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Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial

They say that they have used whole‐food blended smoothies but I do not see what ingredients in particular they have used on this study. Is there any way to figure this out?
 

kiny

Well-known member
Ok, so they have a supplemental file with info regarding their "smoothie".

This still doesn't say much though, I would like to know how they got to this profile. EN uses hydrolysis of starch to create glucose syrup for example, they're pretty specific methods. "Carbohydrates" doesn't tell me much.

"saturated fats" doesn't help much either. Both LCT and MCT can be saturated fats, but the structure of MCT and LCT is very different, and EN are very MCT biased.

Macronutrient Content of RE-EEN Smoothie
Supplemental Table 1: Macronutrient Content of RE-EEN Smoothie

Nutrients Per Serving*
Gram Weight (g) 1152.5
Calories (kcal) 1078.78
Calories from Fat (kcal) 433.37
Calories from SatFat (kcal) 75.26
Protein (g) 48.08
Carbohydrates (g) 126.44
Total Dietary Fiber (g) 13.72
Total Sugars (g) 85.91
Added Sugar (g) 36.95
Monosaccharides (g) 24.82
Disaccharides (g) 15.02
Other Carbs (g) 25.56
Fat (g) 48.6
Saturated Fat (g) 8.36
Mono Fat (g) 29.35
Poly Fat (g) 8.2
Cholesterol (mg) 25.2
Water (g) 921.63
 
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kiny

Well-known member
So you can try to deduct what they used a little bit. 48g of total fats. of which 8.36g are saturated. So that's 17% saturated. Since MCT are (largely) saturated, the smoothie can't contain much MCT. Likely much less than in EN.

There's this whole scientific debate if the MCT in EN purely help with absorption, or if they actually lower inflammation. Would be interesting to see the MCT profiles of the smoothie. It seems low, since saturated fats are low, but I can't be sure.

They added the amount of water, so we can find the liquid-to-solid ratio for the smoothie, which is 3.99 . This is exactly like Modulen.
 
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kiny

Well-known member
Great, thank you. Hopefully we see more of these type of studies.

For comparison, here is the change in FC during a regular course of EEN in the 2024, UK study:

"Treatment of Active Crohn's Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products"


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kiny

Well-known member
For what it's worth, I remembered there was an older thread where forum users mentioned using smoothies.

From 2011: https://crohnsforum.com/threads/smoothies.27556/

Anyway, hopefully more studies are done. Compliance is the biggest issue holding back more widespread use of EN. Although EN like Modulen already tastes much better than the Vivonex stuff they used to use in studies.
 
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very nice! As far as I recall the usual term for EEN was 8 weeks, this study kept them on for 4 weeks. While they measured fecal calprotectin, we may not fully know how it measures up to typical EEN until endoscopic remission was measured. Another good thing is there are no additives in this smoothie, and it contains fiber, which also might be better then manufactured EEN formulas. This could be an improvement or another future option for people!

Another thought, since EEN usually has little to no fiber, the presence of fiber really could be an advancement, but the type of fiber is crucial, as there is some evidence inulin is shown to be abnormally fermented in crohns microbiota. The information we have now on how detrimental low fiber diets can be on the microbiome, might eventually call for a reevaluation of manufactured EEN formulas that have no fiber. I recall a study that showed lowered diversity in important microbes after EEN. So it might put people in remission but create long term damage, worsening the disease state, since the prime cause of crohns is suspected to be lower microbiome diversity which Fecal Microbiota Transplants aim to correct.

And again, this study on reverse engineered EEN, reported a reduction in blautia which are buytrate producers and most likely anti-inflammatory. IBD is typically lower in butyrate producing microorganisms. I would think this RE-EEN formula would not have that effect, so I wonder why this happened?
 
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kiny

Well-known member
the prime cause of crohns is suspected to be lower microbiome diversity which Fecal Microbiota Transplants aim to correct.
Fecal transplants are an unregulated treatment that caused major flares in crohn's disease patients in multiple studies.

The fecal stream is a major contributor to inflammation in crohn's disease:
(1) Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum.
(2) Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum.
(3) Role of the faecal stream in the maintenance of Crohn's colitis.

Fecal transplants are no longer performed on crohn's disease patients in the West, lest doctors want to open themselves up to lawsuits.


"Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile

Department of Medicine, University of California San Francisco

''We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT.

The study was halted prematurely because of a presumed CD flare in two patients within a few days of undergoing FMT.

The first patient was a 37-year-old woman with colonic CD who had been diagnosed 10 years prior to enrollment in this trial. Her previous therapies included mesalamine and steroids. She was not on any therapy at the time of FMT. Within a few days of the procedure, she developed worsening abdominal pain and diarrhea. Her fecal calprotectin increased from 475 to >2000 µg/g. CRP increased from 2 to 15.5 mg/l and HBI increased from 3 to 16.

The second patient was a 32-year-old woman with colonic CD. She had been diagnosed 16 years prior to enrollment in the study. She had previously failed adalimumab and infliximab (responded initially with subsequent loss of response) and was on certolizumab at the time of FMT. She had required courses of steroids on several occasions but none in the last year prior to FMT. The day following FMT, this patient experienced increased abdominal pain and diarrhea severe enough to require inpatient admission for intravenous hydration and steroids. Her HBI increased from 11 to 13 post-FMT. CRP increased from 18.3 to 33.1 mg/l.

In this prospective, open-label study of FMT in CD, 30% of patients achieved the primary outcome of improvement of HBI ≥3 points one month post-FMT; however, there was no significant improvement in objective measures of inflammation such as fecal calprotectin and SES CD score.

Two patients in this cohort experienced adverse events requiring escalation of therapy within a few days of FMT that prompted early termination of the study.

Conclusions
Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm''
 
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@kiny, what are you thoughts on this?
I'm thinking of asking my doctor and trying this out. My crohns was first discovered with a cdiff infection. Not sure if that matters, but I feel like it might be related.
 
Fecal transplants are an unregulated treatment that caused major flares in crohn's disease patients in multiple studies.

The fecal stream is a major contributor to inflammation in crohn's disease:
(1) Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum.
(2) Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum.
(3) Role of the faecal stream in the maintenance of Crohn's colitis.

Fecal transplants are no longer performed on crohn's disease patients in the West, lest doctors want to open themselves up to lawsuits.


"Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile

Department of Medicine, University of California San Francisco

''We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT.

The study was halted prematurely because of a presumed CD flare in two patients within a few days of undergoing FMT.

The first patient was a 37-year-old woman with colonic CD who had been diagnosed 10 years prior to enrollment in this trial. Her previous therapies included mesalamine and steroids. She was not on any therapy at the time of FMT. Within a few days of the procedure, she developed worsening abdominal pain and diarrhea. Her fecal calprotectin increased from 475 to >2000 µg/g. CRP increased from 2 to 15.5 mg/l and HBI increased from 3 to 16.

The second patient was a 32-year-old woman with colonic CD. She had been diagnosed 16 years prior to enrollment in the study. She had previously failed adalimumab and infliximab (responded initially with subsequent loss of response) and was on certolizumab at the time of FMT. She had required courses of steroids on several occasions but none in the last year prior to FMT. The day following FMT, this patient experienced increased abdominal pain and diarrhea severe enough to require inpatient admission for intravenous hydration and steroids. Her HBI increased from 11 to 13 post-FMT. CRP increased from 18.3 to 33.1 mg/l.

In this prospective, open-label study of FMT in CD, 30% of patients achieved the primary outcome of improvement of HBI ≥3 points one month post-FMT; however, there was no significant improvement in objective measures of inflammation such as fecal calprotectin and SES CD score.

Two patients in this cohort experienced adverse events requiring escalation of therapy within a few days of FMT that prompted early termination of the study.

Conclusions
Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm''
I'm aware of the variety of reports on FMT, both the successes and the failures.

Here's one thing to consider about the info you posted, this was a colonoscopic FMT and IBD flares can happen due to just colonoscopy alone, so it is not so clear that even the FMT caused the flare in these examples.

Although depending on how FMT is performed and prepared, it is possible for FMT to cause harm, but you have to almost know nothing about how its done, for it to do harm. Besides FMT is already FDA approved to treat antibiotic refractory C diff infection, which is almost a death sentence. From what we know, FMT is doing more good then harm at this point.

 
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