IBS

17) Excess CCK

People with IBS are more likely to release too much CCK (a gut hormone) in response to a fat-rich meal.  (R)
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 is unusually high in women with IBS.  (R)
This is probably because we know that CRH causes significantly more ACTHto be released in people with IBS when compared to people without IBS. (R)
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

Low estrogen and progesterone play an important role in IBS. (R)
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.
Testosterone is capable of increasing pain hypersensitivity. (R)

20) Decreased Motilin

Motilin is a hormone that stimulates the gut flow and is normally decreased after meals but increased in between meals or fasting.  Insulin inhibits motilin. (R)  Motilin stimulates the gut flow.
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 intestines. (R)
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)

23) Ghrelin

Ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls. (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)

26) Somatostatin

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)

28) TRH

TRH is the precursor to TSH and acts to stimulate gut flow and this is dependent on stimulation of the vagus nerve. (R)  This can worsen IBS-D.

Other

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

Vitamin D deficiency may contribute to IBS and some case reports show improvement in symptoms. (R)
A low intake of vitamin B6 is correlated with worse symptoms of IBS. (R)

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)

Genetics

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.
INFLAMMATION:
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 (A) allele of TNF-308 (rs1800629) is associated with higher levels of TNF.  41% of people with one An allele had IBS vs 26% of the people that didn’t. (R)
TRANSIT:
A mutation in the FGF4 gene (rs351855 – TT) results in slower gut transit. (R)
BILE:
A gene variation of TGR5 (rs11554825), a bile acid receptor, was associated with a quicker gut flow. The TC/CC group had an average 50% faster gut flow compared with the TT subgroup. (R)
OXIDATIVE STRESS:
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)

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