDJG1B6n
and in a world where mouse models of disease are absolutely fucked... we have a result from 1999. We may need to rethink."Imunosuppression by a corticosteroid fails to exacerbate Helicobacter pylori infection in a mouse model of gastric colonization."https://t.co/xUzxyw4yHi
What if we're all wrong? Because we're blinded.Low status to be fat.https://t.co/8p4bFUMVSJ
"There is controversy regarding halitosis that may arise from the production of H2S by Helicobacter pylori, the pathogen responsible for gastritis"https://t.co/ilHEOVksOeFUCKhttps://t.co/jsuXcUhAm1
"If a causal link between Hp infection and MS is confirmed in the future, this may have a major impact on the pathophysiology and management of MS."https://t.co/dhU7XkfDiAOh shit. No. It can't be.
"Most infected individuals do not develop overt disease, leading to the hypothesis that some H. pylori strains are harmless or even beneficial[7]; however, the list of diseases potentially caused or worsened by H. pylori has been growing in recent years"https://t.co/dhU7XkfDiA
What if I just build my own asylum and call it a coffin and then hang out in there for like 6 months without eating?https://t.co/IQiYCH1qVv
This blog post nails exactly why I doubt GI readings as a standard metric."But fortunately for them, nutritionists don't let nonreproducible results stop them when those results seem to confirm a strongly held belief, no matter how unscientific." 🔥https://t.co/aloF1ToDxv
"Test three individuals and you will get three different values. The authors of the theory really stretch to explain why this happens, because nonreproducible results usually mean death for a scientific theory."Why gut+insulin studies like https://t.co/h5Mhw6OkJi are important!
"stress the animals and look at their behavior, [...] manipulate the animals' behavior with drugs and say, 'OK, these are going to be good anti-depressants.' But they are not treating depression; they are treating stress."https://t.co/g99m9FWGLEhttps://t.co/CRSKYi7MiK
So we isolate rodents — a poor surrogate for human serotonin, gut microbiota, brain structure, & microglia / immune system function — then test 'em by torturing & seeing how long they struggle.This is foundation of pharmaceutical science?Is that right? Am I missing something?
"When one moves to the human system, these linkages seem to break down rapidly. Translation between animal and human studies is complicated by the fact that animal models may not properly induce or recapitulate PD pathology."https://t.co/Rr5yOK9Khd
Science as bullshit?https://t.co/rnTXwCfG4EIf something is a popular headline, my instinct now-a-days is"I bet not"https://t.co/PpceFEGgzP
"I call; bullshit!"https://t.co/GzolSQwfHN
"TMAO = LMAO"https://t.co/cjrAFThg7K
Rats/Mice don't vomit.No vagus reflex?https://t.co/EFWYKoQSM7TRP Channels as mediator?https://t.co/x3MIrd2RS4TRPV1 doesn't work right?https://t.co/4eyCHC6uHTThey still get motion sickness (and respond via Pica behaviors)?https://t.co/LdlMLiBbKz
Scratching an itch.https://t.co/4s0zNx4KKz
"down the digestive tract where they are modified into immune-regulatory molecules by gut bacteria. The modified bile acids then activate two class of immune cells: regulatory T cells (Tregs) and effector helper T cells, specifically Th17" (in mice)https://t.co/0pIjO0GtQi
TH17 regulated via bile acid and gut microbes you say?https://t.co/IobEzdo8CJ
I think I figured out human hibernation, but I need to see if I can induce it in mice first (without torturing them).Let's just say: TH17 and impact on neuroinflammation and neurodegeneration at intersection of immune system & diet is very interesting.https://t.co/U3LiQZsmkr
"Bile acids promote lipid uptake and respond to food intake. Bears do not eat for up to 6 months during hibernation, which likely explains the reduced bile acid levels in the winter."https://t.co/FdRrUYBqZMhttps://t.co/nik0GQnaQC
"Blockade of the CB1 receptor in these mice results in decreased food intake, indicating that at least part of the anorexigenic effect of leptin is due to decreased [Endogenous cannabinoid signalling]."https://t.co/NXFaeip9ntThis Bears 🐻 repeatinghttps://t.co/DPvrIs5vhT
"However, understanding MS as metabolic rather than an autoimmune begins to bring the disease and its causes into focus."https://t.co/rKV0tLckzo"These studies reveal several metabolic checkpoints with specific regulation of TH17 cells"https://t.co/CaVY8KeKsC
"In conclusion, children with ASD exhibited a differential response to T cell stimulation with elevated IL-17 production compared to controls."https://t.co/LXtGZednxMhttps://t.co/LVyDF2LZKW
I fixed my autism symptoms by pretending I had metabolic issues associated with diabetes type II, of which gut microbiome was just one aspect. I suspect you can shortcut around the whole needing to eat poop for 3 months straight if you boostrap your metabolism via fast. But N=1.
IL-17 thohttps://t.co/0ZfXpIl5eHhttps://t.co/XXMWSwZWLHhttps://t.co/gvkz0JRshNhttps://t.co/2Eif6ogxTWAutism, caused by immune system dysfunction assoc w/ schizophrenia and multiple sclerosis ala whitematter degradation? Muh Corpus callosum hates me.https://t.co/ceOZkSIdCL
Do you know what happens in mammals who hibernate? Their immune system and metabolic system changes.These two systems are necessarily related.The question is: HOW?or maybe... WHEN?https://t.co/RQ3tFdXab2
Funny that the endocannabinoid system impacts metabolism and inflammation. It's almost like the two are necessarily related.https://t.co/sGLGtRegL1
"A new idea comes suddenly and in a rather intuitive way. That means it is not reached by conscious logical conclusions. But think it through afterwards you can always discover the reasons which have lead you unconsciously to your guess" https://t.co/i6mP9i9DQ1
"Taken together, we conclude that the neuroprotective action of endocannabinoids involve the endogenous biosynthesis of H2S via the cysteine aminotransferase dependent pathway in the bovine retina."https://t.co/h4juges2hJCOW EYES? Why were we looking at cow eyes?
WTF"to treat simple indigestion of dairy cattle. Transfaunation refers to transferring a broad spectrum of micro-organisms including bacteria, protozoa, fungi and archaea from the rumen of a healthy donor animal to the rumen of a sick recipient animal"https://t.co/2OPf87eoqd
"Around the mid-1900 s, scientists began to explore the benefits of rumen transfaunation and the associated microbial populations. Rumen transfaunation has been used clinically to treat indigestion and to enhance the return of normal rumen function"https://t.co/oTebgdJ3KC
Wait. That suggests that prior to transfaunation, there may have been other medical procedures and dietary aids that would have improved their rumen microbiota.I wonder if there are ancient texts on ruminant veterinary care that rival Avicenna's work in humans.
I love this caption."Mommy kisses (aka transfaunation)"https://t.co/KzHLk6yt6v https://t.co/W82qc9AXXA
I wonder if we take calves away from mothers so early (as part of the milk production process) that we end up not letting caves eat cowshit or get necessary colostrum for their rumen.I had never thought to dig into animal husbandry to mine for microbiota in medicinal history.
"(1.5kg) of fresh manure from a healthy and recently dewormed donor horse. We mix it with water and filter off the solid particulate material. [yields] "liquor." We then pump the fresh liquor through a stomach tube into the recipient horse's stomach."https://t.co/4cvHAzHdRU
"When compared to CD4+ T cells from non-drug-using controls, CD4+ T cells from cannabis users showed an approximately 50 percent decrease in proinflammatory IL-17"https://t.co/AYocVLO9zAhttps://t.co/mD1GMyQOjG
IL-17 thohttps://t.co/0ZfXpIl5eHhttps://t.co/XXMWSwZWLHhttps://t.co/gvkz0JRshNhttps://t.co/2Eif6ogxTWAutism, caused by immune system dysfunction assoc w/ schizophrenia and multiple sclerosis ala whitematter degradation? Muh Corpus callosum hates me.https://t.co/ceOZkSIdCL
"... close to the entirety of our current understanding of CB2 signaling and influence on the cytokine secretome has been obtained from models which exhibit considerable limitations in modelling normal human physiology" ¯\_(ツ)_/¯https://t.co/Nu8YDrdoZjhttps://t.co/Vc3rgY9Yqd https://t.co/WqjtwWT5TD
Doctors a thousand years ago knew about cannabis' anti-inflammatory properties. Meanwhile, the first endocannabinoid was discovered in 1992 (Anandamide)https://t.co/7e1maKQHrpTFW: I'm learning more about human biology from Muslim poets than I do modern science. 🤪
Something fishy?"The phenolic antioxidant resveratrol, often referred to as the anti-atherosclerosis principle in red wine, inhibits TMAO production by reduced TMA production after remodelling the gut microbiota"https://t.co/1AkU7GtJCe
I hear this https://t.co/53VaVRhxcv thing is pretty cool.https://t.co/YiKaJrADGG
What if it's not the cholesterol?https://t.co/R1gRY9MD9I
Did you know that eggs contain choline, and increase TMAO which has been linked to heart disease. Also fish has been linked to TMAO but they might reduce heart disease? What about grass fed eggs that aren't missing omega3s? Does it matter if your egg was raised next to cows? https://t.co/wU9H0YAFvr
"The researchers found that when ursolic acid was combined with either curcumin or resveratrol, the natural compounds prevented the uptake of glutamine by prostate cancer cells, which prevented tumor growth in the mice."https://t.co/ZeJJKt95P3
Weird, it's almost like foods that have chemicals known to re-engineer gut microbe populates have an impact on the process of prostate cancer growth. https://t.co/smAfum6Q1R
What is a heterocyclic amine, and why does it seem to disrupt gut microbes?https://t.co/FZTP4rOt8fXenobiotics, in my processed food? https://t.co/vim4SjdPkOMore likely than you'd think.
Apparently scientists have decided to harrass rats by their tails via vibrating them at varying frequency to show that they produce different levels of reactive oxygen species?https://t.co/wC8w6OfBFC
Suggests that the hand-vibration problem from video game controllers (and heavy machinery) may be partially driven by mitochondrial function.https://t.co/KFHMZIavoS
Rubbing a couple drops of THC tincture on an itchy spot (heat rash?) made it stop itching and the redness go away. https://t.co/llhhSRXNn3https://t.co/EHqsKDa6aX
"TRPV1 becomes rapidly desensitized upon activation, rendering the channel refractory to further stimulation."https://t.co/h779QWLU3e"[anandamide] is a [poor] TRPV1 agonist that behaves as a partial agonist in tissues with a low receptor reserve" https://t.co/HWzKdCGBP2
Note to self: that was an observation on a friend. I don't seem to get a lot of red when I itch. Might be due to mutations having to do with niacin flush / Mast cell responses to allergies.https://t.co/lVzJ8Mq5MN
"one type of bacteria associated with meat consumption can take the TMA, [...] and metabolize them without producing any TMAO. That means those bacteria are in effect severing a key link in the cardiovascular disease chain." https://t.co/cRfwZQhEluhttps://t.co/VlsCCy23yg
My goal in life is to troll you into making friends with the life-giving organ that lives in your rectum.https://t.co/ouxILdc9k5
I treat drugs as food, and food as drugs.Exploring how soups serve to extract terpenes from herbs that have psychobiotic properties, impacting the gut, and the brain.https://t.co/WJEQ7mljdV
A spoon full of beetroot helps the medicine be absorbed in the intestine.https://t.co/sGyp3bHexrIn the most delightful way.https://t.co/4sc9XJ1wf6
citation #118: "Prebiotic potential of pectins and pectic oligosaccharides derived from lemon peel wastes and sugar beet pulp: A comparative evaluation."https://t.co/uxjHkGqbedMary Poppins takes on her new staring roll as "The immortal yoga mom".https://t.co/yp9CJgFjfd
I'm going to wash my face with a natural source of sapponins, followed by dousing it with apple cider vinegar to target what I think is a chronic yeast infection causing beard dandruf, and then afterward coat it in ghee to reduce inflammation.I am turning into a yoga mom.
"To explain these disparate findings, other factors may be involved in the TMAO-health and disease story. In the video, I discuss the impact of kidney function on plasma levels of TMAO, disease and mortality risk." via @mike_lustgartenhttps://t.co/GkVBU8yVgw
Did you know that Uric Acid & Creatine concentrations (a common artifact of diabetes) contributes to TMAO production when under dialysis?https://t.co/t7rfNYSLZ7https://t.co/zypVMfYBX3
Hand drawn graph from a 1925 paper on purine levels in fasting and rates of uric acid expulsion. Wish my handwriting was this good.They found all sorts of weirdness in how kidneys concentrate uric acid during fasting states.https://t.co/tTp8YLVzIV https://t.co/zLAfkuNYjD
Diabetes is a risk factor for heart problems and also kidney problems.https://t.co/9eahmCVVfoThat's why I've been exploring it in bears as part of trying to figure out how to hibernate safely.https://t.co/HgaiZEkmWX
I don't think about it as risking my life, so much as de-risking it.Also, super useful if in testing hibernation "Unlike bears, once kidney damage occurs in humans, it is permanent with no options other than kidney transplants or long-term dialysis."https://t.co/0teVuUjXJF
As far as I can tell, Sumo Wrestlers have low rates of kidney problems despite their perceived size. Tho there are cases where a genetic fluke in uric acid production causes issues.https://t.co/rEex1eLCVwhttps://t.co/3RbLeQFMZ0
IIRC many problems we see in Diabetes is caused by uric acid crystals building up... Flushing it might help. But why is it there to begin with? Maybe celery is acting on gut microbes in similar way as why it makes nitrates for meat preservation? Hmmhttps://t.co/QoZOL5f1oB
FMO3 leads to obesity & TMAO"The TMAO-Producing Enzyme Flavin-ContainingMonooxygenase 3 Regulates Obesity and the Beigingof White Adipose Tissue" https://t.co/aOuaGxXGyS
FMO3 from a metabolic activation and impacts kindey issues."Metabolic Activation of Flavin Monooxygenase-mediated Trimethylamine-N-Oxide Formation in Experimental Kidney Disease"https://t.co/ngJg06ap3t
I'd bet money that Serotonin (and/or Andenylyl Cyclase) are one of the main factros driving kidney problems associated with diabetes and kidney failure seen in Scizophrenia. By way of smooth muscle problems in the Kidneys.https://t.co/F1E4yIhmXW
@vgr They tested against opossum kidney cells (a common set of cells for research at the time) and it seemed to shut off Adenylyl cyclase by how it acts on serotonin receptors. Finding suggest it's an agonist for that receptor (which I think is how it makes my nose run/produce mucus).
Serotonin associated medications are hugely problematic for kidney function."Experts aren't certain why SSRIs have the potential to put pounds on folks who take them, but there are some theories. "https://t.co/1eqYtWKypIhttps://t.co/oaFv709VJk
Did you know that people w/ kidney issues are harder to treat safely with SSRIs?Kidney problems w/ MDMA: https://t.co/X7VksKVWhh"Serotonin (5HT) has significant effects on renal metabolism and glomerular function and is a potent renal vasoconstrictor"https://t.co/1XJouWvtXe
Skin in the game.https://t.co/kiTZceIMRF
What if I told you that all of this research is promulgated on a hypothesis that I can cure my girlfriend's type 2 diabetes thru diet by using various terpenes to bias her microbiome... and all this about dicks is proxy research to hormone-microbe ties.https://t.co/zZ9obc2BGY
"Topical nasal decongestants such as Afrin (oxymetazoline), Neo-Synephrine (phenylephrine), Privine (naphazoline), and Vicks VapoRub Inhaler (l-desoxyephedrine/levmetamfetamine) can also cause an increase in blood pressure."https://t.co/fA49AYcjZp
TMAO might be good actually."Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function."https://t.co/pdG9GtO1nuhttps://t.co/e9mIoNMbjp
Would be funny if there are entire rodent labs who raise rats carefully because of cannibalism, but it turns out they just don't have the right microbes to eat carbs because they don't let them cycle feces like rats in the wild. https://t.co/eSGvIXNmYbhttps://t.co/i1AXYYKSJX
Don't look directly at the microbes, this stresses out the rat.https://t.co/uuink77eMH
I have strong feelings on those 1950s rat park experiments involving sugar on lab mice. There are some really fascinating changes to gut microbes that occur as a result of morphine, and stress. But lets just pretend these studies are gospel.https://t.co/Lostkxir8e
Rats will eat their own feces when under stress. So instead of taking the stress away, we just make their habitat prevent them from eating the feces and conclude it must be the stress that is making them sick.https://t.co/Dt4R9KvYkx
If a mouse was covering itself in shit, do you think we would try to stop that? What happens if we prevent self-medication by restricting behaviors meant to help augment metabolic-immune axis driven by TRP pathways from chemicals in an animal's gut?https://t.co/FB6IbCSelf