IBS

2) Inflammation

In some sense, IBS may be considered IBD-lite, which means it’s like IBD (Crohn‘s, colitis), but with lower levels of inflammation.  Patients with IBD experience IBS-like symptoms when their IBD cools down.  (R)

A three-year study found that patients diagnosed with IBS were 16.3 times more likely to be diagnosed with IBD during the study period. (R)

The risk of developing IBS increases sixfold after acute gut infection.  (R)  After salmonella, risk increases by 8X (R). This is because infections cause inflammation (and oxidative stress).

Inflammation can affect the gut in many ways.  One way is by activating our stress response/HPA axis. (R)

Most of my clients with IBS also are more stressed than the general population – not because they are stressed out people, but because inflammation activates the stress pathway, which causes more physiological stress.

People with IBS likely have immune reactions to dietary proteins, as food elimination based on IgG antibodies has been found to result in a significant decrease in symptoms of IBS. (R)

Mast cells have been shown to be increased in intestinal mucosa in patients with IBS, especially by intestinal nerves. (R)

Mast cells directly influence gut flow and results in an increase in abdominal pain and discomfort  (R).

Various markers of inflammation have been found to be elevated in people with IBS.

There’s evidence that anti-inflammatory drugs such as Mesalazine help treat IBS. Mesalazine helps to normalize the gut flora and reduce gut permeability. (R) Anti-inflammatory supplements should work as well.

A wide variety of inflammation types can cause IBS.  There’s no one cytokine that’s dominant.

Even if the inflammation isn’t always systemic, it could still be localized.  However, most/all of the cited studies are measuring elevated systemic inflammation.

This is less reliable than if you were to actually measure the inflammation in your gut tissue.  Local inflammation would likely be much worse.

People with IBS are more like to have:

• Th1 Dominance – people with IBS are more likely to be Th1 dominant (elevated IL-12) (R).  Interferon reduces serotonin in the gut and also increases oxidative stress (by activating IDO) (R).  However, people with Th2 can also have IBS because of Mast cells and other types of inflammation.
• Th17 Dominance (R)
• Th2 Dominance (R)- Th2 cytokines quicken gut flow. Stimulated IL-5, IL-13are higher in IBS.
• Higher TNF (R, R2) – especially IBS-D (R)
• Higher IL-1b (R)
• Higher IL-6 (R, R2) – capable of stimulating gut neurons (R)
• Higher CRP – People with IBS have an average hs-CRP of 1.17, while healthy controls have a level of 0.72 (R). Your doctor wouldn’t blink at this difference, but the science begs to differ.
• Higher IL-8 (R)
• High Nf-kB Activation (R)
• Low Tregs (Tregs decrease general inflammation) (R)
• Low IL-10 (an anti-inflammatory cytokine) (R) – especially in males (R)
• TGF-b – Intermediate producers (R)
• Mast Cell Activation and increased Lymphocytes in the mucosa and lamina propria  (R).  Mast cells were higher in IBS-D patients than healthy volunteers (9.6 vs. 5.7).(R)

Taking a good Probiotic can counteract the inflammation, as well as anti-inflammatories recommended in the linked articles.

If you click on the linked articles, you’ll see I’ve done a lot of research into each parameter of inflammation and how to combat it.

3) Oxidative Stress

In people with IBS, markers of oxidative stress were significantly higher – specifically, blood levels of xanthine oxidase (XO), adenosine deaminase(AD), malondialdehyde (MDA) and nitric oxide (NO).

The enzymes that break down oxidants were significantly lower (Superoxide dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GPx). (R)

These changes are in part genetic, but they can be overcome with the right environment (and supplements if needed).

4) Serotonin

Most of the serotonin in the body (95%) is found in your gut. (R)

Serotonin quickens gut flow by speeding up motor neurons and it releases chloride.

Serotonin cells were significantly higher in IBS-D and lower in IBS-C than in controls. (R)

This makes sense.  If there’s less serotonin, constipation will occur and if there’s too much, diarrhea will occur.

In particular, there were small numbers of serotonin-containing in the small intestine, which means the flow is slowed. (R)  This is why bacteria can build up in the small intestines.

Serotonin transport is also reduced in patients with IBS, possibly because of interferon gamma (Th1). (R,R2)

5) Low cyclic AMP

cAMP is a molecule that is an important second messenger for cellular communication.

cAMP has so many roles in the body, one of which is increasing gut flow (R).

6) Low cyclic GMP

Like cAMP, cGMP is an important second messenger for cellular communication.

cGMP helps blood vessels, lungs, insulin secretion, and gut flow (R).

Not getting enough sun will cause lower nitric oxide, which will lead to lower insulin release.  People with slower gut flow generally don’t get enough full body sun.

7) Excess IDO, Low Tryptophan

The enzyme IDO1 degrades tryptophan into kynurenine and is needed to create Tregs (Good).  (R)

However, IDO1 may sustain self-attacking antibody production by B cells (Bad), and cause cancer in the context of chronic inflammation. (R)

IBS is believed to be caused by too much IDO, and therefore too much conversion of tryptophan to kynurenine (instead of to serotonin).  (R)

The conversion of tryptophan to kynurenine causes too much oxidative stressin the gut and too little serotonin.  (R)

High Kynurenine and low tryptophan is a good marker for IBS, but this imbalance is found in other inflammatory conditions, so it’s not specific.  (R)

Inflammation from Interferon gamma (Th1 cytokine) or LPS from bacterial infections will increase IDO. (R)

Studies have found that interferon gamma increases in the small intestine after consuming gluten (by gluten-sensitive patients without coeliac disease). (R)

COX-2 inhibitors decrease IDO. (R)

IBS AND THE GUT IMMUNE SYSTEM:

AhR is a receptor in gut cells that helps the development of tolerance to proteins and also curbs the growth of bad bacteria (candida) by producing antimicrobial peptides. It regulates the number of Tregs, cytotoxic T cells, B cells and mast cells.  (R)

Too little activation of this gut immune system may result in autoimmunityand allergies. (R)

Good bacteria (LAB such as L Reuteri) eat tryptophan as a source of energy and produce molecules that activate AhR.  (R)  Kynurenine also activates AhR. (R)

This curbs the growth of Candida and boosts the growth of good bacteria (lactic acid bacteria). (R)

Without tryptophan in their ‘diet’, microbes do not produce molecules that activate AhR (IAld).  This results in less good bacteria (lactobacilli) and more bad bacteria (Candida), which is typical of IBS. (R)

Tryptophan supplementation may increase levels of serotonin and AhR activation (both good).  (R)

However, it’s a double-edged sword because tryptophan metabolism will cause oxidative stress.  (R)

Adding antioxidants with tryptophan is one approach to getting around this.

Cruciferous veggies contain indoles, which activate AhR. This contributes to a favorable microbial environment in the stomach. (R)

A variety of herbal extracts such as ginseng, licorice, gingko Biloba results in AhR activation. (R)

AhR activation is not always positive, as it can activate mast cells. (R)

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