What is inside the fecal stream that is driving inflammation.

[kiny]

The fecal stream is behind the inflammation in crohn's disease. Rutgeerts et al. showed contact with intestinal fluids in patients caused disease within 8 days.(1) (2)

Harper confirmed this a third time (3). Small bowel effluent causes inflammation.

However, patients that received an enema of effluent that first went through a 22-nm ultrafiltrate showed no such response. Showing that fecal content larger than 0.22 micron is responsible for the inflammation. Either bacteria or large particles in the fecal stream cause the inflammation. (3)

Macrophages within the lamina propria show an immune response to E. coli, Streptococci and Listeria (4).

Serological markers like anti-OmpC can predict CD disease years before the diagnosis. (5)


(1) ''Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. https://www.ncbi.nlm.nih.gov/pubmed/9453485 ''

(2) ''Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum
https://www.ncbi.nlm.nih.gov/pubmed/1681159''

(3) ''Role of the faecal stream in the maintenance of Crohn's colitis
https://gut.bmj.com/content/gutjnl/26/3/279.full.pdf ''

(4) ''Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus antigens in Crohn's disease.
https://www.gastrojournal.org/article/0016-5085(95)90687-8/pdf''

(5)''Serological markers predict inflammatory bowel disease years before the diagnosis.
https://www.ncbi.nlm.nih.gov/pubmed/22842615''

 

[D Bergy]

I would think it is the fecal stream that feeds the existing bacteria responsible for the inflammation. In some instances I also would speculate that some foods have components that are similar to some secretions output by certain bacterium which increase inflammation. That is the hypothesis I came to regarding my adverse reaction to onions when I was ill. I can eat them without any consequences now.

It would be difficult to explain long term remission otherwise. Especially when not using a typical Crohn’s treatment.

Much of our food is both GMO and doused In glyphosate which adds another layer of complexity to it all.

Dan

 

[Mommabear]

Interesting but these studies are old. Have none of these avenues been followed since these findings were published? I had understood that there were as yet no identified antigens in Crohn’s, hence the constant speculation of different causes. And if the bug(s) is larger than 22n-m then why hasn’t it or they been identified since these publications? Frustrating! It seems like we just go around and around!

 

[D Bergy]

I think the speculation about different causes is because there are different causes and often multiple causes. Thats why its a difficult thing to get under control.

Based strictly off of my own alternative treatment results, mycoplasma pneumonia and H-Pylori were larger factors concerning inflammation than MAP and E-Coli although all were involved. The H-Pylori must have been right in the gut lining as killing it (too quickly apparently) caused a fire like burning in the gut that I have never experienced before. Once that healed though, things improved considerably.

I could be wrong, but I doubt it.

Just an opinion.

Dan

 

[TraceyA]

What do you think about the idea of low stomach acid being part of the puzzle?

Stomach acid is needed to assist the digestion of meat to extract iron and other nutrients. Its other role is to sterilise or destroy unwanted bacteria. If stomach acid is insufficient then these functions will not work properly.

Presumably loads of stomach acid is not needed to digest and sterilise EEN (which comes sterile and predigested) which could explain why EEN works.

Given that food digestion is such a main part of the digestive tract I find it quite incredible that gastroenterologists have so little concern about the saliva, acid, bile, enzymes and mechanics of a Crohn's patient and also pay little attention to the food which is being consumed. Surely both these parts have an integral role to play in the disease?

I also wonder about the role of baker's yeast. Why are so many Crohnies found to be ASCA positive? Why would anyone need/develop antibodies to yeast if it was not a problem in some way? Maybe sufficient stomach acid is needed to neutralize yeast? Removing yeast from the diet is not an easy task- it is in so many foods, not just bread.

The other thing EEN is free of is gluten. Gluten has been shown to play a big part in gut problems. It just might be that stomach acid or some other enzyme can neutralise gluten so that it is harmless.

Some crohnies have claimed that apple cider vinegar has helped them so maybe it is the PH factor doing the job.

 

[kiny]

Why are so many Crohnies found to be ASCA positive?

Why would anyone need/develop antibodies to yeast if it was not a problem in some way?

Right, you can detect anti-fungal IgG in the blood of crohn's disease patients. Malassezia and Candida albicans are associated with crohn's disease.

Patients with primary immunodeficiencies, often develop severe fungal infections.

Anti-OmpC implicates E. Coli.

 

[wild_one353]

couldn't any micro-organism from the external world cause inflammation? because that would be in the fecal stream.

 

[TraceyA]

Yes Wildbill, micro-organisms can and do cause problems, inflammation being one of them, but not always. Most of the time the digestive process of saliva, acid and bile destroys the baddies while the good ones are allowed in. However, sometimes a bad one gets through the chemical bath and that's when the immune system comes into play.

A good immune system will be effective without needing to resort to inflammation so the person isn't even aware of a the bug, but it depends on the bug. Something like listeria usually makes people feel very unwell but eventually the immune system eliminates it through a combination of inflammation, flushing and fever.

The problem with CD and allergies is that the immune system does not work correctly. It attacks the wrong things or fails to attack at all.

 

[kiny]

couldn't any micro-organism from the external world cause inflammation? because that would be in the fecal stream.

In a patient with active inflammation, it's intestinal bacteria or fungi present in the fecal matter that is causing inflammation. They're lumen bacteria sticking to the intestinal wall that the fecal stream physically moves around.

Most people think of the intestinal mucosal tissue as static. In reality it is very mobile and moves around all the time, it does this to mitigate migration of bacteria into the lamina propria. But even an intestine with complete mucosal healing remains incredibly permeable. Bacteria and fungi can enter through peyer's patches for example.


Regarding the ''external bacteria'' question. The bacterial load of a normal diet is quite high, especially plant based diets can be very high in bacterial load. A simple piece of fruit contains thousands of bacteria. Dieticians might argue these are ''healthy'' bacteria, but what is considered healthy for a normal individual might cause inflammation in crohn's disease patients.

EN probably works by limiting the fecal stream, and its bioavailability depletes intestinal bacteria from the necessary nutrients to survive. Intestinal bacterial load decreases on EN. I think this is less important...but what EN also does is simply decrease the amount of bacteria you ingest.

 

[kiny]

Regarding the ''external bacteria'' question. Due to the prevalence of salmonella and campylobacter infections in the West...it is inevitable that some people with crohn's disease will at some point be (re)infected with salmonella or campylobacter. Someone with active disease and active lesions, would flare without a doubt if they come into contact with salmonella or campylobacter.

Foodborne infections of course don't explain persistent inflammation, the persistent inflammation is being caused by something perpetually present in the fecal stream, but the foodborne infection would cause lesions that allow fecal matter to come into contact with the intestine without the mucosal layer acting as a barrier.

 

[Precious Time]

Question about the bacteria and fungal theory: Long story short. I am diagnosed with indeterminate colitis, My colon was disconnected at the ileum 1 1/2 years ago and I am still inflamed. Would the bacteria and fungus still cause inflammation in the large intestine? If fecal matter is a theory in causing inflammation, what about a person that does not have fecal matter? I only have mucus, dead cells and blood discharge from large intestine. Could it be that the bacteria are feeding on things brought to the colon by the blood stream?

 

[westernbuddy]

If it truly works.

It will get us all out of a sticky situation.

 

[asadmom]

 

[kiny]

In vitro mucin degradation and paracellular permeability by fecal water from Crohn's disease patients

2024 Mar 12
ahead of print

Department of Gastroenterology/Hepatology, Maastricht University, The Netherlands

Aim: This study aimed to examine the impact of fecal water (FW) of active and remissive Crohn's disease (CD) patients on mucin degradation and epithelial barrier function.
Methods: FW and bacterial membrane vesicles (MVs) were isolated from fresh fecal samples of six healthy controls (HCs) and 12 CD patients. Bacterial composition was determined by 16S rRNA gene amplicon sequencing.
Results: In vitro FW-induced mucin degradation was higher in CD samples versus HC (p < 0.01), but not associated with specific bacterial genera. FW of three remissive samples decreased transepithelial electrical resistance in Caco-2 cells by 78-87% (p < 0.001). MVs did not induce barrier alterations.
Conclusion: The higher mucin-degradation capacity of CD-derived FW might suggest contributions of microbial products to CD pathophysiology.

 

[kiny]

FW-induced mucin degradation was higher in CD samples versus HC (p < 0.01), but not associated with specific bacterial genera.

The CD fecal stream high in bacterial products is associated with mucin-degradation, but there is no association with relative abundance of bacteria after sequencing tests.

 

[kiny]

In a patient with active inflammation, it's intestinal bacteria or fungi present in the fecal matter that is causing inflammation. Fecal content larger than 0.22 micron is responsible for the inflammation. Either bacteria or large particles in the fecal stream cause the inflammation. EN probably works by limiting the fecal stream, and its bioavailability depletes intestinal bacteria from the necessary nutrients to survive.

I wrote this in 2019.

Now we have some proof to substantiate this.

Treatment of Active Crohn's Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products
2024 Jul

School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom.

Caroline Kerbiriou 1 , Caitlin Dickson 1 , Ben Nichols 1 , Michael Logan 1 , Anna Mascellani 2 , Jaroslav Havlik 2 , Richard K Russell 3 , Richard Hansen 4 5 , Simon Milling 6 , Konstantinos Gerasimidis



Background: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN.

Methods: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing.

Results: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi.

Conclusions: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.

 

[kiny]

Bacterial metabolites like butyrate are not protective against intestinal inflammation, neither in CD nor in UC, and just like unfermented b-fructan and prebiotic fibers, they have shown to cause harm by exacerbating inflammation.

Neither fecal transplants, probiotics, nor fiber intake, are helpful in treating crohn's disease. It is increasingly clear they are pro-inflammatory in crohn's disease patients.

It is absence of fiber in EN, and deprivation of nutrients, that limits bacterial growth potential and inflammation. The presence of fiber stimulates bacterial growth, inflammation, and an immune response to bacterial metabolites.

Dieticians, especially those for crohn's disease, need to be aware of this.

 

[kiny]

The ability of exclusive EN to decrease inflammation is astounding. No treatment comes even remotely close to the effectiveness of EN.

1447×798
234,2 kB

 

[Opieshuffle13]

So... based on all of the above, would it suggest that going EEN even while in remission is a good way to rebalance the gut microbiome? I just had my 2nd resection at 56 and I don't ever want this to come back. I'm on Stelara and so far so good, but based on the above, would it HELP to go EEN to help balance the guts? I only ask because things are still in disarray 8 months after surgery. Maybe this is my new normal, but I wonder if there's "a disturbance in the force" as it were...

 

[kiny]

All this data doesn't agree that there is such a thing as a healthy microbiome. High bacterial and fungal load, bacterial metabolites, Butyrate, SCFAs, the dietary consumption of fiber and fermenation, are all detrimental to crohn's disease patients and leads to inflammation.

Even in the colon, where bacterial load is extremely high, butyrate leads to an increase in inflammation in UC patients, it is not protective. https://pubmed.ncbi.nlm.nih.gov/30919886/

Fecal transplants of healthy controls transplanted to some crohn's disease patients have lead to a worsening of inflammation. Probiotics have been shown to be unhelpful, if not detrimental for crohn's disease patients.

To me this is not surprising, animals with transient microbiomes and low bacterial load have few intestinal disorders. The microbiome does not seem protective, or beneficial. Crohn's disease would not exist if the environment was more sterile.

EN does not "restore" a microbiome, EN is highly dysbiotic, it is free of fiber and leads to a decrease in bacterial load, SCFAs, butyrate, and fiber fermenting bacteria. It moves further away from a microbiome found in healthy controls. Yet, it leads to rapid remission and a healthier intestine.

To accept this, one has to consider that there is no such a thing as a healthy microbiome, data increasingly shows this. Which is hard to do, because people have been taught the opposite for decades.

The microbiome is not our friend. While still a minority, a rapidly growing number of voices in the scientific community agree. The data associating health benefits with the microbiome is not reliable, and animals with transient microbiomes do not suffer from some of the intestinal disorders found in humans or animals with resident microbiomes.

 

[kiny]

The acceptance that the microbiome is often very detrimental and can lead to disease is slow, it requires admitting that a lot of research was very wrong.

When broad spectrum antibiotics cause large changes in the microbiome-mycobiome relationship, we somehow only put the blame on the antibiotics.

No one seems to question the fact these biomes have such a high pathogenic potential, and are to blame too.

If the microbiome is so beneficial, why does it have such potential for disease.

When pathogens such as invasive E coli and Enterococcus, considered harmless commensals by some prior, are now shown to cause disease, they should be called disease-causing pathogens.

But a lot of researchers have issues calling a spade a spade. So they end up using terms like "conditionally pathogenic", or "pathobionts". No, they're pathogens, they cause disease, and damn serious disease, the research was wrong. Call a spade a spade.

 

[Pangolin]

I've always understood the idea of a "beneficial" microbiome not so much the idea that we gain any benefits per se from "good" bacteria as the idea that some bacteria are worse than others, and certain "good" bacteria can benefit us simply by outcompeting any pathogenic bacteria while not causing disease themselves. In other words, the sole benefit of the "good" bacteria is simply crowding out the "bad" bacteria and not otherwise causing problems.

A sterile gut environment may be even better, but we have good evidence that this bacterial competition model is the case in some situations such as c diff infections. Of course, Crohn's doesn't seem to benefit from attempts at changing the microbiome, aside from reducing it.

 

[Opieshuffle13]

I guess I'm just frustrated that between my second re-section and previous gall bladder removal, an over abundance of bile and food interactions continues to wreak havoc on my system. No amount of Bile sequestrants seems to control it, and I was wondering if the whole system was out of whack, hence the questions about a "re-set" to the biome. Time to start an elimination diet and see if I can find any big triggers. So many of the Chrohn's diets don't work for me. Anyway... thanks for the detailed explanations @kiny.

 

[kiny]

Changes in metabolites after treatment with EN are increasingly well documented. Large alterations in concentrations of SCFAs , bile acids , butyric acids, and sulfide.

But just because we see changes in bacterial metabolites concentrations, doesn't have to mean these are due to changes in bacterial composition. EN is a highly bioavailable liquid diet, this will cause major changes in absorption and the fecal stream, and will change metabolite concentrations irrespective of changes in bacterial composition. I would like to see the effect on these metabolite concentrations, simply after a liquid diet. EN could simply also be stopping a feedback loop where it stops excessive bile in the stool for example, again, irrespective of bacterial composition, bacteria simply initiate this loop, but inflammation keeps it in motion, and EN causes resolve.

What also happens is a change in fecal pH when you use EN. Fecal pH in the distal small bowel of crohn's disease patients on a regular free diet tends to be slightly lower compared to healthy controls, maybe due to malabsorption or differences in fermenation of carbohydrates. However, EN treatment, which has a specific carbohydrate profile, increases fecal pH very significantly and turns it alkaline. I posted a study in the past where fecal pH of children on EN increased to 7.9 during EN treatment, significantly above controls on a free diet and signficantly higher than pre-EN treatment. What the significance of this is, I don't know, but not all bacteria can grow at these alkaline pH values.

 

[wild_one353]

I guess I'm just frustrated that between my second re-section and previous gall bladder removal, an over abundance of bile and food interactions continues to wreak havoc on my system. No amount of Bile sequestrants seems to control it, and I was wondering if the whole system was out of whack, hence the questions about a "re-set" to the biome. Time to start an elimination diet and see if I can find any big triggers. So many of the Chrohn's diets don't work for me. Anyway... thanks for the detailed explanations @kiny.

look into studies on low fat diets(which would reduce the production of bile) and fiber from food or soluble fiber supplements, which would bind to bile acids. Psyllium or pectin supplements might help. Taking them at the same time as a meal could help a bit. Fiber from food is likely safer and more beneficial.

link that might help https://crohnsandcolitisdietitians.com/how-can-nutrition-help-with-bile-acid-malabsorption/