Mechanisms of Action of Exclusive Enteral Nutrition and Other Nutritional Therapies in Crohn’s Disease

[kiny]

https://www.mdpi.com/2072-6643/16/21/3581



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Figure 1. Proposed mechanisms of action of EEN in Crohn’s disease (CD). Transmural inflammation and stenosis in CD lead to increased mechanical stress (MS) in the inflamed tissue and the segment proximal to inflammation. Both the inflammatory process and MS may induce proinflammatory molecules (i.e., COX-2), cytokines and chemokines (i.e., IL-6, IL-8, osteopontin), and pain mediators (i.e., prostaglandin E2, nerve growth factor). CD is also associated with microbiota dysbiosis in the lumen. The altered gene expression and dysbiosis are responsible for inflammation, immune responses, barrier dysfunction, fibrosis, visceral pain, and dysmotility in CD. EEN treatment with liquid diet is found to reduce inflammation and immune responses, improve barrier function and motility, and restore microbiota composition and diversity. Recent studies found that these benefits may be due to EEN’s effect to attenuate MS and MS-dependent pro-inflammatory gene expression. Notes: EEN, exclusive enteral nutrition; CD, Crohn’s disease.

 

[kiny]

The mechanism of action of EN simply being related to its liquid form, resulting in a reduction of mechanical stress on the bowel wall, would make this treatment regime much more palatable, cheaper and easier to implement.

 

[kiny]

Anthony Segal suggested early lesions from an acute infection, like a common foodborne infection, would leave the intestine exposed to fecal content entering intissue tissue.

Rutgeerts pointed out that the fecal stream drives inflammation, and removal of this fecal stream or filtered with an ultrafiltrate, leads to healing. Direct contact between fecal effluent and tissue resulted in inflammation.

Reducing luminal mechanical stress from the fecal stream, should reduce contact between the fecal stream and the bowel wall. If all it takes is employing a liquid feed, then simple turning your diet into a liquid diet should help.

(Anthony Segal)

 

[kiny]

Most bacteria don't come near the bacterial wall, PP, or TLR, they seem to keep their distance and we have adapted to have a certain immunological tolerance towards them when they accidentally do. What differentiates pathogens is their ability to invade tissue, including adherence, pathogens will literally attach themselves to enterocytes in the intestine. I assume mechanical stress from the fecal stream can drive these pathogens into tissue. When Rutgeers used an ultrafiltrate, these bacteria would have been filtered out.

 

[Veske]

Have you actually tried this your self? As in... turning all your food into a blended mush.
This lady here seems to be doing just fine with such way of eating:

 

[Soryan]

If this is the case, it would be interesting to see the effect of (a) fasting, (b) non-EN fluid / liquid diet (e.g. bone broth/juice), compare to EEN.

Also PEN doesn’t work that well as EEN, guess the fecal stream has to be reduced to a level such that it contacts minimally with our bowel wall?

 

[my little penguin]

Not sure on non en liquid
But fasting (Tpn ) has been studied
While it rests the gut it is not as effective as een from what I remember.
They only use tpn prior to surgery for that reason

 

[kiny]

You would need 4 weeks of treatment to make these comparisons, the point at which calprotectin shows a drastic change in EN patients.

TPN studies are really hard to find. They are often malnourished children or people with a non-functioning bowel. I was on TPN due to severe anorexia, I have a fully functioning bowel and have crohn's disease. But even for patients like me, we were put on it for 1 week, any longer increases the risk of sepsis. It is not used to gain weight, in severe anorexia cases it is to prevent kidney issues, prevent bone loss, etc. After that you are put on EN or a regular diet.

It makes no sense just to put people on TPN to treat crohn's disease, EN works and doesn't have the risk of sepsis. TPN is useful in very severe cases of anorexia or malnutrition, but that is not for 4 weeks usually.

 

[kiny]

I can only assume fasting is dangerous and not helpful for crohn's disease, and why I always react sceptical when people suggest it. The enterocytes I mentioned line the small intestine, they have a very fast turnover to repair themselves, they need a lot of nutrients to do this, glutamine especially but many others too. It's those enterocytes that are your first protection against bacteria, they serve as a physical barrier, they recognize bacteria through TLR, they produce defensins. The last thing you probably want to do is to undermine their quick turnover, they need nutrients to build up that barrier again after inflammation.

 

[jadegreen]

Have you actually tried this your self? As in... turning all your food into a blended mush.
This lady here seems to be doing just fine with such way of eating:

I eat a blended smoothie every morning for breakfast. It's pretty near liquid I found a recipe I like from a guy with UC on YouTube. I could find it back, if interested.

I also eat a lot of soups. Sometimes I puree them, but always have well-cooked veggies. When I had a flare up this past Feb or March, I did bone broth only for 3 days and slowly added SCD-permitted foods and recovered after a couple of weeks. My calprotectin levels were all normal when I got tested about 3 or 4 months later.

I'm trying to get imaging scheduled for this Jan or Feb so I can let you know what that shows, if anyone's interested.

Thanks for sharing this paper, I hope I can look at it more closely after Christmas.

 

[jadegreen]

Also, I heard a rumor that Seattle Children's Hospital is trying to do a study where they blend SCD-approved foods into smothie form to see if it can induce and/or maintain remission.

 

[jadegreen]

https://www.seattlechildrens.org/clinics/gastroenterology-hepatology/research-and-clinical-trials/

 

[Andersen007]

If this is the case, it would be interesting to see the effect of (a) fasting, (b) non-EN fluid / liquid diet (e.g. bone broth/juice), compare to EEN.

With mild ileal Crohn’s disease, EEN has never worked for me unfortunately. Compliance was not an issue as I really liked it, but most formulas gave me horrible diarrhea and episcleritis as well as increasing calpro. The most I could do was 2.5 weeks tho - I felt its too risky to continue.

I tried fasting and broths too and I dont think they helped either.

What worked realy well for me is Compleat Chicken Garden Blend. I was on it 3 weeks while in the US and by the 3rd week I could even add 10-20% real foods - foods that otherwise I never tolerated - and coffee.

Since then I do 80% of my food via homemade EEN but worth noting its not liquid, more like a pudding / purey. I have never felt so good nor could I afford to eat foods before that I can now in the 20%. I also had an MRE that shows no active signs of disease.

But then again I am not even sure I have Crohns in the standard sense. Sure I have something that causes gut inflammation but I have my calpro move from 400 to 2000 then back to 300 within 2-3 weeks. The worst thing they saw on biopsies were 2 minor apthous ulcers and minor inflammation and mild wall thickening even when my calpro was really really high. I was consistently negative on CRP, negative for granulomas, negative for ASCA. This, combined with how quickly I move in and out of a “flare”, my flares being the absolute worst on EEN, the lack of any medication needed for 2 years, and my very mild symptoms (I feel much better with Crohns on a diet than I did in the 10 years before with IBS), made even my IBD specialist contemplate what this really might be. In my head its more like some sort of hypersensitivity, where consistency can trigger stuff just as much as the food itself.

 

[aga]

You may be right.
Do you have an idea what can cause that hiperintensivity?

 

[padrach3]

The mechanical stress theory seems plausible but doesn't explained why surgical diversion doesn't seem to put most patient into remission.

 

[Andersen007]

The mechanical stress theory seems plausible but doesn't explained why surgical diversion doesn't seem to put most patient into remission.

Doesn’t it? I read that TPN as well as surgical diversion such as ileostomy have pretty great success rates and inflammation tends to recur when flow of food continues

 

[kiny]

The mechanical stress theory seems plausible but doesn't explained why surgical diversion doesn't seem to put most patient into remission.

It does, the fecal stream drives the inflammation and recurrence of inflammation. This is well established.

Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum​

https://www.thelancet.com/journals/lancet/article/PII0140-6736(91)90663-A/fulltext

Our findings strongly support the view that recurrence of Crohn's disease in the neoterminal ileum after curative ileal resection is dependent on faecal stream.

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Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum.​

https://researchinformation.amsterd...urrent-crohns-disease-caused-by-infusion-of-i

Intestinal contents trigger postoperative recurrence of Crohn's disease in the terminal ileum proximal to the ileocolonic anastomosis in the first days after surgery.

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Role of the faecal stream in the maintenance of Crohn's colitis.

https://gut.bmj.com/content/26/3/279.long

In conclusion, these results suggest that factors greater than 0.22 microns in the faecal stream are responsible for the maintenance and exacerbation of inflammation in Crohn's disease.

 

[kiny]

The question isn't if the fecal stream drives inflammation, it does, the question is why.

Filtered with an 0.22 micron ultrafiltrate, fecal effluent no longer results in inflammation. A 0.22 micron filter takes out bacteria, fungi and many, but not all, dietary particles.

 

[kiny]

Also, I heard a rumor that Seattle Children's Hospital is trying to do a study where they blend SCD-approved foods into smothie form to see if it can induce and/or maintain remission.

That's very cool. Even though there's few studies yet, "smoothies" that mimic EN seem to work:

https://onlinelibrary.wiley.com/doi/10.1002/jpn3.12196
"A whole-food blended smoothie was able to induce clinical and biochemical remission of active Crohn's disease."

61 different liquid formulas that result in remission have been noted by Logan et al., 2020. Many contained emulsifiers, thickeneres, stabilizers (including some carageenan). They are all effective.
https://www.researchgate.net/publication/340462386_Analysis_of_61_exclusive_enteral_nutrition_formulas_used_in_the_management_of_active_Crohn's_disease-new_insights_into_dietary_disease_triggers

The dietary room you have to play with in terms of these liquid formulas seems very wide, which should help palpability for people who are apprehensive about the taste.

 

[kiny]

I can only assume regular infant formulas are effective too, even though they might not have the perfect nutritional profile for adults.

Nestlé created this whole infant formula industry over a century ago, and crohn's disease studies have used many of their products.

Segal used Nestlé's Vivonex to show you could induce remission in crohn's patients with it, as did many others using vivonex. Modulen did not exist yet.