Stress as the cause of Crohn’s Disease?

[Mito]

“Researchers have identified a possible link between psychological stress and Crohn's disease. In a study led by Canada's McMaster University and the Farncombe Family Digestive Health Research Institute, and published in the journal Nature, the authors said that mouse models found that stress hormones suppressed the innate immune system that normally protects the gut from Enterobacteriaceae.”

Abstract​

Crohn’s disease is an inflammatory disease of the gastrointestinal tract characterized by an aberrant response to microbial and environmental triggers. This includes an altered microbiome dominated by Enterobacteriaceae and in particular adherent-invasive E. coli (AIEC). Clinical evidence implicates periods of psychological stress in Crohn’s disease exacerbation, and disturbances in the gut microbiome might contribute to the pathogenic mechanism. Here we show that stress-exposed mice develop ileal dysbiosis, dominated by the expansion of Enterobacteriaceae. In an AIEC colonisation model, stress-induced glucocorticoids promote apoptosis of CD45+CD90+ cells that normally produce IL-22, a cytokine that is essential for the maintenance of ileal mucosal barrier integrity. Blockade of glucocorticoid signaling or administration of recombinant IL-22 restores mucosal immunity, prevents ileal dysbiosis, and blocks AIEC expansion. We conclude that psychological stress impairs IL-22-driven protective immunity in the gut, which creates a favorable niche for the expansion of pathobionts that have been implicated in Crohn’s disease. Importantly, this work also shows that immunomodulation can counteract the negative effects of psychological stress on gut immunity and hence disease-associated dysbiosis.

Psychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts - Nature Communications

Altered gut microbiome and exacerbation of symptoms at times of psychological stress are feature characteristics of Crohn’s disease. Here authors show in a mouse model that psychological stress impairs IL-22-dependent protective immunity of the ileal mucosa, which allows invasive bacteria to...

www.nature.com

 

[haidut]

stress-induced glucocorticoids promote apoptosis of CD45+CD90+ cells that normally produce IL-22, a cytokine that is essential for the maintenance of ileal mucosal barrier integrity

And now consider that glucocorticoids are still a major portion of "treating" IBD (and other autoimmune conditions), at least as an add-on and as a single-therapy during acute exacerbations. I have no idea how this homicidal house of cards is still standing...

 

[Thedumbass]

​

This has been known for quite a while and anyone who has crohn's will tell you stress creates a sickening feeling in your gut and a flare or symptoms follow shortly. There is an excess of Corticotropin releasing hormone that I believe is a cause.
If anyone knows of some thing that suppresses crh production let me know I'm curious to try it.

Corticotropin-releasing hormone; corticotrophin-releasing factor; corticotropin-releasing factor; corticoliberin; CRH; CRF

Corticotrophin-releasing hormone also acts on many other areas within the brain where it suppresses appetite, increases anxiety, and improves memory and selective attention. Together, these effects co-ordinate behaviour to develop and fine tune the body’s response to a stressful experience.

Finally, in smaller quantities, corticotrophin-releasing hormone is also made by certain white blood cells, where it stimulates swelling or tenderness known as inflammation, particularly of the gut.

Abnormally high corticotrophin-releasing hormone levels are connected with a variety of diseases. Because it stimulates anxiety and suppresses appetite, too much corticotrophin-releasing hormone is suspected of causing nervous problems such as clinical depression, anxiety, sleep disturbances and anorexia nervosa.


In addition, high levels of corticotrophin-releasing hormone may also make certain inflammatory problems worse, including rheumatoid arthritis, psoriasis, ulcerative colitis and Crohn's disease. Initially this might seem unexpected because raised levels of corticotrophin-releasing hormone in the brain can lead to increased glucocorticoids production, and glucocorticoids have an anti-inflammatory effect. However, research has revealed that when high levels of corticotrophin-releasing hormone occur in tissues outside the brain, they can actually have a powerful inflammatory action. Increased corticotrophin-releasing hormone levels within the joints, skin or gut can therefore make these inflammatory conditions worse or even play a role in their development.

Reference

Corticotrophin-releasing hormone | You and Your Hormones from the Society for Endocrinology

Corticotrophin-releasing hormone is the main element that drives the body's response to stress. It is also present in diseases that cause inflammation. Too much or too little corticotrophin-releasing hormone can have a range of negative effects.

www.yourhormones.info

 

[jondoeuk]

There is evidence that suggest changes in the gut microbiota in patients with IBD. These over activate local mucosa immune cells leading to chronic inflammation and mucosal lesions. A substantial proportion of patients do not respond to the currently available treatments, most of them immunosuppressive drugs with potential long-term negative consequences. Consequently, ''alternative'' and safer therapies are being studied, such as fecal microbiota transplantation. Despite all the human clinical data, the FDA only allows the use of it for recurrent C. difficile, but still has tighter restrictions for IBD, including Crohn's.

 

[Thedumbass]

There is evidence that suggest changes in the gut microbiota in patients with IBD. These over activate local mucosa immune cells leading to chronic inflammation and mucosal lesions. A substantial proportion of patients do not respond to the currently available treatments, most of them immunosuppressive drugs with potential long-term negative consequences. Consequently, ''alternative'' and safer therapies are being studied, such as fecal microbiota transplantation. Despite all the human clinical data, the FDA only allows the use of it for recurrent C. difficile, but still has tighter restrictions for IBD, including Crohn's.

Yes a bad microbiom can cause crohn's.
For example this case study demonstrates an iron dependent bacteria as the cause and treats it with great success.
Mycobacterium, including MAP, are iron-dependent bacteria, and gallium (Ga) is bacteriostatic to them.
For some reason the original George eby link is missing and this is the only one I can find.

Is Gallium Nitrate a Treatment Or a Cure for Crohn S Disease? a Case History and Hypothesis

Is Gallium Nitrate a treatment or a cure for Crohn s Disease? A Case History and Hypothesis. George A. Eby III George Eby Research Institute 14909-C Fitzhugh Road Austin, Texas 78736 Telephone 1-512-263-0805 Email.

docest.com

But I don't believe that it is the only cause.

 

[haidut]

If anyone knows of some thing that suppresses crh production let me know I'm curious to try it.

The role of CRH in autoimmune conditions is more well-known and is now being studied in MS, Parkinson, Alzheimer, etc. However, this study showed that it was the glucocorticoids (e.g. cortisol) themselves that are problematic too and I would say that is certainly not well-known to most doctors working in that field. They would pump a person full of glucocorticoids any chance they get. The more modern drugs for autoimmune conditions are just more selective immunosuppressants than glucocorticoids, but still the same in terms of core/systemic effects.
As far as blocking CRH, pregnenolone and progesterone are probably the strongest endogenous agents that can do that.

Pregnenolone Is The Most Potent Inhibitor Of The Stress Signal (CRH)

I think this study should finally put to rest the arguments and debates of whether pregnenolone raises or lowers cortisol, and how it affects the stress response overall. I posted a similar study, which showed that the pregnenolone metabolites progesterone and allopregannolone potently inhibited...

raypeatforum.com

 

[Thedumbass]

Thank you!

 

[Sefton10]

Mainstream starting to pick up on the impact of the environment and diet

“Human genetics hasn’t altered over the past few decades,” said Lee, who was previously based at Cambridge University. “So something must be changing in the outside world in a way that is increasing our predisposition to autoimmune disease.”

Global spread of autoimmune disease blamed on western diet

 

[DaveFoster]

As a side note, IL-22 is upregulated in rats with deficiency of the intestinal protein mucin-2, indicating enhanced immunity. Aspirin may be an effective facilitator of such, as it lowers the level of mucin-2. One would expect a lowered incidence of Crohn's disease in patients who take aspirin regularly.

References
Hartmann P, Seebauer CT, Mazagova M, et al. Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity. Am J Physiol Gastrointest Liver Physiol. 2016;310(5):G310-322. doi:10.1152/ajpgi.00094.2015