[HN Gopher] The gut metabolite indole-3 propionate promotes nerv...
       ___________________________________________________________________
        
       The gut metabolite indole-3 propionate promotes nerve regeneration
       and repair
        
       Author : bookofjoe
       Score  : 203 points
       Date   : 2022-06-29 13:33 UTC (9 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | bookofjoe wrote:
       | "Here we show that IF [intermittent fasting] promotes axonal
       | regeneration after sciatic nerve crush in mice through an
       | unexpected mechanism that relies on the gram-positive gut
       | microbiome and an increase in the gut bacteria-derived metabolite
       | indole-3-propionic acid (IPA) in the serum."
        
         | voisin wrote:
         | I don't have a subscription, but I'd be interested to know how
         | long the IF protocol was (both duration of fasting and number
         | of weeks of IF) and what the human equivalent is. I understand
         | that there are reasons why a short IF regimen in mice equates
         | to a very long IF regimen in humans.
        
           | jbkkd wrote:
           | The pre peer-reviewed version is available here:
           | 
           | https://www.researchgate.net/publication/347663867_The_inter.
           | ..
           | 
           | > The IF group did not have access to food (fasting) during
           | the first 24 h and then every second day after that (e.g.
           | fasting during 0-24 h, 48-72 h, 96-120 h) with ad libitum
           | access to food on the alternating days (24-48 h, 72-96 h,
           | 120-144 h). Pre-weighed food was provided in the food hopper
           | of their home cage at 9:30 am (unless a fasting day for the
           | IF groups), and leftover food was weighed 24 h later.
        
       | seabriez wrote:
       | Why do I need nerve regeneration and repair? I get it if someone
       | is sick or whatever but healthy people probably shouldn't get
       | caught up in these snake oil treatments that they never needed in
       | the first place. It's great to raise awareness but unnecessary
       | for majority of healthy people.
        
         | NonNefarious wrote:
         | Who said you do? A lot of people have nerve damage from injury
         | or surgery.
         | 
         | I don't see where anyone promoted this as a normal regimen for
         | the general public.
        
         | whoomp12342 wrote:
         | depends on how you define healthy. for instance, someone might
         | have minor nerve damage from a severe injury but can otherwise
         | function like normal for the rest of their life.
         | 
         | do they NEED nerve regeneration? no. would it improve their
         | quality of life? yes.
        
       | diydsp wrote:
       | I searched for some foods to increase Indole-3 Proprionate and
       | this page is pretty good. [1] It tells what to eat (fermented
       | foods, fiber, sprouted seeds) and what to avoid (sugar, simple
       | starches, omega-6-heavy oils). It also introduced me to fermented
       | bean curd. Can't want to try it.
       | 
       | [1] https://go.ixcela.com/metabolite-library/ipa
        
         | srcreigh wrote:
         | If anyone goes through the citations here to find the
         | explanation of how refined carbs (fruit, white rice/flour) and
         | omega-6 oils detriment IPA production, would love to read about
         | it.
        
           | tpm wrote:
           | They displace food containing more fiber and by doing that
           | change gut flora to that which does not produce IPA.
        
           | Heston wrote:
           | Fruit is not a refined carb...
        
             | srcreigh wrote:
             | I assumed that simple sugars count as "refined carbs" and
             | simple sugars are found in lots of stuff including fruits.
             | Btw, my hope is that this very restrictive diet actually
             | isn't necessary for this metabolite.
        
               | Heston wrote:
               | By definition they aren't refined. You would have to
               | remove the fiber to make those sugars refined as a first
               | step. Fruit isn't pure simple sugars and it certainly
               | doesn't act that way in the gut when buffered with fiber.
        
           | icegreentea2 wrote:
           | I think it's coming from this source
           | (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872783/) which
           | more or less just generally claims that "Western Diets" are
           | disruptive to gut microbomes.
           | 
           | Annoyingly, it doesn't really pin down what exactly it
           | characterizes as "the western diet". It does include
           | extracted oils and refined simple sugars (glucose and
           | friends). But where exactly stuff like pasta/rice/flour sit
           | is less clear in their description.
        
             | Maxion wrote:
             | You can look up SAD, the standard American diet for a
             | reference.
        
         | jerrysievert wrote:
         | prepare for a whole new world. I started with a red fermented
         | bean curd that had so many flavors that I stood dumbfounded
         | while my brain tried to sort it all out.
        
         | 2OEH8eoCRo0 wrote:
         | Thanks for this. It's interesting how many of these studies
         | reaffirm what we already knew. Eat yogurt, fruits, vegetables,
         | nuts, etc. Avoid sugar. We might not have known why these were
         | good for us but I've been seeing these "guidelines" for about
         | 30 years now.
        
         | Melatonic wrote:
         | Natto is amazing for SCFA (not specifically propionate though -
         | more Glutamate)
         | 
         | I believe traditional salami also has a little propionate
        
           | pstuart wrote:
           | Natto is also a great source of vitamin K2 (and I think the
           | only vegan one).
        
             | Melatonic wrote:
             | By far the highest source of K2 out of EVERYTHING (like
             | nothing else even comes close). Its truely great stuff for
             | your stomach
        
           | xtracto wrote:
           | I tried Natto and really really wanted to get to eat it every
           | day. However, one portion gave me huge long lasting
           | headaches. The flavour was good, and I am used to eat
           | ferments (I make my own vegan yoghurt). I was really sad
           | because Natto is supposed to have so many great properties.
        
             | Melatonic wrote:
             | Weird. Maybe try another brand? Some of them have weird
             | sauces included too you can skip
        
         | delibes wrote:
         | I didn't know about most of these fermented soy products -
         | https://en.wikipedia.org/wiki/List_of_fermented_soy_products
         | 
         | But Tempeh is a pretty common one for vegans. I've used it in
         | curries and stir fries.
        
           | blacksmith_tb wrote:
           | I think the problem is that Tempeh is always cooked, so I
           | would expect any critters in there to be dead (not that they
           | haven't done good work making it more digestible).
        
         | eigenrick wrote:
         | My Indonesian friend introduced me to tempeh, which has to be
         | one of the most versatile (and healthy) foods. You can toast it
         | for a quick snack, but it disappears into nearly every type of
         | sweet or savory dish, or it can be the main attraction. I've
         | put it into a meat red-sauce for added texture and protein. +1
         | would eat again.
        
           | azinman2 wrote:
           | Tempeh in Indonesia is great; it takes nothing like the
           | tempeh I've had in the states. Admittedly I stopped trying
           | over a decade ago because the disparity was so great. Can you
           | finally get good tempeh in the US?
        
             | dqv wrote:
             | Was it LightLife tempeh? That's the kind I get. I've never
             | had anything else, so I don't have anything better to ruin
             | it for me.
        
             | michael1999 wrote:
             | Anything I buy packaged is sad compared to fresh, home-made
             | tempeh. I'd start looking at "alternative" grocers that
             | also have fresh seitan.
        
               | SapporoChris wrote:
               | seven different types, twelve methods of cooking...
               | 
               | https://en.wikipedia.org/wiki/Tempeh
               | 
               | I've never had Tempeh, but I love tofu, edamame, natto
               | and other soy products. This is definitely on my list to
               | try and explore the many varieties.
        
         | calebm wrote:
         | The "omega-6-heavy oils" makes me think of the work of Dr.
         | Nemechek
         | (https://www.nemechekconsultativemedicine.com/nemechek-
         | protoc...), who works primarily with Autism. He found that a
         | variety of brain injuries that of various types (including
         | things like concussion), which historically have resolved
         | themselves, have, in recent years, stopped healing. So a
         | concussion that would have naturally healed a few decades ago,
         | keeps giving the patient problems. One of his primary
         | recommendations is to decrease the "omega-6 to omega-3" oils,
         | because it seemed that omega-6 cause brain injuries not to
         | heal. And it's worth noting that almost all vegetable oils
         | (canola, soybean, etc), which are in almost all "processed
         | foods" are high in omega-6.
         | 
         | This indole-3 link could be the reason why omega-6 oils are so
         | bad.
         | 
         | TL;DR: Don't eat processed vegetable oils (other than coconut
         | and olive oil).
        
           | janekm wrote:
           | Just be aware that that's a whole lot of conjecture with
           | little solid evidence behind it. Saying "these brain injuries
           | historically resolved but don't any more" sounds much more
           | like a change in diagnostics to me.
           | 
           | The evidence against seed oils / processed vegetable oils is
           | not very compelling yet (here's a pretty balanced summary:
           | https://www.healthline.com/nutrition/are-vegetable-and-
           | seed-... )
        
           | cung wrote:
           | Am I misunderstanding your comment? Olive oil and coconut oil
           | have terrible omega-6/omega-3 ratio, where as canola is
           | pretty good.
           | 
           | https://www.cancerschmancer.org/articles/healthiest-
           | cooking-...
        
         | redblacktree wrote:
         | Genuine question that's likely to sound flippant: Does beer
         | count as a "fermented food" in this context? What about wine?
        
           | mega_dingus wrote:
           | I don't know the pedantic answer to "is that fermented food"
           | 
           | However, alcohol is quite an irritant and (along with
           | caffeine) is the first thing a doc will tell you to cut out
           | if you have intestinal problems
           | 
           | Speaking (only) from personal experience, it can be such an
           | irritant that it more than outweigs the benefits of other
           | probiotics and "good foods" -- even in small amounts (e.g. 1
           | drink)
        
         | scythe wrote:
         | The recommendations on that page don't make much sense? The
         | foods recommended are not major dietary sources of tryptophan
         | (cf. [1]) and while a variety of fermented foods are mentioned,
         | I am not aware of the use of the crucial bacterium _Clostridium
         | sporogenes_ in any deliberate fermentative cultures, such as
         | are used for yogurt or kombucha, which rather contain [ _checks
         | fridge_ ] _Lactobacillus_ , _Bifidis_ , and _Streptococcus_
         | species. But _Clostridia_ are typically found in the gut of
         | breast-fed newborns within a week of birth [2], suggesting they
         | don 't need much help.
         | 
         | I will also note that there _has_ been some work done on the
         | incorporation of _Clostridium sporogenes_ into probiotics, but
         | it doesn 't come from kefir or miso, and... well... _just read
         | it!_ [3]
         | 
         | 1: https://en.wikipedia.org/wiki/Tryptophan#Dietary_sources
         | 
         | 2:
         | https://jasbsci.biomedcentral.com/articles/10.1186/s40104-01...
         | 
         | 3: https://scholarworks.calstate.edu/downloads/x920g252b
        
         | Rastonbury wrote:
         | The study is behind paywall, does it say to eat it? The
         | abstract just says delivery of Indole-3
        
         | Melatonic wrote:
         | The really interesting thing about fermented foods is that
         | EVERY single culture (often completely independent of each
         | other) developed their own unique ferments. Many were also
         | shared but have varietal differences. There are TONS most
         | people have never heard about. It is really sad that with the
         | advent of refridgeration we lost so many in common culture
         | (many or most are still niche). And I am not saying fridges are
         | inherently bad - we just should have also PRESERVED (get it?
         | BADOOSH) these practices
        
         | eurasiantiger wrote:
         | Indoles in general are common gut metabolites and an indole
         | proprionate sounds like a further metabolic product.
         | 
         | This leads me to believe that trying to increase
         | indole-3-proprionate specifically may be a fruitless journey
         | (pun not intended), and one would be better off by optimizing
         | for a hospitable environment for beneficial microbes in
         | general, for example by cutting out carbs but increasing intake
         | of flavonoids.
        
           | feet wrote:
           | I suspect you may be right. Many supplements that have been
           | tried just get broken down in digestion and don't actually
           | increase target levels in the target tissues, rather we need
           | to find ways of increasing the intake of precursor or
           | figuring out which microbiota are involved in the metabolism
           | and giving them a helping hand or just adding them altogether
        
           | fredophile wrote:
           | I don't have a citation handy but I know eating fermented
           | foods and increased fiber have both been linked to increased
           | gut bacteria diversity. Thus seems in line with what the GP
           | poster found for practical advice.
        
             | Melatonic wrote:
             | Its all about PREbiotics which are the food source for
             | probiotics or your gut bacteria. Which encompasses some
             | fiber and also sort of is its own thing. Long chain inulin
             | and resistant starch are both some good ones
        
       | bananapear wrote:
       | _Indole occurs naturally in human feces and has an intense fecal
       | odor. At very low concentrations, however, it has a flowery
       | smell, and is a constituent of many perfumes._
       | 
       | https://en.wikipedia.org/wiki/Indole
        
         | eurasiantiger wrote:
         | It is a semiochemical for many flowering plants.
        
         | jcims wrote:
         | Lilies always seem like they are on the precipice of smelling
         | like death. I wonder if it's the same thing.
        
           | ASalazarMX wrote:
           | Now I have the urge to find lilies and thoroughly confirm
           | this.
        
             | jcims wrote:
             | To me it's sweet from a distance and gets almost chemical
             | smelling when you get close. When you really get up in
             | there it feels like there's about to be a phase change in
             | the smell to something very unpleasant.
        
         | gpcr1949 wrote:
         | Interesting, however the indole ring is very common in
         | biomolecules, and is also present in tryptophan, serotonin,
         | melatonin and others. Most of these will not have fecal odors,
         | I3PA probably won't either. For another stinky indole
         | derivative, check out 3-methylindole.
        
         | badkungfu wrote:
         | Sounds like ambergris.
        
           | narag wrote:
           | Ambergris synthesis uses two opposite substances: ambroxide
           | and ambrinol. The former is clean, fresh. The later, similar
           | to indole, smells pretty awful in isolation, but gives depth
           | to the composition when both are mixed.
           | 
           | Indole is the characteristic smell of withered flowers.
        
         | [deleted]
        
         | briankelly wrote:
         | _I know you 'd like to think your shit don't stank, but
         | 
         | Lean a little bit closer, see
         | 
         | Roses really smell like poo-poo-ooh
         | 
         | Yeah, roses really smell like poo-poo-ooh_
        
         | mschuster91 wrote:
         | A derivate of that family is Skatole [1], with its name
         | appropriate to the fact that 1 gram can stink out a whole
         | factory hall (at 0.001446 mg/m3 stink tolerance [2], 1 gram
         | stinks up to 714.000 m3 of volume).
         | 
         | Fascinatingly, the same is valid here as for indole: at
         | extremely low doses the stuff can end up being used in perfume
         | [3].
         | 
         | [1] https://en.wikipedia.org/wiki/Skatole
         | 
         | [2]
         | http://web.archive.org/web/20170507164421/https://www.bmlfuw...
         | 
         | [3] https://www.parfumo.de/Duftnote/Skatol
        
         | imwillofficial wrote:
         | "Geez Honey, your perfume smells like shit"
         | 
         | "No, really, that's a compliment"
        
       | 0des wrote:
       | It also propagates roots in plants in the form of indole-3
       | butyric acid
        
         | gpcr1949 wrote:
         | That's a substance distinct from indole-3-propionic acid, so it
         | is not a form of indole-3-propionic acid.
        
       | zackmorris wrote:
       | I don't know much about this, but I've noticed an increase in
       | interest around adaptogens like ashwagandha, reishi, cordyceps,
       | and lion's mane:
       | 
       | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/
       | 
       | Going by my intuition, I suspect that the anti-microbial
       | properties of roots and fungi affect which gut bacteria are
       | active. Since bacteria can make anything, it seems plausible that
       | certain diets support healing and even some degree of
       | regeneration.
        
       | persedes wrote:
       | Having worked on microbiome / metabolome interactions I've seen
       | indole-3 propionate pop up for different phenotypes /
       | pathologies. Wondering if that was actually the correct
       | metabolite or just something related.
        
       | TylerE wrote:
       | ... in mice.
        
         | ASalazarMX wrote:
         | Hard to find human volunteers for sciatic nerve crushing.
        
       | mrwnmonm wrote:
       | I have zero knowledge on biology and medicine, could someone
       | explain this to humble people like me?
        
         | xtracto wrote:
         | This... someone should make an ELI5. It is always useful for
         | people like us :)
        
       | pid-1 wrote:
       | It seems gut microbes are in full rage lately.
        
         | majkinetor wrote:
         | It seems like we fucked up with antibiotics a lot...
        
         | zucked wrote:
         | Like the inner workings of the brain, the way the microbiome of
         | our body impacts our life is poorly understood. There will
         | definitely be a lot of FUD that will come from this, but the
         | TLDR for many of these studies seems to be: eat better quality
         | foodstuffs and you'll be better off.
        
       | fumeux_fume wrote:
       | This is certainly interesting, but without a wider understanding
       | of how the whole body works, it's not particularly useful on its
       | own.
        
       | upupandup wrote:
       | TLDR on increase i-3p:
       | 
       | - eat fermented food with non processed carbs (ex. rice & kimchi)
       | 
       | - practice intermittent fasting
       | 
       | Both of which I am doing and I can attest to the increased
       | productivity, mental acuity. In fact when I was eating well by
       | Western standards, I didn't quite feel like this, probably
       | because it takes forever to digest stuff like steak, fries etc.
        
       ___________________________________________________________________
       (page generated 2022-06-29 23:01 UTC)