[HN Gopher] Nanoparticle-remodeled gut microbiota slows neurodeg...
       ___________________________________________________________________
        
       Nanoparticle-remodeled gut microbiota slows neurodegeneration via
       gut-brain axis
        
       Author : bookofjoe
       Score  : 102 points
       Date   : 2023-11-10 20:29 UTC (1 days ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | pfd1986 wrote:
       | In mice.
        
         | scns wrote:
         | Yes but we have to start somewhere.
        
         | stavros wrote:
         | Which is stronger evidence for humans than "in nowhere".
        
         | flappyeagle wrote:
         | This is the stupidest glib reply format on par with "citation
         | needed" and "tell me you're [thing] without telling me you're
         | [thing]"
         | 
         | Animal models are used in research. Is this news to you? Do you
         | think people don't know that?
        
           | calf wrote:
           | "In mice" is one of those shorthand sayings that
           | scientists/professors themselves coined, it's not as
           | dismissive as you're making it out.
           | 
           | In this context of social media it's very useful as a
           | reminder.
        
         | l8_to_catch_up wrote:
         | And not just any mice; specially bred mice.
         | 
         | So it's not even generalizable to all mice, much less humans.
         | 
         | More studies are needed.
        
         | andriesm wrote:
         | Ib my younger days I used to get all excitef about new
         | scientific breakthroughs. After decades I know better and apply
         | the heuristic of disregard whenever I come across the hidden
         | punch-line "In mice".
         | 
         | It really is a very good metric for preventing you to get
         | sucked into hype that will 99.99 percent of the time result in
         | exactly zero real world impact 10 years later.
        
       | pella wrote:
       | Another option for people is to have a fecal microbiota
       | transplant.
       | 
       | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019775/ Fecal
       | microbiota transplantation in Parkinson's disease--A randomized
       | repeat-dose, placebo-controlled clinical pilot study
       | 
       |  _" Conclusions: Subjects with Parkinson's disease tolerated
       | multi-dose-FMT, and experienced increased diversity of the
       | intestinal microbiome that was associated with reduction in
       | constipation and improved gut transit and intestinal motility.
       | Fecal microbiota transplantation administration improved
       | subjective motor and non-motor symptoms."_
        
         | bboygravity wrote:
         | The good ol shitswap.
        
           | account-5 wrote:
           | A good ol' turdtrade.
        
             | Etheryte wrote:
             | A poop-loop, if you will.
        
               | OscarTheGrinch wrote:
               | ))><((
        
               | falcor84 wrote:
               | Wait, what? As far as I understand, there's a donor and a
               | receiver - I don't see any reason for this to loop back.
        
               | dartos wrote:
               | Yet
        
         | LinuxBender wrote:
         | Maybe I'm too chicken to receive someone elses poo but I took
         | what I consider to be the more scientifically controlled middle
         | ground, mixing large amounts of probiotics with MCT oil and
         | using it rectally. 36 strains, about 2 trillion CFU. To my
         | surprise I have found several doctors that love this idea and
         | one that also does it. It's not as diverse and that is exactly
         | why I do it. I know what cultures I am getting and what
         | benefits each one has.
         | 
         | Or maybe I have discovered a fetish.
        
           | andai wrote:
           | Fascinating, hadn't heard of MCT nor rectal administration of
           | probiotics (save for FMT).
           | 
           | Do you get them in pills and then mix it with coconut oil or
           | what? (Or does it need to be pure MCT)
        
             | LinuxBender wrote:
             | I open the capsules and mix them. I've tried to get the
             | company to sell me a bag or can of the probiotics but they
             | won't do it. Not a big deal though, it doesn't take long to
             | open them. I just use the large containers of coconut MCT
             | oil. If there is something that would be better for the
             | bacteria and for the large intestine cells I would love to
             | know.
        
               | andai wrote:
               | Heh they're probably scared you'll start selling the ass
               | formula!
        
               | LinuxBender wrote:
               | Hurry up and trademark that.
        
           | yellow_lead wrote:
           | Whats your benefit from this? Do you credit it with any GI
           | improvements?
        
             | LinuxBender wrote:
             | Benefits:
             | 
             | - Bypass the stomach acid, preserving more bacteria
             | 
             | - Keep the bacteria out of the small intestine _mostly_ to
             | avoid SIBO and avoid having to chase the probiotics with
             | Betaine hcl, Ginger root, digestive enzymes, etc... to keep
             | the small intestine clear which can trigger inflammation.
             | Also not having to pre-coat the small intestine with
             | cranberry molecules to cover any section that is missing
             | the mucous layer.
             | 
             | - Feed the colon and large intestine cells MCT oil without
             | having to consume it.
             | 
             | - Anecdotally I feed better for several days after doing
             | this. I can do faster power-walks for longer. _I do not run
             | to protect my cartilage._
             | 
             | - The only GI improvement that I can _feel_ is the lack of
             | discomfort from taking large amounts of probiotics orally.
             | 
             | - Very large amounts taken orally can result in small
             | amounts making it past the intestine cell junctions and
             | triggering a small immune response which may have both
             | positive and negative ramifications but that's a much
             | bigger topic.
             | 
             | - Less likely to disturb the mucous layer.
             | 
             | Drawbacks:
             | 
             | - To be useful requires a large amount of bacteria and that
             | requires a large amount of MCT oil and getting into
             | positions to get it up into the large intestine. Well ...
             | it has to come out some time and being liquid one must stay
             | near the restroom. _There 's no holding it in._ Some kind
             | of paste injector tube would be better, probably something
             | similar in form factor and design as the vaginal yeast
             | infection treatments perhaps. If this were a product I
             | would buy it even though it would be harder to get it into
             | the large intestine.
             | 
             | - The first few hours after can feel _weird_ as the body
             | has to adjust.
        
               | rokkitmensch wrote:
               | Have you attempted to mechanically stopper yourself
               | during this process to increase the treatment duration?
        
               | LinuxBender wrote:
               | I have not. Just guessing but I think it might have to be
               | custom made or uncomfortably tight. Maybe others have
               | done this. The doctor I know that does this makes these
               | little frozen things in a custom freezer tray meant for
               | enemas.
        
               | rokkitmensch wrote:
               | Check Amazon, there are a zillion shapes and materials to
               | explore.
        
               | shepardrtc wrote:
               | Wouldn't the oil just lube it up so it would eventually
               | get shot out like a bottle rocket?
        
               | LinuxBender wrote:
               | Another challenge with this is that the formula I use has
               | prebiotics so it's just a matter of time before gas
               | builds up and things could get painful. I will likely
               | just stick with my method of staying near the restroom.
        
           | InSteady wrote:
           | Do you mind sharing how you decided which 36 strains to
           | include and what they are? Bonus points for links to studies
           | (or articles with good references).
           | 
           | :)
        
             | LinuxBender wrote:
             | I plan to add a health section to my awful blog. That is
             | where I would be linking to the list of cultures and links
             | to the benefits and risks for each one. If you want to read
             | up on which formula I am currently using ahead of time it
             | is here [1] and if you mouse over the images one of them
             | lists which strains they use. I alternate between them and
             | a couple of other blends. Most of the strains have some
             | studies on nih.gov which is best searched using google with
             | "site:nih.gov probiotic culture_name benefits"
             | 
             | [1] - https://www.amazon.com/NewRhythm-Probiotics-
             | Digestive-Prebio...
        
           | thenerdhead wrote:
           | Have you done actual GI / microbiome tests before and after
           | to see any cause/effect? Sounds a bit extreme when you could
           | just follow the 4 K's of Kefir, Kombucha, Kimchi, and Kraut
           | over a long period of time.
        
             | LinuxBender wrote:
             | _Have you done actual GI / microbiome tests_
             | 
             | I have not. I can not find any labs that I can trust and
             | that have not been hacked on a regular basis.
             | 
             |  _Sounds a bit extreme_
             | 
             | It may be. I reset my gut bacteria some years ago and use
             | this to improve the overall gut-scape. The 4 K's are great
             | but my personal preference is to use this method that if
             | for no other reason it is banned by WADA. If they consider
             | it cheating then I like it that much more.
        
               | thenerdhead wrote:
               | https://humanmicrobiome.info/testing/
        
         | Aurornis wrote:
         | There are online communities of people attempting FMT on
         | themselves. I remember seeing them even cite an online source
         | of FMT supplies from some sketchy company operating
         | internationally to avoid regulations. Others used very
         | understanding family members or friends as sources.
         | 
         | I haven't followed the topic for a long time, but I distinctly
         | remember how many people were disappointed with the results of
         | their self administered FMT. This is probably because they had
         | unreasonable expectations about their health conditions being
         | caused by the microbiome. The only real success stories were
         | from people who had C. Diff and treated it with a combination
         | of antibiotics and FMT.
         | 
         | However, there were a lot of negative stories. Some people had
         | major bowel problems for a while. One person even died, though
         | it was speculated that it was due to some of the microbiome
         | altering antibiotics he was experimenting with.
         | 
         | Interesting research topic, but please don't DIY it.
        
           | andai wrote:
           | The guy who died wasn't DIYing it.
           | 
           | > The first person known to die as a result of a fecal
           | transplant is a 73-year-old man who developed a fatal
           | infection with antibiotic-resistant bacteria that were in the
           | donor's stool sample.
           | 
           | > News of the man's death surfaced in June; he was one of two
           | patients in separate clinical trials who became ill after
           | receiving fecal transplants from the same donor
           | 
           | https://www.livescience.com/fecal-transplant-death.html
        
       | lambdaba wrote:
       | Using gold nanoparticles.
        
       | polskibus wrote:
       | What's chiral Au? Can we get it OTC?
        
         | gilleain wrote:
         | Interesting. So 'chiral' is another word for 'handedness' -
         | your hands are chiral, in that you can't rotate your left hand
         | in such a way that it looks like your right hand (yes I know
         | what the Greek word for 'hand' is).
         | 
         | So I assumed that these would be gold atoms with a chiral
         | molecule around them - the ligand, that is. However, from a
         | quick search it appears that there are these gold nanoparticles
         | that are chiral shapes. In other words, the structure of the
         | particle is chiral, not the molecule itself.
         | 
         | In any case, I doubt you can get them over the counter any time
         | soon, but who knows.
         | 
         | edit: Here is a nice looking review that is free to read :
         | https://www.nature.com/articles/s44222-022-00014-4
         | 
         | Seems like there are a variety of different techniques but
         | Figure 2d in that review shows an image referencing - 'Lee,
         | H.-E. et al. Amino-acid- and peptide-directed synthesis of
         | chiral plasmonic gold nanoparticles. Nature 556, 360-365
         | (2018)'
        
       | xchip wrote:
       | 'slows' is click-baity, we should mention the two numbers
       | (average and std)
        
       | xitrium wrote:
       | The last thing I read about the link between amyloid-b
       | accumulation and Alzheimer's was that the entire field was full
       | of fake data ( https://www.science.org/content/blog-post/faked-
       | beta-amyloid... ). In particular, even treatments that directly
       | reduce amyloid-b in the brain did not restore cognitive
       | abilities.
       | 
       | At least this paper tests both cognitive abilities as well as
       | "amyloid-b pathologies." I'm not at all an expert in this field
       | but gold nanoparticles sounds like something you'd see on a late
       | night infomercial, lol.
        
         | Etheryte wrote:
         | Don't worry, it's not just this field, roughly 70% of medical
         | studies are fake or severely flawed [0].
         | 
         | [0] https://news.ycombinator.com/item?id=37572394
        
           | mft_ wrote:
           | That may or may not be the case, but you're rather detracting
           | from the original comment, either deliberately or not.
           | 
           | The issue in the Alzheimer's world is the possibility that
           | _the very disease mechanism concept underlying the vast
           | majority of research and interventional trials into which
           | countless multiple billions have been poured, is incorrect_.
           | 
           | Within that space, this is orders of magnitude more
           | fundamental and serious than a flip aside that lots of trials
           | have problems, so who cares about another?
        
             | epistasis wrote:
             | > the very disease mechanism concept underlying the vast
             | majority of research and interventional trials into which
             | countless multiple billions have been poured, is incorrect.
             | 
             | Not "is incorrect," but _might be_ incorrect. And we almost
             | certainly won 't know it is correct until we actually have
             | a therapy.
             | 
             | Those pursuing cures could have waited until there was more
             | solid science, but they and their funders took on the risk,
             | knowing full well that the amyloid hypothesis is not
             | proven.
             | 
             | This is not some indictment of science, this is normal risk
             | taking for a problem that hugely affects society.
        
               | smolder wrote:
               | > Not "is incorrect," but might be incorrect.
               | 
               | That's why the part you quoted is preceded by "the
               | possibility that".
        
               | epistasis wrote:
               | But the entire framing of the comment is that the amyloid
               | hypothesis is taken as fact and not possibility, when in
               | fact _the core research question_ is whether it is true
               | or not.
               | 
               | It is the best possible explanation so far, but four
               | decades of research have not reached a definitive
               | conclusion.
               | 
               | An open problem is not a problem for science, that's the
               | fundamental focus of science. The problem is people
               | misrepresenting what science is and what it aims to do.
        
           | InSteady wrote:
           | Ah, the game of telephone.
           | 
           | >For more than 150 trials, Carlisle got access to anonymized
           | individual participant data (IPD). By studying the IPD
           | spreadsheets, he judged that 44% of these trials contained
           | _at least_ some flawed data: impossible statistics, incorrect
           | calculations or duplicated numbers or figures, for instance.
           | And in 26% of the papers had problems that were so widespread
           | that the trial was impossible to trust, he judged -- either
           | because the authors were incompetent, or because they had
           | faked the data.
           | 
           | Firstly, this is only from one journal, _Anesthesiology._
           | Second, the phrase  "at least" indicates that while 44% had
           | some amount of (presumably) flawed data, only 26% of the
           | studies were bad enough to be judged fake or severely flawed
           | by this one (admittedly esteemed) researcher in the field of
           | anesthesiology. It's important to be skeptical and do your
           | homework when you hear sweeping and/or shocking results. It's
           | also important to read carefully, especially with science
           | journalism because it is written for clicks and broad
           | audiences, not to reduce ambiguity and adhere to strict
           | standards of accuracy.
        
             | svnt wrote:
             | I didn't go look up the quote but based on your version
             | here it sounds like roughly half (44%) had some kind of
             | suboptimality, and of those roughly a quarter (26%) had
             | serious problems preventing them from being relied on.
             | 
             | That means 11% of the total papers should be discarded,
             | which means 89% of the papers can be used.
        
               | InSteady wrote:
               | As per usual, science reporting fails to use precise
               | language. It can be interpreted either way, although I
               | think your interpretation is the slightly larger leap
               | based on phrasing. In any case, it is far below the 70%
               | (and not directed broadly at all scientific research)
               | that GP states.
        
         | instagraham wrote:
         | It's hard to discern discourse in a field one is unfamiliar in,
         | I'd tried with the Alzheimer's fiasco. Here's my tuppence:
         | 
         | The plaques are known to be linked to Alzheimer's, the
         | debunking of one paper that messed with its figures does not
         | detract from the whole body of research. The inefficacy of
         | plaque-targeting treatments may not be proof that the plaques
         | are not causal in nature, only that their damage is not
         | reversible/fully understood.
        
         | epistasis wrote:
         | In a massive field, one researcher does not constitute "full of
         | faked data," despite how concerning it is.
         | 
         | The problem is viewing individual papers as the unit of truth
         | in science. The "self-correcting" nature of science will
         | actually reject entire papers, and entire directions of
         | inquiry. Including, maybe, a casual relationship between beta
         | amyloid and AD, but maybe not.
         | 
         | The other key part of science is holding everything in a state
         | of uncertainty. There's some "facts" but mostly just hints and
         | clues. And with Alzheimer's disease in particular we are trying
         | to make progress with completely inadequate vision; we really
         | can't even measure so much of what we want to measure. Feynman
         | said it back in the 1960s, too, physicists have failed to
         | deliver the tools to biologists to really measure what needs to
         | be measured. There have been advancements, and DNA sequencing
         | technology in the past decade has been turned into the most
         | clever sorts of information theoretic microscopy by combining
         | DNA sequences with many other biochemical processes. But we as
         | a species still can not measure a lot of the things we'd like
         | to measure.
        
           | SubiculumCode wrote:
           | A most eloquent response that needed to be said.
        
           | brnaftr361 wrote:
           | But he's correct, amyloid plaque theory was founded on bad
           | data. Amyloid plaques as causal agents is unclear, but it was
           | made to appear clear by poisoned data, and many studies
           | conducted afterwards, in good faith, assumed that the
           | information and conclusions were sound. However it doesn't
           | appear to be the case, and instead something along the
           | amyloid beta pathway is more likely to be the true causal
           | factor, and plaques an association. It has spawned something
           | of a wild goose chase in Alzheimer's research and treatment.
        
             | epistasis wrote:
             | The faked data is not foundational to the field, if we are
             | to believe the article linked from that comment.
             | 
             | > But my impression is that a lot of labs that were
             | interested in the general idea of beta-amyloid oligomers
             | just took the earlier papers as validation for that
             | interest, and kept on doing their own research into the
             | area without really jumping directly onto the _56 story
             | itself. The bewildering nature of the amyloid-oligomer
             | situation in live cells has given everyone plenty of
             | opportunities for that! The expressions in the literature
             | about the failure to find_ 56 (as in the Selkoe lab's
             | papers) did not de-validate the general idea for anyone -
             | indeed, Selkoe's lab has been working on amyloid oligomers
             | the whole time and continues to do so. Just not Lesne's
             | oligomer.
             | 
             | And
             | 
             | > Did the _56 Work Lead to Clinical Trials? That's a
             | question that many have been asking since this scandal
             | broke a few days ago. And the answer is that no, I have
             | been unable to find a clinical trial that specifically
             | targeted the AB_ 56 oligomer itself (I'll be glad to be
             | corrected on this point, though).
        
           | xitrium wrote:
           | I appreciate your commitment to modernist capital-S Science
           | here :) I'm familiar with how the field ought to work but
           | after working in Andrew Gelman's lab for some years, also
           | with how it can fail us. Here I think the researcher in
           | question has had a much larger impact than you are allowing
           | for. Here's a choice quote:
           | 
           | > Every single disease-modifying trial of Alzheimer's has
           | failed.
           | 
           | > The huge majority of those have addressed the amyloid
           | hypothesis, of course, from all sorts of angles. Even the
           | truest believers are starting to wonder. Dennis Selkoe's
           | entire career has been devoted to the subject, and he's
           | quoted in the Science article as saying that if the trials
           | that are already in progress also fail, then "the A-beta
           | hypothesis is very much under duress". Yep.
           | 
           | And the original expose is quite interesting if you haven't
           | read it yet
           | https://www.science.org/content/article/potential-
           | fabricatio...
        
             | epistasis wrote:
             | The hypothesis was under great duress even in 2004, when I
             | took a protein structure course that spent a lot of time on
             | prions and the beta amyloid. Many people have devoted their
             | careers to chasing this down, only one as far as we know
             | published impactful fake data.
             | 
             | However, the particular faked data, despite lots of
             | citations, has apparently not lead to any clinical trials:
             | 
             | > Did the AB*56 Work Lead to Clinical Trials? That's a
             | question that many have been asking since this scandal
             | broke a few days ago. And the answer is that no, I have
             | been unable to find a clinical trial that specifically
             | targeted the AB*56 oligomer itself (I'll be glad to be
             | corrected on this point, though).
        
         | Aurornis wrote:
         | > In particular, even treatments that directly reduce amyloid-b
         | in the brain did not restore cognitive abilities.
         | 
         | Correct, but this doesn't constitute "fake data". It could be
         | that amyloid-b is a marker rather than a causative factor. Or
         | it could be that amyloid-b related damage is downstream, and
         | remove amyloid-b after the damage has been done won't remove
         | the other damage.
         | 
         | It's too quick to wave away an entire field because a single
         | theory didn't pan out. Most medical research proceeds with a
         | lot of dead ends before it is figured out.
        
           | xitrium wrote:
           | Very true, but it seems like you may not have seen the expose
           | on this field in Science
           | https://www.science.org/content/article/potential-
           | fabricatio...
        
       | fer wrote:
       | Medicine isn't my field, but I wonder why the chirality, why
       | gold, why microbiota as target, why those particular diseases?
       | 
       | As in, I might be searching wrong, but I can't find previous
       | research that would hint in this particular direction, and I
       | think it's reasonable to be skeptical about any "random button
       | pushing"-looking research showing positive results.
        
         | epistasis wrote:
         | Sometimes the only difference between random button pushing and
         | science is if you write it down.
         | 
         | Faff around and find out is the essence of the scientific
         | method.
         | 
         | That said, I never trust a paper that gets posted directly to
         | HN much. But then, single papers are never to be trusted!
        
         | InSteady wrote:
         | I can't speak to chiral gold, but as for exploring the
         | connection between microbiota and neurodegenerative diseases,
         | this is a hot area of study. Take a sentence from the abstract:
         | 
         | >The gut-brain axis has emerged as a therapeutic target in
         | neurodegenerative diseases by modulating metabolic activity,
         | neuroimmune functions and sensory neuronal signaling.
         | 
         | You can pretty much formulate a few dozen google searches from
         | various keywords in that sentence + "microbiome," "microbiota,"
         | and/or "GI immune signaling," etc and come up with hundreds of
         | papers. The GI tract is host to the majority of our immune
         | system. Many of the molecules used for signaling (and all kinds
         | of other tasks) come directly from the bacteria there, or else
         | are dependent on bacterial metabolites as inputs.
         | 
         | On a related note, I expect we will hear more about the
         | metabolome in health and medicine research. As microbiome is
         | the set of all microbes in the body, metabolome is the set of
         | all metabolites (bacterial and endogenous) in the body. In this
         | study, serum levels of an indole were found to be altered in
         | Alzheimer's patients:
         | 
         | >indole-3-acetic acid, which was lower in serum and
         | cerebrospinal fluid of patients with AD compared with age-
         | matched controls.
         | 
         | In another study of MS patients, two other indoles, as well as
         | butyrate, were found to be lower in serum concentration
         | compared to healthy controls [1]:
         | 
         | >Highlights - Gut microbiota and metabolites profiles of
         | individuals with MS differ from healthy controls. Individuals
         | with MS have reduced serum levels of indolepropionate.
         | Individuals with MS have reduced serum levels of indolelactate
         | and its producing bacteria. Individuals with MS have lower
         | levels of species and genes involved in butyrate production.
         | 
         | Indoles in particular may be an interesting avenue of research
         | [2]:
         | 
         | >What is the function of the indole in bacteria? Indole has
         | recently been implicated as an important small molecule signal
         | utilized by many bacteria to coordinate various forms of
         | behavior. Indole plays a role in numerous bacterial processes,
         | including: biofilm formation and maintenance, virulence factor
         | production, antibiotic resistance and persister cell formation.
         | 
         | [1] - https://www.cell.com/cell-reports-
         | medicine/pdf/S2666-3791(21...
         | 
         | [2] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175420/
        
         | arrosenberg wrote:
         | Something of an educated guess, but microbiota because there
         | are current hypotheses that rely on the gut-brain interaction,
         | gold probably because its inert, and chirality is most likely
         | because their target requires specific kinetics.
        
         | crdrost wrote:
         | Alzheimer's is the most common form of dementia, affecting tens
         | of millions of mostly elderly people, characterized by the
         | brain getting "gummed up" by various mechanisms like reduced
         | interconnectivity of your neurons, the formation of these
         | plaques of a protein called amyloid beta on the brain tissue,
         | tangles of a different protein called tau, and little "pearls"
         | of a sort called vacuoles wrapping not sand grains but little
         | lumps of hardened proteins. So there's a theme of proteins
         | being where they're not supposed to be and misfolding and so
         | on.
         | 
         | There are several partial causes of these protein problems,
         | including genetic factors, chronic high blood pressure, smoking
         | history, depression history. One can alternatively characterize
         | this as a sort of inflammatory response, which puts it in a
         | bucket with Parkinson's and ALS and other things tied to
         | oxidative stresses and long-term inflammation.
         | 
         | I am not a physician but was trained as a physicist, part of
         | where I know about this stuff comes from trying to research a
         | speculative YouTube video that I never got around to making
         | called "the biophysics of weight loss" where I would tell
         | people that from a physics perspective, the scale in your
         | bathroom lies, calories are necessary but not sufficient to
         | understand the problem, feedback networks are complicated, and
         | just in general tried to educate the public about basic physics
         | from a direction that is not Newtonian mechanics. (So if you
         | want to start with energy, what is the most frequent
         | interaction with measured amounts of energy everyone has? It's
         | either diet or the wattage ratings on electric bulbs, diet
         | seemed more fun.)
         | 
         | So where this gets interesting for me is, in trying to talk
         | about the complex feedback loops and signaling and satiety
         | around diet, diet and lifestyle factors do seem to affect these
         | chronic levels of inflammation. Just a simple example, your
         | blood has to maintain a strong homeostasis with respect to how
         | much sugar is in there, too little and your cells don't have
         | what they need, too much and bacteria could thrive inside of
         | you. One mechanism the body uses is, if we detected the blood
         | as too sugary, we dump this signaling molecule called insulin
         | in there too. Muscle tissue will take up blood sugar without
         | insulin, but fat cells need the insulin as a "key" to open a
         | lock that lets sugar in for long-term storage as fat. But the
         | fat cells have what we in computing would call backpressure--
         | they don't just respond directly to insulin, they calibrate
         | their response to what they can handle. If too much sugar is
         | coming in and I can't store it, I reduce my sensitivity to the
         | insulin, so that I take in less sugar for a given amount. If
         | this happens chronically enough, you get a general insulin
         | resistance, and that leads to high blood sugar, type-2
         | diabetes.
         | 
         | Well, elevated blood sugar does something else that is linked
         | to Alzheimer's: the Maillard reaction. This is the crusty
         | delicious browning that happens when we sear a steak, or bake
         | bread. The natural sugars in the muscle and natural proteins in
         | the flour are enough in either case, the formula is sugar plus
         | protein plus heat equals denatured brown crusty proteins. You
         | are warm enough on the inside that this does "sous vide" your
         | proteins very slowly, it is part of aging. So if your blood
         | sugar is high, you age faster. The term in the literature is
         | "advanced glycation" if you want to read more about this.
         | 
         | I don't have diet recommendations, I am just interested because
         | I can ask prospective students "if we turned you into a hot
         | dog, how far would it stretch" and other silly things like
         | that. I will say, keto was originally invented to help with
         | epileptics, and it does that by moving the brain off of sugars
         | and to a fuel that the brain "prefers" (in the sense of having
         | fewer barriers to letting it in) called ketone bodies.
         | Intermittent fasting also does this on shorter timescales.
         | 
         | Anyway, the story about the gut microbiome maybe playing into
         | this is even more complicated, some people talk about "leaky
         | gut," others say that that is crackpot, but the basic gist is
         | that there is a theory that if you do not eat enough soluble
         | and insoluble fiber, your gut microbiome (which needs to eat
         | both to survive) essentially maybe eats you a little bit
         | instead as it starves. And this causes you to be at war with
         | your gut microbiome, and it means that the good bacteria that
         | are not eating you are less able to crowd out the bad ones that
         | want to eat you... And the claim is that this creates a
         | constant chronic low-level inflammation, so there's that
         | oxidative stress and early aging problem again, and so forth. I
         | don't know that I believe this? But it does have me staying
         | away from fruit juices, which are like fruit but you removed
         | both the soluble and insoluble fiber.
        
         | thenerdhead wrote:
         | Read Ed Yong's book "I Contain Multitudes". This area has been
         | more/less blocked for many decades and with recent innovations
         | and pipelines we may be able to start finding causal patterns.
        
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