Irritable Bowel Syndrome is a diagnosis of exclusion, which means that doctors diagnose this issue after eliminating all the other possibilities. Several doctors believe that IBS is a psychogenic or “in your head” problem, with unknown causes. Most IBS patients have normal bloodwork and other tests, and the treatments are often limited to just adding fiber or increasing water intake.
I personally dealt with IBS myself when I struggled with many health issues. Interestingly, I found a lot of studies examined the causes of IBS, which are summarized in this post.
Lab Test Analyzer is the tool I wish I had when I was dealing with all my health issues. Instead of normal, it will tell you the optimal values of your labs that come back normal. And if you are outside the optimal range, it will give you actionable tips and recommendations that will help you get there.
- Introduction and Summary
- 1) Stress and IBS
- 2) Inflammation
- 3) Oxidative Stress
- 4) Serotonin
- 5) Low cyclic AMP
- 6) Low cyclic GMP
- 7) Excess IDO, Low Tryptophan
- 8) Microbial Imbalance: Lack of Good Gut Bacteria, Excess Bad Bacteria
- 9) Intestinal Permeability
- 10) Bad Diet: Excess Sugar
- 11) FODMAPs
- 12) TGR5 and Bile
- 13) Undiscovered Infection
- 14) Antibiotic Usage
- 15) Low Stomach Acidity
- IBS and Hormones
- Monitoring Your Hormones
- Excluding Other Conditions
- IBS is Commonly Found With:
- Irregular Blood Test Results?
Introduction and Summary
Ask your doctor about the cause of IBS and they will likely give you a blank stare.
The 3-minute assembly line churns and since you aren’t about to die, it’s on to the next case.
The NIH estimates that as many as 20% of Americans may experience signs of IBS. (R)
As you will see, IBS is a complex disease and there are many variables in the web of causes.
There are two main types of IBS – one that involves Diarrhea (IBS-D) and one that involves Constipation (IBS-C).
- Contractions (flow) that is too fast cause diarrhea predominant (IBS-D)
- Contractions that are too slow cause constipation-predominant IBS (IBS-C).
Food goes from your stomach to your small intestine, where it’s broken down into carbohydrates, fats, and proteins. Only simple sugars (glucose, fructose, galactose and mannose) can be absorbed into your bloodstream.
The carbohydrates that aren’t broken down or absorbed pass to your large intestine, where bacteria ferment them. Fermentation produces gas, which is normal. This fermentation is supposed to occur only in your large intestine.
So food goes from stomach-> small intestine->large intestine.
The large intestine is loaded with bacteria, but the rest of your gastrointestinal tract has relatively few bacteria. You are not supposed to have large amounts of bacteria in your small intestine.
When a person has bacteria in the small intestine, unabsorbed carbohydrates are fermented there, producing significant amounts of gas.
This causes cramping and burning because the gas stretches the small intestine. The gas can also push the intestinal contents rapidly toward your large intestine to cause diarrhea.
Bacteria generally ferment in your small intestines because your gut ‘flow'(motility/peristalsis) is slowed down in this area.
When people have diarrhea, it usually means the flow is quickened in the large intestine.
Gut pain comes from the neurons in your gut being ‘hypersensitive’, and this has many causes as you will see.
When your intestines expand, this is sensed by the neurons in your gut. If your neurons are hypersensitive, this distension will feel uncomfortable or hurt. Others will just feel bloated, but not pain.
One major cause of gut flow changes is because we have too little serotonin. Why? Because the gut immune system is imbalanced.
This post is mainly about IBS, but other gut problems are often from the same causes.
1) Stress and IBS
Chronic stress response activation (HPA) is believed to be a causal factor of anxiety disorders, bipolar, insomnia, PTSD, borderline personality, ADHD, major depression, burnout, chronic fatigue syndrome, fibromyalgia, IBS, alcoholism and other diseases. (R)
Chronic stress is probably the most common and significant cause of gut flow (motility) changes.
Your gut is lined with these motors (neurons) that move things along at a steady pace.
CRH is a direct cause of IBS by increasing the flow or motor speed in the colon and decreasing it in the small intestine. When the flow is decreased in the small intestine, bad bacteria overgrow by feeding on carbs. (R) This results in gas from the ass.
When motility is increased in the colon, that could cause diarrhea.
People who get IBS are more susceptible to gut dysfunction when CRH is released (R).
In IBS, there are increased HPA axis responses to stressors such as meals, hormones and mental stress compared to controls. (R)
Therefore, stress is more harmful to people with IBS with regard to gut function.
CRH also causes your gut to be ‘hypersensitive’ and experience pain more. When given a drug that blocks CRH, the pain goes away. (R)
CRH does many other bad things such as:
- Decreased slow wave sleep. (R)
- Increases inflammation – increases Th1 dominance, Nf-kB, IL-1b (by 8.5X), IL-6 (7.3X), TNF (13X), MHC-II (HLA-DR) and ICAM-1 expression. Max inflammation was reached in an hour. (R) Also increases TLR-4 (a significant source of inflammation), including in the intestines. (R)
- Causes autoimmune diseases. In rheumatoid arthritis, Hashimoto’s and UC, inflamed tissues contained large amounts of CRH. (R) In a mouse model of arthritis, blocking CRH reduced inflammation and markers of cartilage destruction. (R)
- Activates mast cells – and therefore histamine issues, which explains in part why stress induces allergic symptoms. (R) See my post on combatting histamine.
Stress will also cause the release of various neurotransmitters (catecholamines), which decreases intestinal flow. (R)
I recommend putting a device called ICES on your head to decrease CRH and inflammation.
In addition, they cause a short-lived increase in blood pressure, but a long term decrease in blood pressure. They also cause sedation and thicker blood (platelet aggregation) (R).
These are all symptoms that are more common in people I see who have IBS-C.
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)
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-13 are 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).
These changes are in part genetic, but they can be overcome with the right environment (and supplements if needed).
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.
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.
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
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)
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)
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 autoimmunity and allergies. (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)
AhR activation is not always positive, as it can activate mast cells. (R)
8) Microbial Imbalance: Lack of Good Gut Bacteria, Excess Bad Bacteria
Individuals with IBS have been found to have decreased diversity and numbers of bacteroidetes microbiota.
Fecal microbiota transplant has a ‘cure’ rate of between 36 percent and 60 percent. (R)
The nonabsorbed antibiotic rifampin can provide sustained relief for some IBS patients. This could be because it prevents the overgrowth of small intestinal flora. (R)
In all mammals (our animal relatives) tested, they were found to have L reuteri in their guts.
With humans, L Reuteri is found in only 10-20% of people. It’s likely that we once had this in our guts, but with our shitty diets and lack of fermented veggie, most of us don’t now.
L reuteri switches consumption from sugar to tryptophan and produce the molecules for our gut protection (AhR ligands – 3-IAld).
L Reuteri increases gut motility and decreases pain perception. (R)
Clay has been found to be beneficial, likely because of its antimicrobial and laxative properties. (R)
9) Intestinal Permeability
If you’ve been reading the blogosphere, you’ll know by now that gut permeability has to do with every disease in existence – and even in diseases not in existence such as adrenal fatigue.
Well, the whole gut permeability spiel is overdone, but there’s some truth to it.
IBS and IBD are in part caused by gut permeability. (R)
Stress increases gut permeability. (R)
In animal models, both acute and chronic stress enhance the ability of bacteria to adhere, internalize and cross over your gut, which causes gut inflammation. (R)
Hypersensitivity from stress results from an alteration of colon permeability. (R)
Lectins and gluten may also cause gut permeability (R, R). I personally beat my IBS once I avoided lectins and FODMAPs. In order to figure out the best diet for you, consider trying the Lectin Avoidance Diet. It is a protocol that helps you figure out the food items that may trigger your symptoms.
10) Bad Diet: Excess Sugar
When bacteria in our gut consume sugar, they stop producing molecules (AhR ligands) that are necessary for our gut protection against pathogens such as candida. (R) These bad pathogens then overgrow.
When sugar is the energy source for our gut microbes, they stop consuming tryptophan and serotonin is reduced. Serotonin is necessary for proper gut function. (R)
So stay away from added sugars.
Also, added sugars, sugared drinks, and foods made from flour (bakery products and pasta) are the ones that are most easily fermented by bacteria to cause intestinal gas.
A lack of plants or natural antimicrobials contributes to the bacteria in your gut.
FODMAPs are fibers that result in fermentation and associated gas production, which causes gut distension and bloating.
One of the most evidenced-based treatments for IBS is to restrict FODMAPs. (R)
Leafy greens and cucumbers are low FODMAP veggies that I enjoy.
Bottom Line: FODMAPS+CRH=Gut pain.
12) TGR5 and Bile
TGR5 and its activation by bile acids speed up the gut flow. (R)
Mice without TGR5 have leaky gut. (R)
Therefore, a deficiency of bile could lead to IBS-C and too much bile could lead to IBS-D. (See below for variations in the TGR5 receptor). (R)
Indeed, up to 30% of people with IBS-D have bile acid malabsorption (which is a different condition, but the results are similar: diarrhea). These people do well with bile acid sequestrants. (R)
If you have IBS-C then you should consider taking Ox Bile to activate TGR5.
13) Undiscovered Infection
Research supports IBS being caused by an as-yet undiscovered active infection.
The nonabsorbed antibiotic rifampin can provide sustained relief for some IBS patients. This could be because it kills an undiscovered microbe (or because it reduces overgrowth of intestinal flora). (R)
Other researchers have focused on a possible unrecognized protozoal infection such as blastocystosis as a cause of IBS, as certain protozoal infections occur more frequently in IBS patients. (R)
14) Antibiotic Usage
Antibiotics can contribute to intestinal overgrowth by killing your good bacteria.
Antibiotic usage increases the risk of developing IBS. (R)
However, some antibiotics like rifaxamin can be beneficial, probably because it’s selective against only certain bacteria.
15) Low Stomach Acidity
Stomach acidity prevents the growth of bacteria. Although neutralized when it goes to the small intestine, if your gut isn’t acidic, more bacteria will grow in your intestines.
IBS and Hormones
Monitoring Your Hormones
Sometimes, a lab result may be in the reference range, but not actually be in the optimal range. Reference ranges are not the same as optimal ranges. This is why even hormones in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal. Lab Test Analyzer will let you know if your hormone levels are optimal and what you can do to get them there if they aren’t.
16) Low T3
Adequate T3 (the active thyroid hormone) allows for the absorption of carbs in the intestines and also controls your gut flow.
If you have low T3, fewer carbs will be absorbed and your gut flow will decrease. Both of these result in increased fermentation of bacteria in your small intestines.
17) Excess CCK
CCK is the culprit that causes gas soon after eating. (R) This might be because of activation of the vagus nerve or because CCK directly interacts with the hypothalamus to stimulate the flow of your colon, which will cause gas. (R)
18) Excess Cortisol
I already spoke about CRH being a cause of IBS. But cortisol may also be involved.
Cortisol was generally higher in the morning and lower in the evening than healthy controls. (R)
When researchers evaluated the psychological stress of the subjects, they found that the higher Cortisol levels in IBS could not be explained by differences in psychological stress. (R)
19) Sex Hormones: Testosterone, Estrogen, Progesterone
Estrogen and progesterone receptors are in your gut. (R)
Both women with and without IBS are more likely to experience
symptoms such as stomach pain, diarrhea, nausea, and bloating when estrogen and progesterone drop down to the lowest levels in the body (during the menses). (R)
During the low estrogen and progesterone phase (menses), women with IBS are more sensitive to gut pain. (R)
Bloating also seems to be worse during the phase associated with higher progesterone (the luteal phase). (R)
Women tend to experience a decrease in IBS during menopause, where estrogen and progesterone decline. (R) This indicates that the hormones may not have as much to do with IBS as does their fluctuation.
20) Decreased Motilin
People with IBS have decreased motilin response to both a meal and water. (R)
However, they show an increase in motilin in response to mental stress and this causes abnormally increased gut activity. (R)
Studies suggest that pH in the beginning of the small intestine (duodenum) affects motilin release. (R)
Low pH (acidic) inhibits motilin and gastric motor activity, whereas a high pH (alkaline) it has a stimulatory effect. (R)
This is one culprit that causes gas soon after eating. (R)
21) Excess VIP
VIP stimulates the secretion of water and electrolytes, bicarbonate and pepsin (an enzyme). It inhibits gastric acid secretion. (R)
VIP stimulates the bowels and can cause crampy and watery diarrhea when highly concentrated in the gut. (R)
In two studies, VIP was twice as concentrated in IBS patients compared to control subjects. (R)
In another study, VIP was only high in women with IBS-D. (R)
22) Low PYY
PYY stimulates absorption of water and electrolytes and inhibits PGE2 and VIP, which stimulates intestinal fluid secretion. (R)
It acts to slow down the small intestines.
PYY cells are reduced in both IBS-D and IBS-C. (R)
In people with IBS, Ghrelin and motilin are more in sync and vary with each other. (R)
The Obestatin/Ghrelin ratio also has some significance. (R)
24) Secretin, GIP
In IBS-diarrhea patients, there are fewer cells that release CCK, secretin, GIP, and somatostatin. (R)
These hormones stimulate bicarbonate, enzyme secretion, and gall bladder contraction (CCK). (R)
Secretin, GIP, and somatostatin inhibit stomach acid secretion, so having too little of them could result in excess stomach acid release. (R)
25) Low Oxyntomodulin
Oxyntomodulin cells were significantly lower in both IBS-D and IBS-C than controls. (R)
Somatostatin cells were significantly lower in the IBS-D groups, but higher in IBS-C patients than in the controls. (R)
27) Excess Substance P
Substance P was also elevated in people with IBS (0.11 vs. 0.03). (R)
29) Defective Mucus Layer
The mucus layer in your gut is an important barrier to keep out the microbes in your gut. If it’s not functioning properly (not enough mucin (R)), bacteria will cross over, cause inflammation and this will also change your gut microbiota for the worse. It can also alter the intestinal structure. These changes are common in IBS. (R)
30) Guanylate cyclase 2C
Guanylate cyclase 2C is a receptor in your gut cells that influences gut flow. When it’s activated, it speeds it up. A drug called Linaclotide does just that (FDA approved in 2012 for IBS-C). (R)
Linaclotide reduces activation sensory neurons in the colon, reducing pain. 50% of those receiving linaclotide saw a significant reduction in pain, versus 37% with the placebo. (R)
Linaclotide activates colonic motor neurons, which increases gut flow and thus promotes bowel movements. (R)
31) Nutrient Deficiencies
32) Lack of Soluble Fiber
Some evidence suggests soluble fiber supplementation (e.g., psyllium husk) is effective for IBS. (R)
For IBS-D, it allows for a more consistent stool. For IBS-C patients, it seems to allow for a softer, moister, more easily passable stool. (R)
However, insoluble fiber (e.g., bran) has not been found to be effective for IBS and may aggravate symptoms in some. (R)
Fiber is especially beneficial in those with IBS-C. Soluble fiber can reduce overall symptoms, but will not reduce pain. (R)
A meta-analysis found only soluble fiber improved global symptoms of irritable bowel, but neither type of fiber reduced pain. (R)
Studies have used 10–30 grams per day of psyllium. (R)
33) Fat Malabsorption
About 30% of IBS patients have fat malabsorption. (R)
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SelfDecode has a page on the genetics of IBS. It’s the best genetic program to analyze your genes, so buy your 23andme ($99) and sign up.
There are many genes that can contribute to IBS. These are just a few examples to give you an idea.
IBS/IBD individuals are less often HLA-DQ 2/8 positive than in healthy populations.(R)
People with a genetic predisposition to produce higher TNF are more likely to have IBS and IBD.
The Glycine transporter (GLYT1) is essential for the protection of gut cells against oxidative damage. This is controlled by the SLC6A9 gene (rs3791124 -AG is bad and AA is terrible). The majority of clients with gut problems have a mutation in this gene.
Excluding Other Conditions
Conditions with IBS-like symptoms include parasitic infections, lactose intolerance, SIBO and celiac disease. (R) However, SIBO goes hand and hand with most cases of IBS, so I wouldn’t necessarily consider them separate diseases.
The following investigations should be performed to exclude other conditions (R):
- Stool microscopy and culture (to exclude infectious conditions)
- Blood tests: Full blood examination, liver function tests, erythrocyte sedimentation rate, and serological testing for coeliac disease
- Abdominal ultrasound (to exclude gallstones and other biliary tract diseases)
- Endoscopy and biopsies (to exclude peptic ulcer disease, coeliac disease, inflammatory bowel disease, and malignancies)
- Hydrogen breath testing (to exclude fructose and lactose malabsorption)
IBS is Commonly Found With:
Several medical conditions appear with greater frequency in patients diagnosed with IBS.
- 94% of IBS patients have psychiatric disorders -most commonly anxiety and depressive disorders. (R)
- IBS occurs in 51% of chronic fatigue syndrome patients and 49% of fibromyalgia patients. (R)
- IBS occurs commonly with migraines and headaches. (R)
Irregular Blood Test Results?
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