r/science • u/mvea Professor | Medicine • May 27 '19
Medicine The gut’s immune system functions differently in distinct parts of the intestine, with less aggressive defenses in the first segments where nutrients are absorbed, and more forceful responses at the end, where pathogens are eliminated. This new finding may improve drug design and oral vaccines.
https://www.rockefeller.edu/news/25935-new-study-reveals-gut-segments-organized-function-opportunities-better-drug-design/444
u/SirKnightofDerp May 28 '19
Why would the gut wait until the end to rid food of pathogens? Right as it is about to exit our body anyways?
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May 28 '19
Response to pathogens earlier in the gut could cause problems with absorbing nutritional content in those parts of the digestive tract/cause inflammation or other issues as a RESULT to immune system response to those pathogens. This is my speculation though.
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u/Dontbelievemefolks May 28 '19
So would people with auto immune /digestive and food allergies also have issues with nutrient absorption? Could a food allergy also manifest as a nutritional deficiency?
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u/stvbles May 28 '19
I'm sure a Wheat/Gluten allergy does inhibit your absorption of specific things. Iron is definitely one of them which is hard enough to get in anyway if you're having issues.
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u/solosolosolosolosolo May 28 '19
The gut contains small needles called "villi" attached to the wall, which contain good blood flow and are responsible for transferring nutrients into the bloodflow. As I understand it, when a person with celiac disease for example has gluten, their villi shrivel up and curl in, causing them to become malnourished even if they are eating. (all could be wrong)
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u/EmilyU1F984 May 28 '19
The vili get complety obliterated if someone suffering from celiacs disease continues eating gluten. The immune response will eventually destroy them completely .
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u/GETitOFFmeNOW May 28 '19
B12 deficiency and resulting nerve damage affects half of patients diagnosed with celiac disease. This study shows that 41% had B12 serum less than 220 pg/mL, but fully half with numbers below 500 also are deficient.
American physicians may note that in Japan, B12 supplementation is implemented at 500 pg m/L.
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May 29 '19
I had low B12 levels and a folate deficiency caused by an different immune condition. The deficiencies were not caught early and biopsies later confirmed small fiber sensory neuropathy and other neurological issues. I'm doing much better with supplementation but it's been a drag.
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May 29 '19
I am currently diagnosed with a mast cell disorder, which means part of my immune system is misbehaving, and it also causes major GI issues and I also have nutrient absorption issues. Both of the deficiencies are related and as I understand it both are absorbed near similar areas of GI tract, so it may explain it.
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May 28 '19
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u/Tauber10 May 28 '19
Celiac disease as well. You basically starve because you can't absorb nutrients properly.
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u/umopapsidn May 28 '19
Much higher rates of diarrhea from things we now shrug off seems like an evolutionary disadvantage.
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u/Targetshopper4000 May 28 '19
I have colitis and this is true. Inflammation can hamper absorption of nutrients. Luckily , I guess, my inflammation is right at the end.
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u/P-Schwayne May 28 '19
The segmentation is within the small intestine, so immune activity ramps up right before it enters the colon not right before it exits the body. This is important because the colon is a controlled “infected” space with bacteria that help to break down food.
If the distal small bowel didn’t have heightened immune capabilities, you would have retrograde overgrowth of bacteria (this can happen- it’s called SIBO).
Anatomists have known for a long time that the small bowel has increased lymphatic tissue (Peyers patches) for detecting germs at the terminal end. I think this study more or less just shows that this specialization also occurs on the molecular level?
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u/shastaxc May 28 '19
I have had SIBO (that went untreated for 5 years). It's very painful.
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u/Spitinthacoola May 28 '19
How have you been treating it? Know someone who deals with this. Also, do you know which form you have?
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u/MaximilianKohler May 28 '19 edited May 28 '19
Do a search for an article titled
SIBO — valid term or misnomer based on incorrect understanding of the gut microbiome?
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u/shastaxc May 28 '19
While some of the other causes of those symptoms are valid concerns, I was also tested for all of them. I had 2 colonoscopies/endoscopies with biopsies, an ultrasound, and MRI, tests of pancreatic enzyme deficiency, and intestinal parasites, Crohn's, celiac, allergies, and more. The SIBO test was the only one with positive results, the only effective treatment, and re-testing 6 months later showed negative result of recurrence.
So at least in my anecdotal experience, I cannot agree with that article.
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u/hypnos_surf May 28 '19
"Having immune responses separated by location likely increases the chance that the immune system reacts appropriately to what’s passing through, Mucida says. Once most nutrients have been absorbed, the system can focus more aggressively on eliminating pathogens without interfering with food uptake."
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u/Ceryn May 28 '19
Probably in the selective choice between a bit of diarrhea and starving to death. Diarrhea won.
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May 28 '19
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u/stvbles May 28 '19
On the other end of that I've only had the cleanest solid ones for months now after some stomach issues. It's a weird but satisfying feeling.
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u/Birdbraned May 28 '19
have you looked into the availability /cost of doing fecal transplants? I was reading a few years ago that that helped a good proportion of people in a pilot study, there's probably more information about that now?
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u/GETitOFFmeNOW May 28 '19
My uncle claims he cured the C. Dif. he obtained at the V.A. Hospital with weed brownies and CBD oil.
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u/MoneyTreeFiddy May 28 '19
It was a bug fix tacked on at the end of development, and wasn't in the original plans.
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u/complacentguy May 28 '19
the colon will strip any moisture from the fecal mater as it passes thru. If the small intestine didn't kill the pathogens before they entered the colon then it would be easier for them to enter the blood stream and effect the host.
I think. :D
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u/greyjackal May 28 '19
the colon will strip any moisture from the fecal mater as it passes thru.
I wish...
(long history of diarrhoea that's somewhat related to diet but nothing that we can pin down. And by "long", I mean 10 years.)
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u/Birdbraned May 28 '19
pathogen =anything not allowed in the body.
Food allergies are what you get when that section of the gut immune reaction is over active.
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u/noiamholmstar May 28 '19 edited May 28 '19
There's less need to fight pathogens in the early part of the gut because they haven't had a lot of time to grow yet. Everything we eat has some level of bacterial contamination, though generally it's pretty low. Anything that can survive the acidic environment of the stomach is going to start reproducing. By the time it reaches your latter portion of your intestine there is a lot more bacteria in it than there was as it was leaving your stomach. It makes sense that there is much more immune activity in the latter portion of the intestine as well. There's a lot more to fight back.
People look at dogs and the fact that they can eat things that would make humans sick, but dogs also have a much shorter digestive tract, and it only takes about 12 hours for food to pass though their system compared to about 24 hours for humans. A species of bacteria might double in population say, every 20 minutes or so. So a human that eats something questionable has a lot more "doubling"s to deal with than a dog and therefor a much higher bacterial load.
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u/anna1138 May 28 '19
Would this be different for people with ulcerative colitis and crohns?
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u/godminnette2 May 28 '19
I have ulcerative colitis. It resides in my colon and the end of my large intestine, so this seems to track with my experience.
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u/fokjoudoos May 28 '19
The colon is your large intestine. Did you mean "my colon 'at' the end of my large intestine"?
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u/dpark95 May 28 '19 edited May 28 '19
He mightve just meant the rectum when he said end of his large intestine, since that is essentially what the rectum is
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u/gotsanity May 28 '19
As someone with Crohn's I would say that it makes sense to me. My condition presents primarily in the ilieum and continues through a section of large bowel. My gastro doc always described Crohn's as an overactive immune system response that thinks our own body is a foreign invader and decides to go nuclear. Crohn's is literally your bowels on hard mode.
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u/ZenZenoah May 28 '19 edited May 28 '19
My question as well. Jpouch for 7 years.
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May 28 '19
My daughter is is scheduled for her final jpouch surgery next month! Closing everything up and done with it!
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u/Amlethus May 28 '19
There are also potential implications for our understanding of Celiac Disease, and for many food intolerances in general.
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u/m-a-k-o May 27 '19
Doesn’t this kind of make sense? I know diseases like ulcerative colitis start at the lower part of the rectum and travel up from there as the disease gets more severe
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u/sewankambo May 27 '19
Yep. And the more we study the gut the more we realize how integral it is to everything going on in our bodies.
I have UC and treating the gut / bacteria / microbiome has done more for me than meds.
There was another post earlier today on Reddit that linked gut health with mental health as well. We need to study the gut more.
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u/bakinbacon May 28 '19
Hey, I was recently diagnosed with Crohn's and was wondering what kind of things you've done to treat your gut. I've been stuck on mesalamine for a year now and right now I'm curious to see how others are dealing with their UC/Crohn's since these meds are starting to not work as well as they were before.
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u/so-vain May 28 '19
Read the longevity paradox and/or the plant paradox. I have severe crohns and those books are changing my life.
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u/zirooo May 28 '19
Next step is chemical immunomodulators like Azathioprine 6mp, or biological anti TNF drugs like Remicade, Humira, Simponi...etc
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u/Javaman420 May 28 '19
Hi there, I hope you don't mind me asking but I was wondering if you could tell me more about what it can feel like to have UC and what you've done to treat it?
I've had a pain that comes and goes on my left side for about 6 months now. At it's worst it can feel like the bowl is inflamed and gives pain in the lower back. But normally just a sharp stab from time to time. My doctor is very slow to act and had me drinking psyllium husk for a long time. I think I messed up my gut bacteria when I did keto for a year. I've had various problems throughout my body since then.
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u/terriblebugger May 28 '19
I found out I had it due to mucus-like and eventually blood-tinted stuff when I went to the toilet, which I had to increasingly often. Faecal calprotectin are easy stool sample tests to measure inflammation if you’re worried.
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u/ihaveasandwitch May 28 '19
Hi can I get the same pm as the other guy regarding treating gut issues? I had gut issues that I have treated, but I'm always concerned they might come back as they have for me in the past.
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u/TheBirminghamBear May 28 '19 edited May 28 '19
Pretty clear to see how evolution cultivate this development. Individuals with a much stronger immune reaction in the first part of the gut would increasingly see immune reactions to food, resulting in inflammation, malabsorption, and decreased fitness.
So selection would sort out individuals with mutations for asymmetrical distribution of the immune system across the gut.
The whole "paleo" diet has gotten a deserved degree of scrutiny for the whole "eat like we evolved to" not having strong clinical evidence to support it, but I think it's very important to separate out the notion of eating specifically the types of foods we evolved to eat with a more general analysis of how things like orally ingested medicines, artificial foodstuffs like manufactured compounds and other things not likely to exist in nature may be affecting the gut and, by extension, the entire body.
In general, I see a sort of tradeoff here. On the one hand, we've fortified our diets and made food far more accessible than it ever has in the past, and I believe evidence bears out a positive increase in overall fitness and things like strength and height from the past few thousand years.
However, I think there's been a hidden cost, specifically in mental development. The more this gut/brain axis comes in to focus, the more I think it's clear that specific foods and compounds, especially pesticides, are having a net negative effect on the gut microbiome, which in turn is having chronic negative affects on mental development and mental health.
The positive benefits have masked the negative benefits, but they've likely existed independently from one another.
A population has better and more ready access to adequate calories, macro and micronutrients, so people live longer, have increased health and fitness, etc.
But, to control that food supply, they need to add additives, flavoring to make it more palatable, and use damaging and dangerous pesticides to keep pests away from the crops.
These additives are not enough to decrease the overall increase in fitness conferred by the better diets, but I believe they are having an impact on mental health, which is the most intricate and complex of human developmental activities.
While things like vaccines are being attacked by the ignorant as causing autism and other conditions, I believe that there very well may be a rise in learning, behavioral and other spectrum disorders, but I think the more we study these, the more we'll find that things microbiome sensitivity to pesticides or other antimicrobial agents are a big factor.
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May 28 '19
I want to add a slightly different perspective to this: I was taught that from an anthropology perspective, the transition of early human populations from nomadic hunter-gatherers to sendentary agriculturalists had a net negative effect — one that we’ve only begun to negate in the last ~200 years thanks to a considerable number of medical advancements. For example, when ancient human remains are discovered, you can identify them as being part of an agricultural community by: short height, evidence of stress in the bones, abscesses in the jaw, compacted teeth/unruptured wisdom teeth in adults, and another bone-wasteing disease that I can’t remember the name of, but it’s due to poor nutritional value. To begin with, farmers didn’t live longer than hunter gatherers.
The crops we grow today, while more fortified, are an incredibly selective group of foods compared to the number of plants/animals available to eat. The crops we grow also have a lot of sugars in them (i.e. carbohydrates — although we stick cane sugar in a lot of processed foods too), and overall still aren’t as varied as hunter-gatherers. Hunter-gatherers were quite healthy, and didn’t face as many diseases as we do today (no close living quarters with pests and waste because they are always on the move). We now live longer than they did, but we still have problems with teeth and “modern” diseases.
All that being said, the correlation between mental development and digestive issues is fairly well known. (On a mobile, but you can find many papers studying the correlation between Autism and GI issues in particular, like this one https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981895/)
(I’m definitely not qualified enough to have a valid say in all this — it’s just a subject I have an interest in!)
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u/--Sigma-- May 28 '19
While mostly anecdotal, there seems to be a lot of people who benefit from a low-to-zero carb diet. I wonder if these effects are related to your theory.
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u/TheBirminghamBear May 28 '19
If I recall, some science on diets like the Keto diet postulated that a lot of the mental benefits from these low carb diets are in the release of orexin, which regulates wakefulness and is also linked to narcolepsy. When taking in a lot of carbohydrates, some individuals have orexin cycles negatively impacted, which then leads to decreases in satisfaction and arousal, which creates a sort of malaise, inattentiveness and brain fog that is alleviated entirely on low carb diets.
But I believe there are strong genetic components to this. It seems pretty binary; people either get high off keto diets or have no reaction.
Whether the gut/brain axis is involved in that cycle as well as others I don't know, but I'd say more probably, sustained damage to the gut flora allows antagonistic flora to thrive, which creates an immune response in the gut in the form of inflammation, which is sent along the gut brain axis to the brain, where it's interpreted as a form of pain or distress that is interpreted as existential feelings of apathy and anxiety by the cortex, which is great at picking up negative signals but very lousy about sourcing them to their origin.
In other words, at least in my theory, distress in the gut is like a loud warning signal in the consciouss mind, but you have no idea where it's coming from and so just assume it's due to the pointlessness and hopelessness of life, rather than an imbalance in the species of bacteria in your colon.
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u/basasvejas May 28 '19
Maybe a dumb question, but still would love to hear an answer. What happens to the gut flora when we take antibiotics? They die, i assume. But how do they exit the gut. How does the gut recover? Is it likely that taking antibiotics also affect brain? How do we recover the healthy flora after the course of antibio?..
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u/TheBirminghamBear May 28 '19 edited May 28 '19
But how do they exit the gut.
Through exactly the way you might think they do. Out the poop chute. Fun fact: about 30% of the total mass of stool is just dead bacteria.
How does the gut recover?
If there are enough of the bacteria still surviving, they will multiply over weeks or months until the colony reaches the stable equilibrium it exited in before.
However, if there are not enough of the bacteria, or if other, more harmful bacteria now kill off or prevent the helpful gut flora from thriving, then the population will never recover.
This is part of the theory behind fecal transplantation. Once thought an absurd concept, the practice of taking fecal matter from a healthy individual with a thriving gut flora population and transplanting it into someone with a deficiency is actually gaining a lot of traction as a solution for many intestinal maladies.
Is it likely that taking antibiotics also affect brain?
Likely? It's hard to say. Once upon a time, it would have been a resounding "no", but now, that's unclear. Antibiotics and destructive therapies like chemo therapy are almost certainly doing damage to gut flora, which in turn is almost certainly harming or causing adverse effects in an individual. In most cases, this is probably an acceptable trade-off; dealing with stomach issues is better than dying from cancer, after all.
But the aforementioned fecal transplantation and other treatments may gain more ground as measures to help a patient fully recover if a therapy has irreversibly killed off their gut flora.
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u/GETitOFFmeNOW May 28 '19
There's certainly something that is interfacing between us and our world that's causing an objective rise in autoimmune disease. MS is 250% more common, celiac disease is 450% more common than it was in the fifties (found by comparing blood draws from the 50s). One would be foolish not to examine the effect of the thousands of unregulated chemicals that we dump into our own habitat.
When I am good, I eat paleo and need to get back into it fully. I try to eat as varied a diet as possible, with lots of different veggies daily to give my microbiota some support.
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u/Nerd-Herd May 28 '19
I thought they already knew this and that's why some pharmaceuticals are designed to be absorbed in the first section of the intestine
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u/teamonmybackdoh May 28 '19
As far as I know that has to do more with what is absorber where, vs what portion of the intestine fights what. What irks me about this article though is the claim that this is some entirely new thing. It even states that the intestine appears to be uniform throughout...this is just nowhere near true. Every physiology text details dramatic variation in both the immune functions as well as the absorptive functions of different parts of the gut. This research is still significant, but the article is ever so slightly sensationalized
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May 28 '19
This is understood by anyone who has had food poisoning. If after vomiting you have the shits your in it for the long haul.
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u/Kamizar May 28 '19
Honestly, this just sounds like oral medicine is for general things like "cold" or "flu," and then we should take suppositories for everything else.
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May 28 '19
Does the location of colon cancer correlate with the weaker/stronger defense responses within the colon?
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u/WobblyBobbleNoggin May 28 '19
That's fantastic to hear that this could help improve oral vaccines! The impact of that would be huge for everyone, not just in comfort but in lives saved due to accessibility! I imagine it's easier to send pills through the developing world than ampules.
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u/Liljagare May 28 '19
Which is why in a fistula operation they can cleave your butthole pretty much, and it doesn't get infected, even though you probarly poop once a day!
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u/YourMindShifts May 28 '19 edited May 28 '19
I wonder how this affects people who have parts of their GI tract removed. Do they experience more infections correlating to surgery in the farther intestinal areas?
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u/NEXT_VICTIM May 28 '19
More aggressive immune response leads to more pathogens being killed off. Whoda thunkit?
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May 28 '19
FYI Your whole immune system consists of roughly 2 kg bacteria located in your stomach and intestines. My mind was blown away at the pure weight of it.
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u/chocobeatz May 28 '19
Before I clicked on the thread, I thought to myself "An exciting gut paper! I wonder if H.C. or D.M. are involved?" Then I saw D.M!
I spoke with D.M.'s mentor H.C. before and would love to meet D.M. himself. Excuse me for my scientist fanboyism!
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u/mvea May 27 '19
The title of the post is a copy and paste from the photo caption and first two paragraphs of the linked academic press release here:
Journal Reference:
Compartmentalized gut lymph node drainage dictates adaptive immune responses
Daria Esterházy, Maria C. C. Canesso, […]Daniel Mucida
Nature, volume 569, pages126–130 (2019)
Link: https://www.nature.com/articles/s41586-019-1125-3
DOI: https://doi.org/10.1038/s41586-019-1125-3
Abstract
The intestinal immune system has the challenging task of tolerating foreign nutrients and the commensal microbiome, while excluding or eliminating ingested pathogens. Failure of this balance leads to conditions such as inflammatory bowel diseases, food allergies and invasive gastrointestinal infections1. Multiple immune mechanisms are therefore in place to maintain tissue integrity, including balanced generation of effector T (TH) cells and FOXP3+ regulatory T (pTreg) cells, which mediate resistance to pathogens and regulate excessive immune activation, respectively1,2,3,4. The gut-draining lymph nodes (gLNs) are key sites for orchestrating adaptive immunity to luminal perturbations5,6,7. However, it is unclear how they simultaneously support tolerogenic and inflammatory reactions. Here we show that gLNs are immunologically specific to the functional gut segment that they drain. Stromal and dendritic cell gene signatures and polarization of T cells against the same luminal antigen differ between gLNs, with the proximal small intestine-draining gLNs preferentially giving rise to tolerogenic responses and the distal gLNs to pro-inflammatory T cell responses. This segregation permitted the targeting of distal gLNs for vaccination and the maintenance of duodenal pTreg cell induction during colonic infection. Conversely, the compartmentalized dichotomy was perturbed by surgical removal of select distal gLNs and duodenal infection, with effects on both lymphoid organ and tissue immune responses. Our findings reveal that the conflict between tolerogenic and inflammatory intestinal responses is in part resolved by discrete gLN drainage, and encourage antigen targeting to specific gut segments for therapeutic immune modulation.