16 ms·

Crohn’s Disease: Is the Cold Chain Hypothesis Still Hot?

276 points by fnord77 5y ago

Havoc 5y ago
Surely that correlates with a bunch of other stuff though like advent of processed food?
bserge 5y ago
Correlation between better living standards/food quality/medicine and people living with diseases that used to be fatal.
ineedasername 5y ago
It seems like a lot of this is equally explainable as better diagnosis, meaning CD could have been around at similar rates much longer but medical science just didn't diagnose it as such or at the same rates. It's a question you always have to ask when you see an increase in, well, most things: Is it an actual increase, or are we just better at noticing it now?
- abhisuri97 5y ago
  Surprised this isn't higher up. Crohn's was formally named/created as its own clinical entity in 1932 and the paper shows one of its graphs (Fig 1) starting in the 1940s. I doubt 8 years was enough for awareness to get out to the entire physician community about the existence of the disease and there were probably a lot of misdiagnosed cases in its early days (since crohn's has a clinically diverse presentation).
- commentsgaloer2 5y ago
  Anecdote of course, but my personal case may support this claim. My grandfather died when he was 34 (1960's) from an intestinal ulcer. Not diagnosed with anything. Born in south America but from Jewish immigrants (relevant as I've been told Crohn's is more prevalent among Jewish people) I was diagnosed with Crohn's when I turned 31, after having a colonoscopy because of severe diarrhea. Humira's been working so far, I've been on it for 2 years after other meds didn't do the trick. Edit: just in case it wasn't clear: I also had a pretty big intestinal ulcer. But getting diagnosed helped it not get worse, and after going on humira, it eventually got better
moralestapia 5y ago
Before some "wise guy" comes to parrot about how "correlation does not imply causation" [1], please, take some time to read the article as it has some valuable information. [1]: We've all heard that already, it doesn't impress anyone anymore.
- deleted 5y ago
  [deleted]
- uniqueuid 5y ago
  And it's not even in the article title. In fact, the text says " Figure 1A compares the annual incidence of the disease and the household equipment rate in several countries. There is a temporal correlation between these variables." A temporal correlation is something entirely different to a cross-sectional correlation (arrow of time etc.)
  - DantesKite 5y ago
    I tried researching what a temporal correlation is. Do you have short explanation for it?
    - uniqueuid 5y ago
      Temporal correlations are a family of things, since there are many degrees of freedom to choose what to compare with what. A very simple test is the "Granger Causality", which tests whether one timeline significantly predicts another one. You can formulate more complex models such as time series a predicting b with a certain lag. Ultimately, the idea is most often to remove unrelated factors (such as control variables, seasonality, self-influence i.e. autoregression) and then measure how well one series at t(0) predicts another one at t(1), while optionally doing some sort of hyperparameter optimization for the lag (i.e. determine which lag works best).
      - DantesKite 5y ago
        Thank you. Much appreciated.
teeray 5y ago
I wonder if anyone has tried a treatment with a non-refrigerated diet EDIT: I read some more and found “Nutritional treatment of CD was first proposed by Voitk in 1973. The treatment consists of administering a specific liquid formula…” It doesn’t say if that formula is refrigerated or not. My assumption is that it isn’t because it’s cited here, but that is an assumption.
- uniqueuid 5y ago
  Right, this is what the authors demand: "as no single experiment can definitively confirm the theory, we must continue to test it with additional works. Among them [and even if insufficient to definitively validate the hypothesis], a randomised clinical trial comparing patients with low versus high exposure to Yersinia would be an important step."
- teruakohatu 5y ago
  Essentially they found that tube fed diets do help, and they are effectively refrigeration free. > "Furthermore, no specific foodstuff has been incriminated in CD, and combining enteral nutrition with a highly controlled oral diet was recently shown to be effective" ... "It should be noted, however, that enteral nutrition effectively excludes refrigerated foods." They go on to say that enteral nutrition differ from regular diets so that the mechanism that make them work may not to the fact that they are unrefrigerated. A refrigeration free diet would not be impossible today, but hard. Given he prevalence of this bacteria today, non-electric cold stores would probably also need to be removed from the supply chain, making even a pre-industrial Western diet problematic. A sufficiently cooked vegan diet, minus everything that causes problems with people that suffer from Crohn's Disease, maybe would work? Ideally with vegetables that have not been refrigerated. Winter would be pretty bleak.
  - rini17 5y ago
    Pre-industrial western diet cold stored food was either salted (meat), fermented (cabbage, cheese) or alive (fruit, root vegetables, potatoes)...so, it's possible there was completely different microbiology than in modern processed food.
tomrod 5y ago
This is a bad title. Other trends since 1910 (the last 110 years) - Electromagnetic wave use increase via radio, television, cell and internet, and microwaves - Maximum altitude humans have reached - Number of bodies on Everest - Increase in pounds of enriched uranium and available thorium - Increase in the number of people who have read work by Ursula K. Le Guin and Isaac Asimov None of these have causal implications. But the article does connect a qualitative theory and show correlation -- suggesting the hypothesis could be a thread to chase down. This is the key thesis: > According to the cold chain hypothesis, the development of industrial and domestic refrigeration has led to frequent exposure of human populations to bacteria capable of growing in the cold. These bacteria, at low levels of exposure, particularly those of the genus Yersinia, are believed to be capable of inducing exacerbated inflammation of the intestine in genetically predisposed subjects. EDIT: Title: Crohn’s Disease: Is the Cold Chain Hypothesis Still Hot? Abstract: > Crohn’s disease [CD] is an inflammatory bowel disease of unknown aetiology. During recent decades, significant technological advances led to development of -omic datasets allowing a detailed description of the disease. Unfortunately these have not, to date, resolved the question of the aetiology of CD. Thus, it may be necessary to [re]consider hypothesis-driven approaches to resolve the aetiology of CD. According to the cold chain hypothesis, the development of industrial and domestic refrigeration has led to frequent exposure of human populations to bacteria capable of growing in the cold. These bacteria, at low levels of exposure, particularly those of the genus Yersinia, are believed to be capable of inducing exacerbated inflammation of the intestine in genetically predisposed subjects. We discuss the consistency of this working hypothesis in light of recent data from epidemiological, clinical, pathological, microbiological, and molecular studies.
- deleted 5y ago
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- jessriedel 5y ago
  Your first point is misaimed. They don't just note the historical worldwide rise in refrigeration goes along side a worldwide rise in Chrohn's. They compare the timing for Chrohn's and refrigeration for different demographic groups in different countries and even, if I am reading this correctly, at the level of individuals. The other things you list will not vary in the same way at that level of detail, although one must of course be wary of multiple hypothesis testing, forking paths, etc.
DantesKite 5y ago
It wouldn't surprise me if refrigeration contributes to the development of Crohn's disease. The causes can be multi-variate and anecdotally, from my own research, microbes (yeast, bacteria, fungi) all seem to play a key role. Anything that disturbs the balance in pathogenic ways can lead to dysfunction, especially antibiotics, but also a lack of plant cell walls in our diets. Everybody is slightly different, not just genetically, but in terms of the diversity of bacteria. There have been a few people who have managed to put Crohn's disease into remissions with raw kefir produced at home (the ones at store are not comparable) as well as with Visbiome, a probiotic produced in the lab with many studies behind it. And I've also heard the carnivore diet for short durations may help. There doesn't seem to be a consistent way to treat Crohn's disease and obviously, medicine to control flares is a must if the situation demands it. It does seem like a great many gut and autoimmune issues are somehow related to the diversity of microbes though and I look forward to more clinical research like this. We need all the help we can get.
- bladegash 5y ago
  Likewise on the welcoming of any bit of research! I ended up in the hospital about a year ago and found out it was the result of Crohn’s (34 years old). Another hospitalization, countless diet attempts, medications, and biologics, finally found something that worked, other than prednisone. If there is one thing I realized, it is that the effectiveness of treatments really is dependent on each individual’s biology. Possible foods that trigger me were completely fine for others I had spoken with, and vice versa. It’s encouraging to see as much research as there is and makes me hopeful not just for myself, but for others with the same condition (many who have it far worse than me).
  - jcrben 5y ago
    I got Crohn's about the same age (34). A couple years later at 36 I'm now on better health than I've ever been. I responded well to a biologic (vedolizumab aka Entyvio). But I also did exclusive enteral nutrition for months concurrently to help push me the edge. These days I eat a lot of sweet potatoes and chicken, with relatively little processed food. I also feel like theracurmin helps me https://pubmed.ncbi.nlm.nih.gov/32412598/ https://pubmed.ncbi.nlm.nih.gov/32412598/
emmelaich 5y ago
Good paper. If true I wonder how it could be combatted effectively. It's hard to do without refrigeration. Perhaps its related mainly to fast food, where the consistent refrigeration is less sure. CD has also been associated with Mycobacterium paratuberculosis, because that is implicated in the similar Jahne's disease in cattle and sheep: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894645/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894645/ Lastly, I also wonder if refrigeration has a role to play in Multiple Sclerosis. It also has strong relations with modern lifestyle and latitude (temperature). The suspect virus in the MS case seems to be https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus aka mononucleosis / glandular fever.
- laurent92 5y ago
  > It's hard to do without refrigeration. We’ve changed our diet since refrigeration is available. That’s an argument of vegetarians: Since we want meat, we need a refrigerator, which in turn makes us eat a lot of processed food. Frozen food, yoghurts, milk-based products, all of those are heavily processed, we try to “fill in the rest of the fridge”. My vegetarian friends reversed it: Eat veggies and fruits in quantity, grains, nuts, beans, bread, spices, oils… I’m a meat eater but I’m just passing the word: It is possible to live without refrigeration without compromising food, except meat.
  - cerved 5y ago
    I don't know, refrigeration seems pretty useful
  - Spivak 5y ago
    Every vegetarian but not vegan I know, including myself, eats dairy like crazy so I cant really say I experience this sentiment. Also fruits and veggies are basically the definition of food that needs refrigeration or “processing” for preservation. Strawberries that aren’t specifically bread to be hearty can spoil in less than a day. Prior to refrigeration we leaned on (and probably still do if you have a garden) canning, drying, pickling, fermenting — I mean making garlic confit was originally a way to preserve garlic. And you can preserve meat fine without refrigerators, that’s why we started salting, smoking and curing meat. The thing you compromise without a refrigerator is the ability to have truly fresh fruits, veggies, and meat for longer than the natural spoiling time.
lifeisstillgood 5y ago
There are a surprisingly large number of changes since ~1900 that have had big environmental effects on "modern life" that we are barely getting to grips with - this cold chain one is new to me but it fits in with electric lighting, urban noise and air pollution and even mass literacy etc as massive changes we can barely get to grips with I am deffo not arguing for some return to some paeleo, noble savage ideal. But our poor bodies evolved for something very different to eating burgers on a plane under flourescent lighting whilst reading text on a screen. Whatever we build as societies in the next 100'years, we should build at human scale.
- number6 5y ago
  Our bodys evolved to survive under harsh conditions until our offsprings are old enough to carry on (30 - 40 years) everything on top is bonus. Evolution and Biology have no agency. There is no moral, no right kind of living. If you procreate you fulfilled your biological "destiny". You can do that under eating a burger on a plane while reading on a screen. Evolution doesn't mind. Our bodys don't mind. Warrenty runs out in your thirties. Good thing we have brains that allow us to prolong our life's and increase our well-being.
  - deleted 5y ago
    [deleted]
  - rp1 5y ago
    I don’t think the GP was arguing that “evolution cares”. Rather, I think they were saying that we evolved as part of a system that moved at a certain speed. Changes to that system were reflected as part of the evolutionary feedback mechanism. Now, however, we’re changing the system so fast, evolution has no hope of keeping up.
  - enchiridion 5y ago
    Our brains were evolved.
  - ricardobeat 5y ago
    Well, clearly something goes wrong as children also get these debilitating diseases.
clouddrover 5y ago
This research group is developing a therapeutic Crohn's vaccine: https://crohnsmapvaccine.com/ https://crohnsmapvaccine.com/ https://crohnsmapvaccine.com/faq/ https://crohnsmapvaccine.com/faq/ Their idea is that Crohn's is caused by the bacterium mycobacterium avium subspecies paratuberculosis (or MAP for short). MAP has been proven to cause Johne's disease in cattle so the idea is that Crohn's is the same thing in people. They've started safety trials in patients with Crohn's. The next step is a wider trial to demonstrate efficacy.
- grumple 5y ago
  Pretty strange that there's one researcher listed and a dozen "social media / fund raisers". Suggests this isn't serious research and is instead a hype factory for acquiring money.
  - clouddrover 5y ago
    Sure. You've uncovered their dastardly plans.
  - keyanp 5y ago
    Unfortunately the lead researcher just passed away: https://www.kcl.ac.uk/news/in-memory-of-professor-john-hermon-taylor https://www.kcl.ac.uk/news/in-memory-of-professor-john-hermo... The actual clinical trial looks promising though: https://www.isrctn.com/ISRCTN36126048 https://www.isrctn.com/ISRCTN36126048
- odyssey7 5y ago
  So, a bacterium called Y. pseudotuberculosis is suspected in the paper at the top of this thread, and one called M. avium ssp. paratuberculosis is suspected by the group at your link.
b112 5y ago
Refrigeration has also enabled extremely long shipping chains for produce. My grandparents bought everything local, or grew their own. They canned, and preserved their own food too. Meat was the same too. Local bought and butchered. Now things are shipped tens of thousands of kilometers, and many vegetables and fruits are picked pre-ripe, so they will survive the journey. It could be cold-evolved bacteria. But it could also be that now, we are exposed to many orders more bacteria, than before. What human in the past, ate an orange from Isreal, cheese from Australia, almonds from California, meat from Alberta, broccoli from Mexico, onions from South America, while living in Canada, at the same meal?! In the old days, everything you ate was local, either from preserved or local stores (grain silos, etc). So all the bacteria you ate was local as well.
- chiefalchemist 5y ago
  > It could be cold-evolved bacteria. But it could also be that now, we are exposed to many orders more bacteria, than before. I'm not a doctor but I do gravitate to reading about gut bacteria. It's fascinating. It also seems to be fragile, there's a delicate balance. With that said, aside from some bacteria evolving to survive refrigeration, perhaps there is also "converse" bacteria that did not evolve? So the balance that we would get from local non-refrigerated meat doesn't really exist now? Freezers are changing the bacterial composition (as opposed to say the chemical composition). It's not what we're getting more of, but also less of. Maybe? Edit Just saw this listed on HN https://www.economist.com/science-and-technology/microplastics-in-household-dust-could-promote-antibiotic-resistance/21806204 https://www.economist.com/science-and-technology/microplasti...
  - b112 5y ago
    This is the true problem, in that, with so much change, it could be 10 problems. Person A has 1,4, and 9 as a problem with said symptoms, and so on..
hi41 5y ago
I am glad this topic came up. My son was diagnosed for Crohn's disease last year. He was 11 years at that time. His CalProtectin was 1040 at that time which very high compared to the safe value of 60. We gave him gluten free diet and it came down to 300 in 3 months but shot back to 700 few months later. Not sure what caused it go up. I am desperately seeking help in curing him of Crohn's. We are from India settled in USA. Does anyone have any good resources on this topic. The doctor said that first generation immigrants don't get this disease but they have noticed that the their kids do get it.
- fnord77 5y ago
  I have severe crohn's. Humira worked great for me for several years with no side effects that I was aware of. I was leery of biologics for several years, but I now regret not going on them sooner.
- unclekev 5y ago
  > I am desperately seeking help in curing him of Crohn's. There's no known cure for Crohn's disease, only treatment to reduce symptoms. If you are really lucky it might go into long-term remission, but theres no 'cure' yet. As someone who's been dealing with severe chronic symptoms of Chron's my whole life.... I wish there was.
  - CWuestefeld 5y ago
    unclekev is correct. I was diagnosed when I was ~12, over 40 years ago, and still have it. But despite the fact that there's no cure, there is a lot you can do to control it: * There are a lot more, better treatments today than back when I was a kid. Your GI doctor should be able to help with this. * I believe that the largest aggravator is stress. Your boy really needs to learn to handle stress. In my case, I was rather a perfectionist, and had to learn to just let go of things that I couldn't directly fix myself. And of course the disease itself is a prime stressor, so he's got to come to terms with it. * Different foods can be triggers for different people, due to individual differences plus the areas of the GI tract that are implicated. You need to experiment (keep a journal!) to figure out what these are. Don't fall for someone trying to sell a silver bullet like gluten-free. That may, indeed, help some people, but it won't others.
MrWiffles 5y ago
Possibly of interest to some: the bacteria that caused the various Black Plague pandemics over time is in the same family: yersinia pestis.
- Vetch 5y ago
  The paper notes as much: > Since Y. pseudotuberculosis is genetically very similar to Y. pestis, we hypothesised that NOD2 mutations may have provided a survival advantage to mutation carriers in the past during plague epidemics. As supposed, the current frequencies of CD-associated NOD2 mutations [ie, in the offspring of plague survivors] are correlated with the intensity of past Y. pestis epidemics in European and Mediterranean countries.
overton 5y ago
I have to wonder what other unintended side effects of modern tech/modes of behaviour we'll find.
ReptileMan 5y ago
Here are some other things that correlate with advent of the refrigeration (btw - people in Europe and Northern US had always had ample access to refrigeration - in big parts half of the year in a cellar the temperature will be below 10 degrees C). Reduction in fermented foods - with fresh produce all year round - stuff like sourkraut becomes a flavor agent and not a staple. Ditto with all other kinds of lactobacilic pickling. The rise of the dry yeast, mighty kitchen aid at home and the industrial bread at scale - In the dry yeast the ratio of yeast to lactobacilli is different than in cake yeast (and cake yeast if often inferior compared to sourdough starter when it comes to bio variety) The mixer (and chorleywood) at scale allows for faster dough development - and usually the recipes for home are insane - something like 7g of dry yeast for 500 g of flour - it pumps it full of air fast (2h), but you have more gluten that is often not chopped enough by protease action and the bacteria. The traditional home bread making was overnight proof. Also the flours today are much stronger than before so we get more gluten with them. And because wheat gluten is very useful - it is often added in all kinds of processed foods. Top that with what I frankly consider abuse in both human and animal populations that probably are not terribly beneficial to people gut biome and variety. And all this starts at the same time the refrigeration got going. And industrial bread is roll of the dice - it may vary from really good to cardboard. But the cardboard seems to be way more popular.
DoreenMichele 5y ago
CD is definitively associated with the occidental modern way of life 3. If the cold chain hypothesis is valid, the emergence of CD must be parallel to the development of industrial and domestic refrigeration. Figure 1A compares the annual incidence of the disease and the household equipment rate in several countries. There is a temporal correlation between these variables. It should be noted, however, that in a given country the disease begins to be detectable not at the time when refrigerators begin to be sold, but only when about 50% of households are equipped. This observation is counter-intuitive. It's an interesting hypothesis and I like the thinking. We need more of this kind of investigation. The problem I see is that refrigeration should reduce the incidence of food poisoning and malnutrition generally and generally improve survivability of vulnerable populations. So one possibility is that people who used to die mysteriously in early childhood are now living long enough to be diagnosed with various ailments. In other words, maybe modern life does cause Crohn's or maybe it just lets such people survive and get diagnosed and learn to live with their condition.
- sporedro 5y ago
  This reminds me of what I read about Nicotine and how it was thought to prevent Alzheimer's, but I believe it was just the fact those smoking tobacco had a lower chance to live to the age to be diagnosed or develop it.
  - ralusek 5y ago
    Motorcycles prevent old age.
    - smokeyfish 5y ago
      Old age prevents older age.
      - ralusek 5y ago
        Birth is the leading cause of death.
  - 5y ago
civilized 5y ago
Anybody else notice the typo in the first figure? The axis has 1940 where 1970 should be. Normally not noteworthy but funny to see 1940s twice on the x axis, and... how does this happen? Do people manually type their axis labels or something?
lr4444lr 5y ago
A correlation, you say? https://behindlabdoors.com/content/images/2015/Nov/chart.jpeg https://behindlabdoors.com/content/images/2015/Nov/chart.jpe...
geerlingguy 5y ago
As someone with Crohn's (diagnosed at 17, now have an ostomy), I often see a lot of conflation with IBS, which IBD is most definitely not. It's interesting, I've been part of some research studies, I've been through a number of surgeries, and I've literally tried every medical treatment that's available (and a couple that may be someday...) with some very good IBD research docs. And I've also seen that diet and lifestyle choices can definitely affect the severity of a flare, especially the feelings and symptoms. But they cannot 'cure' Crohn's or put it in remission. I currently have inflammation in my mouth, and unfortunately you can't just slice it out to take care of the problem like you can parts of the gut ;) Anyways, all that to say these studies come and go, a few have a sliver of promise or offer some new route for a researcher to go, but in my few decades of Crohn's experience, I've grown to accept that short of a very significant stroke of luck, there probably won't be a cure in my lifetime. And if there is, it'll probably crack the nut on a ton of other autoimmune diseases too. Hopefully!
- rp1 5y ago
  Just curious: have you tried infecting yourself with parasitic worms that suppress your immune system? That always sounded pretty cool…
  - mushtar 5y ago
    Yes, I have tried that with hookworms.
    - rp1 5y ago
      How did it go? A friend of my was investigating it for a condition he has.
- nanonomad 5y ago
  Have you tried giving things time off to heal with an elemental diet? It wasn't pleasant, but I survived off powdered amino acids, oil capsules, honey and cocoa for a couple months. The commerical/hospital preparations are for tube feeding patients and outrageously expensive. Look into nicotinic acid, a form of niacin. The "flushing" one. If you supplement with it start slow, get used to the burning sensation. It goes away after a few times. Avoid biologics unless you absolutely have to
mrtnmcc 5y ago
Why can't they just test this hypothesis that Yersinia bacteria growing under refrigeration cause the symptoms? Simply culture a small amount of Yersinia, spread it on a cracker and give it to a Chrohn's suscetiple person (and also placebo) and repeat with non-Chrohn people. The disease tends to have quick flare ups, so it should be easy to quickly draw a conclusion (unless they don't think flares are directly related).
- epgui 5y ago
  It's almost guaranteed to not be caused by Yersinia exclusively. Many whole-microbiome sequencing studies have been done, and this would have come up if it were that simple. More likely, a mix of Yersinia and other species will be selected for. It does raise novel ideas for how to work with and interpret microbiome studies. I'd like to see microbiota in fecal samples be sequenced before and after a cold test, for example. But even then, you might not see any results. It could be a metabolomic problem more than a microbiome problem, or even more likely still, both combined with an immune repertoire problem and other dysregulations.
interfixus 5y ago
Tangential, I know, but my mother-in-law, who has suffered heavily from Crohn's since her younger days, last week turned 100 with fabulously flying colours; mobile, mentally fit and could easily pass as a wellpreserved 80. The Crohn's is still there, of course, but kept in reasonable medical check. End of anecdote.
pubby 5y ago
I have crohns disease. Many people with my disease report improvement or even remission with specialized diets, but what's interesting is how disjoint these diets are. Some people eat only meat, others only vegan, others high-fiber, others low-fiber, and so on. The only similarity I can draw between these diets is that they greatly restrict the variety of food eaten. It makes me wonder if the modern practice of eating a variety of foods is harmful to our gut biome. I reckon variety results in constantly changing bacteria bloom/die-off scenarios. The blooms cause immune response flare-ups and accelerate bacterial evolution, while the die-offs cause extinctions, reducing the variety of our gut biomes. Anyway, this is just an armchair hypothesis, but I'm curious to hear if anyone has thoughts on it. I note that it fits the story of Crohns being a modern "first-world" disease, as for most of history humans ate the same few foods everyday, just as animals do. tl;dr: eating everything in moderation may be terrible advice
- _9omd 5y ago
  This is a really interesting point, and something I've pondered before. Bacterial die off can be particularly bad because Lipopolysaccharide (LPS), a form of endotoxin, is released from the membranes of the dead bacteria and can potentially find its way into the bloodstream if the tight junctions in the gut are compromised (ie: intestinal permeability / leaky gut). LPS is implicated in many (maybe most) autoimmune conditions, heart disease, non alcoholic liver disease, and a host of other conditions. If a constantly changing diet is causing regular shifts in the microbiome, this would cause regular bacterial dieoff events, and potentially regularly elevated LPS in the bloodstream. It would seem logical that the ideal situation in the gut is a diverse and stable microbiome. Which makes sense if you use ecology as a comparison, where something like an apex forest is both stable and diverse. And this is made possible because it has a very slow changing set of energy inputs. If the soil composition was constantly changing in a forest, there would be regular events of trees dying off and getting replaced with less mature species, resulting in both less stability and diversity. The land would also be likely to get overtaken by invasive species, as you can observe on patches of land that are routinely disturbed, like the side of a highway. I can't find the link right now, but a fascination of mine has been all potato diets (the potato hack). One guy who did this (or maybe there was a study) tested his microbiome before and after, and the after test showed a much healthier balance of species and a greatly increased diversity. At the time I remember being surprised by the increased diversity, as I, like most people, assume greater diversity of food would result in a greater diversity of bacterial species. But I have to imagine that a general characteristic of diverse diets is that they're not very stable. If someone is eating 100 different foods, it's unlikely they eat all of those 100 every day, so there is a constantly changing input to the gut, which would make for a constantly changing bacterial colony, which in theory would result in reduced diversity and regular dieoff events. This all makes a lot of sense too if you think about hunter gatherers and early agricultural peoples. They may have eaten a large number of plants and animals in the course of a year, but I imagine their diet would have rotated very slowly. So maybe they're foraging or growing a few things one month and that comprises the majority of their diet for a month or two. Then new things come into season and the diet shifts, and the microbiome shifts with it. This is much more stable than us modern humans that eat Thai food on monday, burgers on Tuesday, Mexican on Wednesday, and then Salad on Thursday when we're feeling bad about our food choices. It's only in the modern age with long distance shipping and refrigeration that we've had the luxury of changing our diets on the daily. Is this abundance of choice killing our guts? I think I'm going to experiment with a simple diet to see if it can fix my gut issues (IBS, maybe SIBO). An all potato diet seems too boring, but I think I can handle potato, steak, and broccoli, which sounds pretty similar to a bodybuilder's diet. A ratio of 6:2:1 by weight (potato:broccoli:steak) meets all nutritional requirements, other than coming in a tad low in calcium. Daily intake of 60oz potatoes, 20oz broccoli, 10oz sirloin steak, and 1/2 tsp calcium carbonate satisfies all dietary requirements and clocks in at 2200 calories.
kumarvvr 5y ago
I am from India, where for centuries, stored food was considered poisonous. Even a decade ago, in-spite of wide availability of refrigerators, most households never ate stored food, even if it was only for a few hours. The exceptions being pickle and powders (Many Indian cuisines have items that are fried and ground lentils and spices, a very common food and are made and stored for 6 months to a year) Things are changing now though. Junk food (Pizzas, burgers, etc) which consists mostly of frozen ingredients that are processed, a change in lifestyle leading to lack of time to prepare meals at home, etc have led to increased consumption in processed foods.
- tsol 5y ago
  Totally anecdotal-- as someone of Indian culture living in America, I'm convinced there's something in it that the American diet lacks. The longer a stretch of time I eat the american diet for more I get vague stomach trouble and a feeling of unwellness. But then I eat a nice spice filled curry with some rice and I suddenly feel great. I almost exclusively eat Indian food now as it's one of the only types of foods that prevents my stomach troubles. Some other foods like Pho also seem to treat me very well. It could be a lot of things-- less user of processed oils, lack of gluten, lack of artificial ingredients, etc. I'm not quite sure exactly what it is
easytiger 5y ago
Yersinia presumably multiplies adequately at a wide range of temperatures? Are there papers on its doubling in cold storage Vs pantry storage?
zuj 5y ago
(Haven't gone through the whole paper) Does this apply to folks suffering from IBS as well ? Or is it better to avoid extremely refrigerated food to be sure ?
dm319 5y ago
Have to be careful of incidence data over time. A lot has changed in the way we define diseases, as well as how we investigate them, from the point at which you see a general practitioner to whether you would get an endoscopy, to how the disease is defined histologically.
nvarsj 5y ago
It’s remarkable to me how little progress there has been in a scientific understanding of the gut. Why does it avoid understanding by modern science? My own experience is one of life long IBS. The worst I had it was in university, where I was in such intense abdominal pain I basically lay on my couch in cold sweats for a month straight unable to move and barely eating. Even with strong painkillers the pain was only slightly numbed. Gastros at UCSD couldn’t figure it out, had barium xrays, all the various escopies and they had no clue what was going on. Finally they wanted to perform surgery to have a look but all pain went away right before the surgery was scheduled. So bizarre.
sleepysysadmin 5y ago
Interesting idea, but very difficult to account for so many other major factors. First time i've read about the https://en.wikipedia.org/wiki/Yersinia https://en.wikipedia.org/wiki/Yersinia idea. Flipside, I feel like the theory is just finding a sideline relationship. Early 1900s had so many major experiments start happening. Refrigerants is only 1 of them. How about major new pesticides? How about a major shift from eating animals to plants? We also have similar discovery of obesity growing about the same rate. There's a clear and obvious relationship here. Everything is food related. So what happens if you simply reverse what changed in the last 100 years. Try carnivore and after some adjustment period your crohns goes away. As you reintroduce plants into your diet, crohns symptoms return.
zuj 5y ago
After suffering from mild IBS, time and again I get reminded how important gut health is. It is definitely the core of the immune system. Screw up the gut health it will lead to all sorts of ailments.

276 points by fnord77 5y ago

Surely that correlates with a bunch of other stuff though like advent of processed food?

Correlation between better living standards/food quality/medicine and people living with diseases that used to be fatal.

ineedasername 5y ago

It seems like a lot of this is equally explainable as better diagnosis, meaning CD could have been around at similar rates much longer but medical science just didn't diagnose it as such or at the same rates. It's a question you always have to ask when you see an increase in, well, most things: Is it an actual increase, or are we just better at noticing it now?

abhisuri97 5y ago
Surprised this isn't higher up. Crohn's was formally named/created as its own clinical entity in 1932 and the paper shows one of its graphs (Fig 1) starting in the 1940s. I doubt 8 years was enough for awareness to get out to the entire physician community about the existence of the disease and there were probably a lot of misdiagnosed cases in its early days (since crohn's has a clinically diverse presentation).
commentsgaloer2 5y ago
Anecdote of course, but my personal case may support this claim. My grandfather died when he was 34 (1960's) from an intestinal ulcer. Not diagnosed with anything. Born in south America but from Jewish immigrants (relevant as I've been told Crohn's is more prevalent among Jewish people) I was diagnosed with Crohn's when I turned 31, after having a colonoscopy because of severe diarrhea. Humira's been working so far, I've been on it for 2 years after other meds didn't do the trick. Edit: just in case it wasn't clear: I also had a pretty big intestinal ulcer. But getting diagnosed helped it not get worse, and after going on humira, it eventually got better

moralestapia 5y ago

Before some "wise guy" comes to parrot about how "correlation does not imply causation" [1], please, take some time to read the article as it has some valuable information. [1]: We've all heard that already, it doesn't impress anyone anymore.

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uniqueuid 5y ago
And it's not even in the article title. In fact, the text says " Figure 1A compares the annual incidence of the disease and the household equipment rate in several countries. There is a temporal correlation between these variables." A temporal correlation is something entirely different to a cross-sectional correlation (arrow of time etc.)
- DantesKite 5y ago
  I tried researching what a temporal correlation is. Do you have short explanation for it?
  - uniqueuid 5y ago
    Temporal correlations are a family of things, since there are many degrees of freedom to choose what to compare with what. A very simple test is the "Granger Causality", which tests whether one timeline significantly predicts another one. You can formulate more complex models such as time series a predicting b with a certain lag. Ultimately, the idea is most often to remove unrelated factors (such as control variables, seasonality, self-influence i.e. autoregression) and then measure how well one series at t(0) predicts another one at t(1), while optionally doing some sort of hyperparameter optimization for the lag (i.e. determine which lag works best).
    - DantesKite 5y ago
      Thank you. Much appreciated.

teeray 5y ago

I wonder if anyone has tried a treatment with a non-refrigerated diet EDIT: I read some more and found “Nutritional treatment of CD was first proposed by Voitk in 1973. The treatment consists of administering a specific liquid formula…” It doesn’t say if that formula is refrigerated or not. My assumption is that it isn’t because it’s cited here, but that is an assumption.

uniqueuid 5y ago
Right, this is what the authors demand: "as no single experiment can definitively confirm the theory, we must continue to test it with additional works. Among them [and even if insufficient to definitively validate the hypothesis], a randomised clinical trial comparing patients with low versus high exposure to Yersinia would be an important step."
teruakohatu 5y ago
Essentially they found that tube fed diets do help, and they are effectively refrigeration free. > "Furthermore, no specific foodstuff has been incriminated in CD, and combining enteral nutrition with a highly controlled oral diet was recently shown to be effective" ... "It should be noted, however, that enteral nutrition effectively excludes refrigerated foods." They go on to say that enteral nutrition differ from regular diets so that the mechanism that make them work may not to the fact that they are unrefrigerated. A refrigeration free diet would not be impossible today, but hard. Given he prevalence of this bacteria today, non-electric cold stores would probably also need to be removed from the supply chain, making even a pre-industrial Western diet problematic. A sufficiently cooked vegan diet, minus everything that causes problems with people that suffer from Crohn's Disease, maybe would work? Ideally with vegetables that have not been refrigerated. Winter would be pretty bleak.
- rini17 5y ago
  Pre-industrial western diet cold stored food was either salted (meat), fermented (cabbage, cheese) or alive (fruit, root vegetables, potatoes)...so, it's possible there was completely different microbiology than in modern processed food.

tomrod 5y ago

This is a bad title. Other trends since 1910 (the last 110 years) - Electromagnetic wave use increase via radio, television, cell and internet, and microwaves - Maximum altitude humans have reached - Number of bodies on Everest - Increase in pounds of enriched uranium and available thorium - Increase in the number of people who have read work by Ursula K. Le Guin and Isaac Asimov None of these have causal implications. But the article does connect a qualitative theory and show correlation -- suggesting the hypothesis could be a thread to chase down. This is the key thesis: > According to the cold chain hypothesis, the development of industrial and domestic refrigeration has led to frequent exposure of human populations to bacteria capable of growing in the cold. These bacteria, at low levels of exposure, particularly those of the genus Yersinia, are believed to be capable of inducing exacerbated inflammation of the intestine in genetically predisposed subjects. EDIT: Title: Crohn’s Disease: Is the Cold Chain Hypothesis Still Hot? Abstract: > Crohn’s disease [CD] is an inflammatory bowel disease of unknown aetiology. During recent decades, significant technological advances led to development of -omic datasets allowing a detailed description of the disease. Unfortunately these have not, to date, resolved the question of the aetiology of CD. Thus, it may be necessary to [re]consider hypothesis-driven approaches to resolve the aetiology of CD. According to the cold chain hypothesis, the development of industrial and domestic refrigeration has led to frequent exposure of human populations to bacteria capable of growing in the cold. These bacteria, at low levels of exposure, particularly those of the genus Yersinia, are believed to be capable of inducing exacerbated inflammation of the intestine in genetically predisposed subjects. We discuss the consistency of this working hypothesis in light of recent data from epidemiological, clinical, pathological, microbiological, and molecular studies.

deleted 5y ago
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jessriedel 5y ago
Your first point is misaimed. They don't just note the historical worldwide rise in refrigeration goes along side a worldwide rise in Chrohn's. They compare the timing for Chrohn's and refrigeration for different demographic groups in different countries and even, if I am reading this correctly, at the level of individuals. The other things you list will not vary in the same way at that level of detail, although one must of course be wary of multiple hypothesis testing, forking paths, etc.

DantesKite 5y ago

It wouldn't surprise me if refrigeration contributes to the development of Crohn's disease. The causes can be multi-variate and anecdotally, from my own research, microbes (yeast, bacteria, fungi) all seem to play a key role. Anything that disturbs the balance in pathogenic ways can lead to dysfunction, especially antibiotics, but also a lack of plant cell walls in our diets. Everybody is slightly different, not just genetically, but in terms of the diversity of bacteria. There have been a few people who have managed to put Crohn's disease into remissions with raw kefir produced at home (the ones at store are not comparable) as well as with Visbiome, a probiotic produced in the lab with many studies behind it. And I've also heard the carnivore diet for short durations may help. There doesn't seem to be a consistent way to treat Crohn's disease and obviously, medicine to control flares is a must if the situation demands it. It does seem like a great many gut and autoimmune issues are somehow related to the diversity of microbes though and I look forward to more clinical research like this. We need all the help we can get.

bladegash 5y ago
Likewise on the welcoming of any bit of research! I ended up in the hospital about a year ago and found out it was the result of Crohn’s (34 years old). Another hospitalization, countless diet attempts, medications, and biologics, finally found something that worked, other than prednisone. If there is one thing I realized, it is that the effectiveness of treatments really is dependent on each individual’s biology. Possible foods that trigger me were completely fine for others I had spoken with, and vice versa. It’s encouraging to see as much research as there is and makes me hopeful not just for myself, but for others with the same condition (many who have it far worse than me).
- jcrben 5y ago
  I got Crohn's about the same age (34). A couple years later at 36 I'm now on better health than I've ever been. I responded well to a biologic (vedolizumab aka Entyvio). But I also did exclusive enteral nutrition for months concurrently to help push me the edge. These days I eat a lot of sweet potatoes and chicken, with relatively little processed food. I also feel like theracurmin helps me https://pubmed.ncbi.nlm.nih.gov/32412598/ https://pubmed.ncbi.nlm.nih.gov/32412598/

emmelaich 5y ago

Good paper. If true I wonder how it could be combatted effectively. It's hard to do without refrigeration. Perhaps its related mainly to fast food, where the consistent refrigeration is less sure. CD has also been associated with Mycobacterium paratuberculosis, because that is implicated in the similar Jahne's disease in cattle and sheep: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894645/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894645/ Lastly, I also wonder if refrigeration has a role to play in Multiple Sclerosis. It also has strong relations with modern lifestyle and latitude (temperature). The suspect virus in the MS case seems to be https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus https://en.wikipedia.org/wiki/Epstein%E2%80%93Barr_virus aka mononucleosis / glandular fever.

laurent92 5y ago
> It's hard to do without refrigeration. We’ve changed our diet since refrigeration is available. That’s an argument of vegetarians: Since we want meat, we need a refrigerator, which in turn makes us eat a lot of processed food. Frozen food, yoghurts, milk-based products, all of those are heavily processed, we try to “fill in the rest of the fridge”. My vegetarian friends reversed it: Eat veggies and fruits in quantity, grains, nuts, beans, bread, spices, oils… I’m a meat eater but I’m just passing the word: It is possible to live without refrigeration without compromising food, except meat.
- cerved 5y ago
  I don't know, refrigeration seems pretty useful
- Spivak 5y ago
  Every vegetarian but not vegan I know, including myself, eats dairy like crazy so I cant really say I experience this sentiment. Also fruits and veggies are basically the definition of food that needs refrigeration or “processing” for preservation. Strawberries that aren’t specifically bread to be hearty can spoil in less than a day. Prior to refrigeration we leaned on (and probably still do if you have a garden) canning, drying, pickling, fermenting — I mean making garlic confit was originally a way to preserve garlic. And you can preserve meat fine without refrigerators, that’s why we started salting, smoking and curing meat. The thing you compromise without a refrigerator is the ability to have truly fresh fruits, veggies, and meat for longer than the natural spoiling time.

lifeisstillgood 5y ago

There are a surprisingly large number of changes since ~1900 that have had big environmental effects on "modern life" that we are barely getting to grips with - this cold chain one is new to me but it fits in with electric lighting, urban noise and air pollution and even mass literacy etc as massive changes we can barely get to grips with I am deffo not arguing for some return to some paeleo, noble savage ideal. But our poor bodies evolved for something very different to eating burgers on a plane under flourescent lighting whilst reading text on a screen. Whatever we build as societies in the next 100'years, we should build at human scale.

number6 5y ago
Our bodys evolved to survive under harsh conditions until our offsprings are old enough to carry on (30 - 40 years) everything on top is bonus. Evolution and Biology have no agency. There is no moral, no right kind of living. If you procreate you fulfilled your biological "destiny". You can do that under eating a burger on a plane while reading on a screen. Evolution doesn't mind. Our bodys don't mind. Warrenty runs out in your thirties. Good thing we have brains that allow us to prolong our life's and increase our well-being.
- deleted 5y ago
  [deleted]
- rp1 5y ago
  I don’t think the GP was arguing that “evolution cares”. Rather, I think they were saying that we evolved as part of a system that moved at a certain speed. Changes to that system were reflected as part of the evolutionary feedback mechanism. Now, however, we’re changing the system so fast, evolution has no hope of keeping up.
- enchiridion 5y ago
  Our brains were evolved.
- ricardobeat 5y ago
  Well, clearly something goes wrong as children also get these debilitating diseases.

clouddrover 5y ago

This research group is developing a therapeutic Crohn's vaccine: https://crohnsmapvaccine.com/ https://crohnsmapvaccine.com/ https://crohnsmapvaccine.com/faq/ https://crohnsmapvaccine.com/faq/ Their idea is that Crohn's is caused by the bacterium mycobacterium avium subspecies paratuberculosis (or MAP for short). MAP has been proven to cause Johne's disease in cattle so the idea is that Crohn's is the same thing in people. They've started safety trials in patients with Crohn's. The next step is a wider trial to demonstrate efficacy.

grumple 5y ago
Pretty strange that there's one researcher listed and a dozen "social media / fund raisers". Suggests this isn't serious research and is instead a hype factory for acquiring money.
- clouddrover 5y ago
  Sure. You've uncovered their dastardly plans.
- keyanp 5y ago
  Unfortunately the lead researcher just passed away: https://www.kcl.ac.uk/news/in-memory-of-professor-john-hermon-taylor https://www.kcl.ac.uk/news/in-memory-of-professor-john-hermo... The actual clinical trial looks promising though: https://www.isrctn.com/ISRCTN36126048 https://www.isrctn.com/ISRCTN36126048
odyssey7 5y ago
So, a bacterium called Y. pseudotuberculosis is suspected in the paper at the top of this thread, and one called M. avium ssp. paratuberculosis is suspected by the group at your link.

b112 5y ago

Refrigeration has also enabled extremely long shipping chains for produce. My grandparents bought everything local, or grew their own. They canned, and preserved their own food too. Meat was the same too. Local bought and butchered. Now things are shipped tens of thousands of kilometers, and many vegetables and fruits are picked pre-ripe, so they will survive the journey. It could be cold-evolved bacteria. But it could also be that now, we are exposed to many orders more bacteria, than before. What human in the past, ate an orange from Isreal, cheese from Australia, almonds from California, meat from Alberta, broccoli from Mexico, onions from South America, while living in Canada, at the same meal?! In the old days, everything you ate was local, either from preserved or local stores (grain silos, etc). So all the bacteria you ate was local as well.

chiefalchemist 5y ago
> It could be cold-evolved bacteria. But it could also be that now, we are exposed to many orders more bacteria, than before. I'm not a doctor but I do gravitate to reading about gut bacteria. It's fascinating. It also seems to be fragile, there's a delicate balance. With that said, aside from some bacteria evolving to survive refrigeration, perhaps there is also "converse" bacteria that did not evolve? So the balance that we would get from local non-refrigerated meat doesn't really exist now? Freezers are changing the bacterial composition (as opposed to say the chemical composition). It's not what we're getting more of, but also less of. Maybe? Edit Just saw this listed on HN https://www.economist.com/science-and-technology/microplastics-in-household-dust-could-promote-antibiotic-resistance/21806204 https://www.economist.com/science-and-technology/microplasti...
- b112 5y ago
  This is the true problem, in that, with so much change, it could be 10 problems. Person A has 1,4, and 9 as a problem with said symptoms, and so on..

hi41 5y ago

I am glad this topic came up. My son was diagnosed for Crohn's disease last year. He was 11 years at that time. His CalProtectin was 1040 at that time which very high compared to the safe value of 60. We gave him gluten free diet and it came down to 300 in 3 months but shot back to 700 few months later. Not sure what caused it go up. I am desperately seeking help in curing him of Crohn's. We are from India settled in USA. Does anyone have any good resources on this topic. The doctor said that first generation immigrants don't get this disease but they have noticed that the their kids do get it.

fnord77 5y ago
I have severe crohn's. Humira worked great for me for several years with no side effects that I was aware of. I was leery of biologics for several years, but I now regret not going on them sooner.
unclekev 5y ago
> I am desperately seeking help in curing him of Crohn's. There's no known cure for Crohn's disease, only treatment to reduce symptoms. If you are really lucky it might go into long-term remission, but theres no 'cure' yet. As someone who's been dealing with severe chronic symptoms of Chron's my whole life.... I wish there was.
- CWuestefeld 5y ago
  unclekev is correct. I was diagnosed when I was ~12, over 40 years ago, and still have it. But despite the fact that there's no cure, there is a lot you can do to control it: * There are a lot more, better treatments today than back when I was a kid. Your GI doctor should be able to help with this. * I believe that the largest aggravator is stress. Your boy really needs to learn to handle stress. In my case, I was rather a perfectionist, and had to learn to just let go of things that I couldn't directly fix myself. And of course the disease itself is a prime stressor, so he's got to come to terms with it. * Different foods can be triggers for different people, due to individual differences plus the areas of the GI tract that are implicated. You need to experiment (keep a journal!) to figure out what these are. Don't fall for someone trying to sell a silver bullet like gluten-free. That may, indeed, help some people, but it won't others.

MrWiffles 5y ago

Possibly of interest to some: the bacteria that caused the various Black Plague pandemics over time is in the same family: yersinia pestis.

Vetch 5y ago
The paper notes as much: > Since Y. pseudotuberculosis is genetically very similar to Y. pestis, we hypothesised that NOD2 mutations may have provided a survival advantage to mutation carriers in the past during plague epidemics. As supposed, the current frequencies of CD-associated NOD2 mutations [ie, in the offspring of plague survivors] are correlated with the intensity of past Y. pestis epidemics in European and Mediterranean countries.

overton 5y ago

I have to wonder what other unintended side effects of modern tech/modes of behaviour we'll find.

ReptileMan 5y ago

Here are some other things that correlate with advent of the refrigeration (btw - people in Europe and Northern US had always had ample access to refrigeration - in big parts half of the year in a cellar the temperature will be below 10 degrees C). Reduction in fermented foods - with fresh produce all year round - stuff like sourkraut becomes a flavor agent and not a staple. Ditto with all other kinds of lactobacilic pickling. The rise of the dry yeast, mighty kitchen aid at home and the industrial bread at scale - In the dry yeast the ratio of yeast to lactobacilli is different than in cake yeast (and cake yeast if often inferior compared to sourdough starter when it comes to bio variety) The mixer (and chorleywood) at scale allows for faster dough development - and usually the recipes for home are insane - something like 7g of dry yeast for 500 g of flour - it pumps it full of air fast (2h), but you have more gluten that is often not chopped enough by protease action and the bacteria. The traditional home bread making was overnight proof. Also the flours today are much stronger than before so we get more gluten with them. And because wheat gluten is very useful - it is often added in all kinds of processed foods. Top that with what I frankly consider abuse in both human and animal populations that probably are not terribly beneficial to people gut biome and variety. And all this starts at the same time the refrigeration got going. And industrial bread is roll of the dice - it may vary from really good to cardboard. But the cardboard seems to be way more popular.

DoreenMichele 5y ago

CD is definitively associated with the occidental modern way of life 3. If the cold chain hypothesis is valid, the emergence of CD must be parallel to the development of industrial and domestic refrigeration. Figure 1A compares the annual incidence of the disease and the household equipment rate in several countries. There is a temporal correlation between these variables. It should be noted, however, that in a given country the disease begins to be detectable not at the time when refrigerators begin to be sold, but only when about 50% of households are equipped. This observation is counter-intuitive. It's an interesting hypothesis and I like the thinking. We need more of this kind of investigation. The problem I see is that refrigeration should reduce the incidence of food poisoning and malnutrition generally and generally improve survivability of vulnerable populations. So one possibility is that people who used to die mysteriously in early childhood are now living long enough to be diagnosed with various ailments. In other words, maybe modern life does cause Crohn's or maybe it just lets such people survive and get diagnosed and learn to live with their condition.

sporedro 5y ago
This reminds me of what I read about Nicotine and how it was thought to prevent Alzheimer's, but I believe it was just the fact those smoking tobacco had a lower chance to live to the age to be diagnosed or develop it.
- ralusek 5y ago
  Motorcycles prevent old age.
  - smokeyfish 5y ago
    Old age prevents older age.
    - ralusek 5y ago
      Birth is the leading cause of death.
- 5y ago

civilized 5y ago

Anybody else notice the typo in the first figure? The axis has 1940 where 1970 should be. Normally not noteworthy but funny to see 1940s twice on the x axis, and... how does this happen? Do people manually type their axis labels or something?

lr4444lr 5y ago

A correlation, you say? https://behindlabdoors.com/content/images/2015/Nov/chart.jpeg https://behindlabdoors.com/content/images/2015/Nov/chart.jpe...

geerlingguy 5y ago

As someone with Crohn's (diagnosed at 17, now have an ostomy), I often see a lot of conflation with IBS, which IBD is most definitely not. It's interesting, I've been part of some research studies, I've been through a number of surgeries, and I've literally tried every medical treatment that's available (and a couple that may be someday...) with some very good IBD research docs. And I've also seen that diet and lifestyle choices can definitely affect the severity of a flare, especially the feelings and symptoms. But they cannot 'cure' Crohn's or put it in remission. I currently have inflammation in my mouth, and unfortunately you can't just slice it out to take care of the problem like you can parts of the gut ;) Anyways, all that to say these studies come and go, a few have a sliver of promise or offer some new route for a researcher to go, but in my few decades of Crohn's experience, I've grown to accept that short of a very significant stroke of luck, there probably won't be a cure in my lifetime. And if there is, it'll probably crack the nut on a ton of other autoimmune diseases too. Hopefully!

rp1 5y ago
Just curious: have you tried infecting yourself with parasitic worms that suppress your immune system? That always sounded pretty cool…
- mushtar 5y ago
  Yes, I have tried that with hookworms.
  - rp1 5y ago
    How did it go? A friend of my was investigating it for a condition he has.
nanonomad 5y ago
Have you tried giving things time off to heal with an elemental diet? It wasn't pleasant, but I survived off powdered amino acids, oil capsules, honey and cocoa for a couple months. The commerical/hospital preparations are for tube feeding patients and outrageously expensive. Look into nicotinic acid, a form of niacin. The "flushing" one. If you supplement with it start slow, get used to the burning sensation. It goes away after a few times. Avoid biologics unless you absolutely have to

mrtnmcc 5y ago

Why can't they just test this hypothesis that Yersinia bacteria growing under refrigeration cause the symptoms? Simply culture a small amount of Yersinia, spread it on a cracker and give it to a Chrohn's suscetiple person (and also placebo) and repeat with non-Chrohn people. The disease tends to have quick flare ups, so it should be easy to quickly draw a conclusion (unless they don't think flares are directly related).

epgui 5y ago
It's almost guaranteed to not be caused by Yersinia exclusively. Many whole-microbiome sequencing studies have been done, and this would have come up if it were that simple. More likely, a mix of Yersinia and other species will be selected for. It does raise novel ideas for how to work with and interpret microbiome studies. I'd like to see microbiota in fecal samples be sequenced before and after a cold test, for example. But even then, you might not see any results. It could be a metabolomic problem more than a microbiome problem, or even more likely still, both combined with an immune repertoire problem and other dysregulations.

interfixus 5y ago

Tangential, I know, but my mother-in-law, who has suffered heavily from Crohn's since her younger days, last week turned 100 with fabulously flying colours; mobile, mentally fit and could easily pass as a wellpreserved 80. The Crohn's is still there, of course, but kept in reasonable medical check. End of anecdote.

pubby 5y ago

I have crohns disease. Many people with my disease report improvement or even remission with specialized diets, but what's interesting is how disjoint these diets are. Some people eat only meat, others only vegan, others high-fiber, others low-fiber, and so on. The only similarity I can draw between these diets is that they greatly restrict the variety of food eaten. It makes me wonder if the modern practice of eating a variety of foods is harmful to our gut biome. I reckon variety results in constantly changing bacteria bloom/die-off scenarios. The blooms cause immune response flare-ups and accelerate bacterial evolution, while the die-offs cause extinctions, reducing the variety of our gut biomes. Anyway, this is just an armchair hypothesis, but I'm curious to hear if anyone has thoughts on it. I note that it fits the story of Crohns being a modern "first-world" disease, as for most of history humans ate the same few foods everyday, just as animals do. tl;dr: eating everything in moderation may be terrible advice

_9omd 5y ago
This is a really interesting point, and something I've pondered before. Bacterial die off can be particularly bad because Lipopolysaccharide (LPS), a form of endotoxin, is released from the membranes of the dead bacteria and can potentially find its way into the bloodstream if the tight junctions in the gut are compromised (ie: intestinal permeability / leaky gut). LPS is implicated in many (maybe most) autoimmune conditions, heart disease, non alcoholic liver disease, and a host of other conditions. If a constantly changing diet is causing regular shifts in the microbiome, this would cause regular bacterial dieoff events, and potentially regularly elevated LPS in the bloodstream. It would seem logical that the ideal situation in the gut is a diverse and stable microbiome. Which makes sense if you use ecology as a comparison, where something like an apex forest is both stable and diverse. And this is made possible because it has a very slow changing set of energy inputs. If the soil composition was constantly changing in a forest, there would be regular events of trees dying off and getting replaced with less mature species, resulting in both less stability and diversity. The land would also be likely to get overtaken by invasive species, as you can observe on patches of land that are routinely disturbed, like the side of a highway. I can't find the link right now, but a fascination of mine has been all potato diets (the potato hack). One guy who did this (or maybe there was a study) tested his microbiome before and after, and the after test showed a much healthier balance of species and a greatly increased diversity. At the time I remember being surprised by the increased diversity, as I, like most people, assume greater diversity of food would result in a greater diversity of bacterial species. But I have to imagine that a general characteristic of diverse diets is that they're not very stable. If someone is eating 100 different foods, it's unlikely they eat all of those 100 every day, so there is a constantly changing input to the gut, which would make for a constantly changing bacterial colony, which in theory would result in reduced diversity and regular dieoff events. This all makes a lot of sense too if you think about hunter gatherers and early agricultural peoples. They may have eaten a large number of plants and animals in the course of a year, but I imagine their diet would have rotated very slowly. So maybe they're foraging or growing a few things one month and that comprises the majority of their diet for a month or two. Then new things come into season and the diet shifts, and the microbiome shifts with it. This is much more stable than us modern humans that eat Thai food on monday, burgers on Tuesday, Mexican on Wednesday, and then Salad on Thursday when we're feeling bad about our food choices. It's only in the modern age with long distance shipping and refrigeration that we've had the luxury of changing our diets on the daily. Is this abundance of choice killing our guts? I think I'm going to experiment with a simple diet to see if it can fix my gut issues (IBS, maybe SIBO). An all potato diet seems too boring, but I think I can handle potato, steak, and broccoli, which sounds pretty similar to a bodybuilder's diet. A ratio of 6:2:1 by weight (potato:broccoli:steak) meets all nutritional requirements, other than coming in a tad low in calcium. Daily intake of 60oz potatoes, 20oz broccoli, 10oz sirloin steak, and 1/2 tsp calcium carbonate satisfies all dietary requirements and clocks in at 2200 calories.

kumarvvr 5y ago

I am from India, where for centuries, stored food was considered poisonous. Even a decade ago, in-spite of wide availability of refrigerators, most households never ate stored food, even if it was only for a few hours. The exceptions being pickle and powders (Many Indian cuisines have items that are fried and ground lentils and spices, a very common food and are made and stored for 6 months to a year) Things are changing now though. Junk food (Pizzas, burgers, etc) which consists mostly of frozen ingredients that are processed, a change in lifestyle leading to lack of time to prepare meals at home, etc have led to increased consumption in processed foods.

tsol 5y ago
Totally anecdotal-- as someone of Indian culture living in America, I'm convinced there's something in it that the American diet lacks. The longer a stretch of time I eat the american diet for more I get vague stomach trouble and a feeling of unwellness. But then I eat a nice spice filled curry with some rice and I suddenly feel great. I almost exclusively eat Indian food now as it's one of the only types of foods that prevents my stomach troubles. Some other foods like Pho also seem to treat me very well. It could be a lot of things-- less user of processed oils, lack of gluten, lack of artificial ingredients, etc. I'm not quite sure exactly what it is

easytiger 5y ago

Yersinia presumably multiplies adequately at a wide range of temperatures? Are there papers on its doubling in cold storage Vs pantry storage?

zuj 5y ago

(Haven't gone through the whole paper) Does this apply to folks suffering from IBS as well ? Or is it better to avoid extremely refrigerated food to be sure ?

dm319 5y ago

Have to be careful of incidence data over time. A lot has changed in the way we define diseases, as well as how we investigate them, from the point at which you see a general practitioner to whether you would get an endoscopy, to how the disease is defined histologically.

nvarsj 5y ago

It’s remarkable to me how little progress there has been in a scientific understanding of the gut. Why does it avoid understanding by modern science? My own experience is one of life long IBS. The worst I had it was in university, where I was in such intense abdominal pain I basically lay on my couch in cold sweats for a month straight unable to move and barely eating. Even with strong painkillers the pain was only slightly numbed. Gastros at UCSD couldn’t figure it out, had barium xrays, all the various escopies and they had no clue what was going on. Finally they wanted to perform surgery to have a look but all pain went away right before the surgery was scheduled. So bizarre.

sleepysysadmin 5y ago

Interesting idea, but very difficult to account for so many other major factors. First time i've read about the https://en.wikipedia.org/wiki/Yersinia https://en.wikipedia.org/wiki/Yersinia idea. Flipside, I feel like the theory is just finding a sideline relationship. Early 1900s had so many major experiments start happening. Refrigerants is only 1 of them. How about major new pesticides? How about a major shift from eating animals to plants? We also have similar discovery of obesity growing about the same rate. There's a clear and obvious relationship here. Everything is food related. So what happens if you simply reverse what changed in the last 100 years. Try carnivore and after some adjustment period your crohns goes away. As you reintroduce plants into your diet, crohns symptoms return.

zuj 5y ago

After suffering from mild IBS, time and again I get reminded how important gut health is. It is definitely the core of the immune system. Screw up the gut health it will lead to all sorts of ailments.