Intestinal fungal commensals and food-derived yeasts, drives inflammatory CD4+ T cell responses in patients with CD

[kiny]

Nature Medicine
University Medical Center Schleswig-Holstein, Kiel, Germany
Cornell University, NY, USA
25 of september 2023

 

[kiny]

 

[kiny]

For what it's worth. Most of the weird immune terms being used and the implication of diet mentioned in the study.

T helper cells, or CD4+ T cells, and their subgroups, Th1, Th2, and recently the newly discovered third subset and was named Th17. The cytokine Th17 releases is interleukin 17. Note that IL-17 blockade failed in crohn's disease trials. When CD4+ T cells notice microbes in the intestine, these 3 subgroups, Th1, Th2 and Th17 proliferate.

Another term is interferon Y, or IFN-Y, or interferon gamma, all the same thing. It's easy to remember, the reason it's called interferon...is because it interferes with viral infection. IFN-Y is a macrophage activator. These macrophages, which the intestine has extremely high concentration of, cause phagocytosis of microbes. Your innate immune response to fungi and bacteria is the physical mucus layer, the epithelial cells, anti-microbial peptides, and activation of macrophages and dendritic cells in the tissue below, or lamina propria.

Anyway, this ASCA test that is often used to differentiate CD from UC, tests for antibodies against the carbohydrate cell wall of S. cerevisiae. About 60 percent of people with CD are ASCA+, meaning they react to baker's yeast, or there is some cross reactivity going on. The relevance of this has been questioned a lot, because healthy people consume bread and other nutrients with this yeast all the time without issues, but this is a solid study showing people with CD with ASCA+, react to this yeast. If you are ASCA+, and your medical records should be able to show this, it is probably advised to limit these fibers to limit the exposure of immune cells to S. cerevisiae.

 

[kiny]

If they're correct and the fungi are coming from oral sources, then it's important to wrinse your mouth with water after you drank EN. Not because there's fungi in EN, there's obviously not, but becausing just leaving EN in the mouth is just a sure way to fuel candida, you also don't want EN to touch your teeth. Avoiding dietary yeast is not difficult, it's found in products using leavening agents like batter, pastry and bread, and it's in a handful of dairy products.

 

[kiny]

Interesting to note is that biopsy tissue T4 cells from CD patients reacted to Saccharomyces boulardii, often used in probiotics. Probiotics have shown no benefit in crohn's disease, and could very well invoke strong immune response.

 

[westernbuddy]

What would be your latest update Kiny? as regards to research and breakthroughs and new medications as a summary.

How is the crohns world progressing do you think?

We do have new meds there has been more research, are you noting anything that is pointing in any direction more clearly with the science, and any new meds to support this?

I guess also that not all known info is available for everyone yet from labs or pharma companies either.

 

[kiny]

We're not very good dealing with stenosis and fistula. Crohn's disease is a penetrating disease for many. A lot of young kids with crohn's disease tend to now have an aggressive disease course, including penetrating disease, meaning they develop lots of fistulas early on. No organ is more capable of renewing itself than the intestine. But deregulated wound healing results in stenosis or fistula. A lot of researchers are looking at how this process actually occurs in the intetine and how fibroblasts are activated and which growth factors are involved in it. Closing internal fistula and reversing stenosis is a goal for much of the research. It should be possible to stimulate closure of fistula for examply by activating fibroblasts.

 

[kiny]

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[kiny]

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[kiny]

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[kiny]

Immunologic responses to food antigens is a potential explanation for V. Kruiningen's clustering studies, the therapeutic effect of EN as an exclusion diet for crohn's diseae, and the failure of EN in UC lacking in immune response to yeasts.

 

[kiny]

Common onset of crohn's disease is puberty. Explanation for this is uknown.

An exlanation I proposed is the activity of Peyer's patches during puberty, common foodborne pathogens like salmonella and close-kin E coli tend to gain entry through m cells.

But a reasonable explanation would also be changes in food patterns around puberty.

 

[Kblee206]

Common onset of crohn's disease is puberty. Explanation for this is uknown.

An exlanation I proposed is the activity of Peyer's patches during puberty, common foodborne pathogens like salmonella and close-kin E coli tend to gain entry through m cells.

But a reasonable explanation would also be changes in food patterns around puberty.

my 21yo son was recently diagnosd with crohn's with moderate inflammation in the terminal ileum and rectum. - he has had lifelong allergies to tree nuts (except almonds) and peanuts and cow's milk, although he was able to eat dairy cooked in cakes etc. He had been taking in small amounts of biosimilar milks like camel and mares milk through an allergy program we enrolled him in to build tolerance to his allergens. he started the allergy treatment in july, noticed bleeding in september and got diagnosed end of december. He is without much other symptoms, no weight loss or pain - it was just the bleeding..... i have wondered if it was the allergy program and introduction of the milks that have triggered this---- any thoughts? They want him to start a biologic of course.... i am wary

 

[asadmom]

Immunologic responses to food antigens is a potential explanation for V. Kruiningen's clustering studies, the therapeutic effect of EN as an exclusion diet for crohn's diseae, and the failure of EN in UC lacking in immune response to yeasts.

Kiny, what do you mean by " the failure of EN in UC lacking in immune response to yeasts"?

 

[kiny]

They want him to start a biologic of course.... i am wary

Discuss your worries with the GI. Anti-TNF and EN are both very effective in inducing remission and reversing fistula in ileal crohn's disease, and can be used in combination.

Combination of anti-TNF and EN can prevent loss of response https://link.springer.com/article/10.1007/s10620-014-3493-8 and avoid dose escalation.

Other medication is not as effective (Stelara), has very questional effectiveness (Entyvio) or has considerable side-effects when used long-term (steroids).

 

[kiny]

Kiny, what do you mean by " the failure of EN in UC lacking in immune response to yeasts"?

ASCA testing tests for antibodies against a carbohydrate cell wall of S. cerevisiae, it binds what is commonly known as baker's yeast. But it also binds to other yeasts like candida.

ASCA is very specific to crohn's disease. About 60% with crohn's disease are ASCA+. In UC it is around 5%-10%, in healthy controls it is 0%-5%. So it's a very good marker for crohn's disease.

The ASCA seropositivity in crohn's disease is very unlikely to be just due to increased permeability, since we don't see this for other types.

Interestingly, there is another group of patients with ASCA+, and that's patients with celiac disease. In fact celiac disease is common among people with crohn's disease.

There's always been speculation that there is some kind of connection between Crohn's disease and Celiac disease. Because of the prevalence of celiac disease among CD patients, and because of the ASCA testing, and now because we see that strong CD4 T cell response seemingly driven by yeasts (the Nature study in the thread).

So I said :

"the failure of EN in UC lacking in immune response to yeasts"

The failure of EN to induce sustained remission in UC compared to its well proven track record in crohn's disease, might be related to the exclusion of yeasts and EN might be mitigating yeast in the intestine.

It would be interesting to see if the people who respond best to EN, are ASCA+.

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[kiny]

These aren't crohn's patients, but it's very interesting to see MCT reduce gastrointestinal candida growth. Considering most EN uses MCT to increase absorption. It isn't explained in the study, but MCT are able to suppress biofilm formation of candida and limit hyphal growth.

There's a debate about the MCT in EN, is it an active component reducing inflammation in crohn's disease, or does it not matter.

Dietary Supplementation With Medium-Chain Triglycerides Reduces Candida Gastrointestinal Colonization in Preterm Infants

Department of Pediatrics, Women & Infants Hospital of Rhode Island.

Background:
Candida is an important cause of infections in premature infants. Gastrointestinal colonization with Candida is a common site of entry for disseminated disease. The objective of this study was to determine whether a dietary supplement of medium-chain triglycerides (MCTs) reduces Candida colonization in preterm infants.

Methods:
Preterm infants with Candida colonization (n = 12) receiving enteral feedings of either infant formula (n = 5) or breast milk (n = 7) were randomized to MCT supplementation (n = 8) or no supplementation (n = 4). Daily stool samples were collected to determine fungal burden during a 3-week study period. Infants in the MCT group received supplementation during 1 week of the study period. The primary outcome was fungal burden during the supplementation period as compared with the periods before and after supplementation.

Results:
Supplementation of MCT led to a marked increase in MCT intake relative to unsupplemented breast milk or formula as measured by capric acid content. In the treatment group, there was a significant reduction in fungal burden during the supplementation period as compared with the period before supplementation (rate ratio, 0.15; P = 0.02), with a significant increase after supplementation was stopped (rate ratio, 61; P < 0.001). Fungal burden in the control group did not show similar changes.

Conclusions:
Dietary supplementation with MCT may be an effective method to reduce Candida colonization in preterm infants.

 

[kiny]

There's a debate about the MCT in EN, is it an active component reducing inflammation in crohn's disease, or does it not matter.

Effect of fat composition in enteral nutrition for Crohn's disease in adults: A systematic review

Background & aims: The role of enteral nutrition (EN) fat composition in regulating inflammation in Crohn's disease (CD) is not clear. There is, moreover, insufficient evidence to guide the choice of EN in CD with any confidence. We have reanalysed the findings of previous studies in a systematic review focussing on the relationship between EN fat content and remission rates (RR).

Methods: A systematic search with no language restriction was undertaken in Medline and Embase databases supplemented by a manual search in the reference lists of identified studies. The selection criteria were: clinical trial, exclusive EN, adults and CD. Data on the type of EN, its fat composition, achieved RR, and study design were extracted. An established assessment tool was used to assess the quality of the studies.

Results: A total of 29 clinical trials are included in this review. The quality of the studies was highly variable. No fewer than 27 formulations of enteral feed were identified including 4 elemental and 23 non-elemental preparations. There was a positive correlation between the total n-6 fatty acid content and response rates, which was significant when expressed as the ratio between n-6 and n-3 fatty acids (r = 0.378, p = 0.018). A non-significant positive trend was founded (r = 0.072; p = 0.643) between medium chain triglycerides (MCT) delivery as a percentage of the total energy provision and RR. While a non-significant negative trend was reported for the delivery of monounsaturated fatty acids (MUFA) (r = -0.23, p = 0.13). A qualitative advantage to regimens based on safflower oil suggest that optimised therapeutic approaches are within reach.



Long-chain triglycerides reduce the efficacy of enteral feeds in patients with active Crohn's disease

Elemental diets are effective treatments for active Crohn's disease. To determine which dietary constituents are of therapeutic importance, the effectiveness of four separate feeds was related to their compositions, and the findings substantiated by meta-analysis of previous dietary studies. 76 patients with active Crohn's disease were recruited. 17 were randomised to an amino acid-based elemental diet (E028), 22 to E028 with added long-chain triglyceride (E028 LCT), 18 to a semi-elemental, peptide based diet (Pepdite 2+) and 19 received E028 with added medium-chain triglyceride (E028 MCT). Disease activity fell in all groups and remission rate was negatively correlated with the amount of energy derived from LCT (r = -0.97, p = 0.016). Inflammatory indices fell in the groups (E028 + E028 MCT) containing least LCT. No other dietary constituents correlated with remission rate. A meta-analysis of published studies confirmed a negative correlation between remission rate and LCT (r = -0.63, p = 0.006) but not other constituents. The association between dietary LCT and remission rate may have pathogenic significance and allow the development of more effective enteral feeds.

 

[kiny]

Dietary Supplementation With Medium-Chain Triglycerides Reduces Candida Gastrointestinal Colonization in Preterm Infants

Interestingly, in a follow up study, they determined that even though MCT drastically lowered fungal load, 3 weeks of MCT supplementation had no effect on the bacterial microbiome (dominated by Enterobacteriaceae in infants).

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[asadmom]

I just saw a bunch of posts on reddit of using MCT oil to "cleanse" candida. I was expecting herbal options so this is all very enlightening.

 

[kiny]

Logal et al analysed 61 EN formulas, including those specifically used for crohn's disease.

Fat sources were mainly derived from Sunflower oil, Canola oil, Soybean oil and Coconut oil.

Only 3% of EN formulas (2/58) were free of fat.

49% of those who content reported, contained MCT.

The popular EN specifically used for Crohn's disease and discussed on this forum, contain high amounts of fat, higher than standard EN formulas. They often completely lack any fiber, those that do contain fiber, have amounts much lower than those measured in Nutrition surveys.

 

[kiny]

Note the high prevalence of additives in EN, which I've pointed out many times. Many theorized those to be harmful for crohn's disease patients, like emulsifiers, polypolysorbate 80 and matodextrin.

In reality, they have absolutely no effect on remission rates.