Researchers identify major driver of inflammatory bowel and related diseases
theguardian.com
theguardian.com
I started going to therapy as an adult and made a lot of progress in my mental health. I went off my medications 5 years ago and have been healthy since without intervention - I give a lot of credit to this work. I don't think we fully understand the role of the mind/emotions in health; my advice to anyone suffering from IBS and the like is not to forget the mind component to overall health. When you're suffering in your head, it can sometimes manifest in your body.
Gabor Maté talks a lot about this connection: https://www.youtube.com/watch?v=1fPQ7Oc44SU
After reading Pollan’s “How to Change your Mind” I have wondered if Psychedelics could be the answer to resetting pathways.
Pollan is great! I’d be happy to chat more with you - send me a PM.
I think it's absolutely universally accepted that stress is a major factor in autoimmune and inflammatory disease. Reducing stress by working on mental health definitely has the potential to reduce inflammation levels in some people to the point where you need no medication.
But like everything it's not a silver bullet.
Another weird/fascinating factor for me at least is that less convenient access to a toilet seems to correlate with less symptoms. When I'm hiking in the mountains I never seem to have a high frequency of needing to take a dump. I've often wondered if there is something of an explanation there for the rise in rate of Crohn's diagnosis in countries as they develop.
AFAIK I don't have Crohn's or any inflammatory issues, but boy is this an accurate description of me. My theory has always been that my need to use the bathroom was strongly correlated with coffee and food. When I'm home I'm constantly drinking coffee and snacking, when I'm away from home I'm not.
Just a speculation that came to me after reading the article. I could be wrong, but I would make a interesting test probably IMO.
Not Chron's but a related disease. For me the symptoms are strongly correlated with how embarrassing it would be if I had to go. So hiking in the mountains is pretty relaxed (unless it's a date or something), just find a spot off trail. In the chair at the dentist with instruments in your mouth and a bib on? All of a sudden I've gotta go.
Not to dismiss your observations but to supply an alternative explanation for your belief about them: Do you remember your embarrassing experiences vs the not embarrassing ones equally well? A selective memory can give the illusion of correlation. Moreover once you have some belief you may become better at finding and remembering confirming evidence for that belief.
I started having symptoms of colitis ulcerosa when I was 18 and had final high school exams. I was under tons of stress. I started to care much less about such things and had years-long remission. There were only 2 other flare-ups - when I was passing driving licence test, and when I had the first big series of exams at university.
Basically every time I drove myself very hard I had another episode. And it's not fun to suddenly shit yourself in public transport let me tell you :/
It's been over 20 years since last time I had colitis ulcerosa flare-up. But, in the meantime I was also diagnosed with autoimmune liver disease (PSC), and I'm not sure this one is stress-related. It seems to me it just ticks away at my liver and even very relaxed lifestyle doesn't help. I'm very hopeful about new drugs for this, as the only alternative seems to be to wait for inevitable liver transplant later in life.
Stomach ulcers were "stress related" until whoops: turns out it's H. Pylori infections, and can be cured easily with antibiotics.
My UC is entirely diet related.
A doctor friend and I think we have - as amateurs, mind: his specialty is very far from GI, but he reads and shares with me every UC paper that's published; I have no medical training, but am a motivated auto-didact on this subject - identified three or maybe four etiologies which are lumped together as "UC". The best gastro doc I've seen kinda shrugged, and said (roughly) "probably so, but they all respond to the same drugs in the same ways, so there's not much motivation to draw distinctions".
I'm not quite sure what to think about that answer. I do think it's good for patients to identify their own triggers.
Your endocrine system, sympathetic nervous system and central nervous system are all wired up together so of course changes/disfunctions in one can cause symptoms in another.
And there's lots of pathogens that cause "flu-like" symptoms, so it makes sense there could be multiple things that cause "UC-like" symptoms.
My doc says my crohns is inflaming the whole end part of my colon somewhat consistently; my small intestines are fine. Many other patients of hers have inflammations at specific parts that are more severe, and also sometiumes the small intestines are affected.
And then my PSC seems to (so far) only affect my small ducts; which doesnt mean it cant get more severe but so far is "less damaging" then "normal" PSC. No one seems to really know if these are the same disease, related or entirely different. Its kinda crazy tbh
Oh, also nicotine. I don't like being addicted to my vape pen, but a steady dose of nicotine gives me a much wider margin for error with my diet. Curiously, this connection was pointed out by my first, and best, gastro doctor: the two groups who present UC much less frequently than others are smokers and Ashkenazi jews. He told me that (prefaced by "I'm a doctor, so I can't really recommend this, but...) some of his patients found cigars helpful, and are fairly low-risk, as smoking goes. I used cigars for years to kill sub-clinical flares, before getting tired of the smell, and the time-commitment and hassle, and worried about the blood-pressure spikes they induce. Vaping is superior in every way, and I have made the cost-benefit wager that whatever (fairly low, so far as we can tell) health risk that comes with vaping is less than the risk and consequence of colon cancer from less-controlled UC.
That is, by the way, one of the big clues to varying etiologies: some people's UC is exacerbated, not helped, by nicotine. (My understanding is that Crohn's is always exacerbated.) My doctor friend and I believe we understand the mechanism behind why it works for my particular case.
I personally have Crohns and PSC as well, and I think less stress helped; but I am on Rinvoq (INN-Upadacitinib) and eat psyllium husks and still have occasional diarrhea, what helps A TON however is sport. I skateboard (and whenever I find the time I go HARD), and 1-2 days after I am always good, colon wise. When I dont skate for a week and eat slightly fatty i have problems, but when skate on a friday and then order opne of those disguting cheap pizzas from that greek place i am still good (i dont do this often but it happens).
Why I have these autoimmun diseases is also an interesting question. My biological parents are both good in that regard, so is my extended family. However I do know my bio-mom smoked while pregnant, and i passively smoked in the household up until I was 12 (and then started smoking at 14, quit with 18)
So maybe thats part of it too
Its very interetsing all that, also scary
The good news of all this is that immune therapies are entering their golden age. Hopefully that means in the future you can be cured of these immune based diseases as we find the immune cell culprits like macrophages here.
In this case, the pathway affects macrophages, leucocyte activation and migration, and production of 3 inter-leukin's and other cytokines -- which doesn't offer much hope at avoiding off-target effects. As they mention, this gene is shared as far back as other proto-humans, so it's likely essential.
And they didn't really need this finding to consider targeting (toxic) MEK at macrophages using antibodies, particularly since GI drugs can be made relatively non-absorbable, further reducing off-target effects. But since these are chronic diseases with wide variations between patients of severity and tissue involvement, and since macrophage activity is relatively acute, the narrow therapeutic range of a MEK-based drug is far from ideal: too much opportunity for overdose.
So I hope this stimulates more investigation of the ETS2-mediated pathways, but I don't hold out much hope for a MEK + Ab drug for IBD.
> Lee’s research team “stumbled” on the discovery after investigating a “gene desert”, a stretch of DNA on chromosome 21 that does not code for proteins, which has previously been linked to IBD and other autoimmune diseases. Writing in Nature, they describe how they found a section of DNA that behaves like a volume control for nearby genes. This “enhancer” was seen only in immune cells called macrophages where it boosted a gene called ETS2 and ramped up the risk of IBD.
As parents we make plenty of real mistakes; blaming ourselves for unavoidable stuff isn't worth adding to the pile.
That appears to overwhelmingly not be the case, at least in the United States.
There's been a lot of really encouraging progress in the 15+ years since my diagnosis, but there are still a lot of unknowns. I got very little support in the dietary side of things other than the infamous elimination diet approach. It took a while for me to dial it in, but I did and am very rarely sick these days, now that I've discovered my own food sensitivities.
As much as you may want to solve this problem for him, it will take an immense amount of maturity on his part to want to discover and understand his limitations and to create and stick to a sustainable lifestyle.
No use whatsoever to blame oneself for something like this.
From a layman's point of view, IBD is a single disease. However, in reality, it's an umbrella term for a disease with a common set of symptoms and histological changes that can have a variety of underlying etiologies. Some people are more genetically susceptible, with family histories; others with no family history can undergo changes in gut microbiota composition, genome methylation, among other environmental factors that influence development and progression of the disease.
There are a bevy of peer-reviewed studies that show links between better diets/exercise and an increase in SCFA-producing microbiome components, which are known to suppress inflammatory cytokines and improve innate immune mucosal defense systems and free radical scavenging, promoting gut healing. On the flip side, plenty of people with poor diets and a lack of fiber are at a far higher risk of developing IBD or some other autoimmune disease (like SLE or RA), even certain cancers. It's why one of the most common strategies to address mild IBD and IBS cases is to begin an elimination diet and see which foods are triggers for inflammation.
You are correct that for many, diet isn't the reason why people have IBD. But it does play a huge role in symptom burden and the overall severity and prognosis of the condition. This isn't even considering the effect of environmental contaminants (such as PFOA and BPA) on IBD development, which has been well-known for over a decade now.
Ignoring science for a bit, just from the perspective of common sense, the idea of what you put in your body not affecting you is absurd and ridiculous. It's an idea pushed by gastroenterologists who don't want to risk upset patients who would rather not change their entire diet and lifestyle to mitigate their disease, for a small portion of whom the changes will not work anyways due to an underlying genetic component to the disease. Still, there's nothing to lose and everything to gain from adopting a healthier lifestyle.
IBS is a common set of symptoms. IBD is short for inflammatory bowel disease, and it's an umbrella term for Crohn's disease and ulcerative colitis (UC).
If this was the case, and IBD was a purely genetic illness with no environmental component, then it would be literally impossible to study it. In labs we force mice to ingest dextran sodium sulfate (DSS) which produces persistent colitis by degrading the gut mucosa. It's impossible to really tell without sequencing someone's entire genome whether their IBD comes from genetic factors or environmental factors.
Both IBD and IBS respond to changes in diet, as both diseases involve degradation of the gut mucosa. Obviously IBD is marked with inflammation as well, while IBS is marked only by dysbiosis and abdominal discomfort.
Happiness does not come from beating yourself up, but can come embracing and making the best of a situation.
Also watch for lactose intolerance, it's easily controlled but can cause discomfort when eating (I'm not saying your son has exclusively this, but rather in addition to).
"Crohn's disease is found in all racial groups worldwide. However, historically, the highest prevalence rates have been reported in white populations, particularly those of North America and Europe, with significantly lower rates seen in black and Asian populations within these or any other foreign country"
> Through gene editing experiments, the scientists showed that ETS2 is central to the inflammatory behaviour of macrophages and their ability to damage the bowel in IBD.
Sounds like a win for CRISPR-Cas9
> To directly confirm that ETS2 was causal, we used CRISPR–Cas9 to delete the 1.85 kb enhancer region in primary human monocytes before culturing these cells with inflammatory ligands, including TNF (a pro-inflammatory cytokine), prostaglandin E2 (a pro-inflammatory lipid) and Pam3CSK4 (a TLR1/2 agonist) (TPP model; Fig. 1d and Extended Data Fig. 2a–c). This model was designed to mimic chronic inflammation16, and better resembles disease macrophages than classical IFNγ-driven or IL-4-driven models17 (Extended Data Fig. 2).
i.e., gene editing (by whatever means) is not really a win any more than changing bits in memory is. The win comes from having an in-vitro model that replicates the in-vivo disease, or from correctly identifying the relevant genes (e.g., here ETS2 is the furthest gene considered, and could easily have been excluded).
I take your point, but this would have been a challenging, expensive endeavor before CRISPR-Cas9. Likely, the perturbation would not have been done in the same paper as the announcement of the locus due to the challenge of deletion work before CRISPR-Cas systems became readily available
This is after trying the Specific Carbohydrate Diet, 5-ASAs, adalimumab, ustekinumab, and vedolizumab, none of which offered more than minor relief.