The exact causes of irritable bowel syndrome (IBS) remain unclear as it can have different causes and manifestations. Today, it is assumed that various causes are responsible for irritable bowel symptoms. Among other things, the following are considered causes of IBS, although these can also overlap and influence one another:
- Diarrhea and infections (post-infectious IBS)
- Imbalance in the intestinal flora (microbiome) and bacterial overgrowth
- Micro-inflammation with accumulation and overactivity of immune cells in the intestinal wall (e.g. mast cells, enterochromaffin cells and T cells)
- Disorder of the intestinal barrier and increased permeability to the mucous membrane (permeability)
- Gut-brain disorder (Enteric Nervous System)
- Disruption of the autonomic nervous system and the gut-brain axis
- Disorders of bowel muscle activity (motility)
- Intestinal hypersensitivity (visceral hypersensitivity)
- Improper nutrition, food intolerance (e.g. fructose or lactose intolerance) and carbohydrate malabsorption
- Environmental factors (e.g. environmental toxins)
- Psychosocial issues
- Genetic predisposition
How does post-infectious IBS develop?
Almost every person suffers from a gastrointestinal infection (infectious gastroenteritis) in the course of their life, which leads to diarrhea. This diarrhea can be caused by Salmonella, Campylobacter, EHEC and Lamblien infections, for example. In approximately every second to third irritable bowel patient, this gastrointestinal infection is considered to be the cause of the IBS. This is called post-infectious IBS. For example, we know that around 20 percent of those infected developed IBS after the 2011 EHEC (a dangerous diarrheal disease) epidemic.
What role do infections and a disturbed intestinal flora play in IBS?
In post-infectious IBS, it is believed that even after the infection has healed, small inflammations remain in the intestinal wall (micro-inflammations). It is also suspected that the intestinal flora (microbiome) changes for a long period due to an infection. The relationship between the bacteria species firmicutes and bacteroides probably plays a role, here.
It has also been found that irritable bowel patients have more proteobacteria and firmicutes, but fewer bifidobacteria, acinetobacter, and bacteroides. A changed intestinal flora could play a role in intestinal hypersensitivity (hypersensitivity), inflammation in the intestinal wall and other irritable bowel symptoms. After an infection of the intestine, the risk of developing IBS is about seven times as high. In those affected by post-infectious IBS, diarrhea is usually the main symptom.
What role does a disturbed intestinal barrier play?
The intestinal wall is covered with a mucous membrane. Similar to our outer skin on the body, the inner mucous membrane on the intestine also forms a barrier to non-endogenous and harmful substances. This is how the intestinal mucosa separates our body from the food and other substances. An intact intestinal flora (microbiome) is of crucial importance for maintaining the barrier. It has been found that in irritable bowel patients the intestinal wall shows not only micro-inflammations but also permeability. One speaks here of a disturbed intestinal barrier or leaky gut syndrome.
The reduced resistance of the intestinal wall in IBS can be explained, among other things, by a reduction in the tight junctions between the cells of the intestinal wall. The tight junction proteins ZO-1 and occludin probably play a special role here. If the intestinal barrier is disturbed, foreign substances and bacteria can penetrate the intestinal wall more easily. This can promote inflammation and immune reactions, which has a negative impact on pain sensitivity, for example.
The causes of the increased permeability of the intestinal wall include:
- Nutrition (possibly gluten, wheat ATIs, FODMAPs)
- Psychosocial stress
- Disturbed bile metabolism and bile acid loss syndrome (possibly genetic disposition, Beta-Klotho (KLB) -SNP)
- Bile acid, fat, or carbohydrate malabsorption
- Disorders of the hormone and immune system (possibly genetic predisposition to immune activation by Toll-like receptor 9 and tumor necrosis factor superfamily 15)
- Disturbances in the intestinal flora (dysbiosis)
It is difficult to distinguish between causes and consequences because the individual factors influence each other.
Is the risk of mental illness increased due to post-infectious IBS?
Even if the initial cause of post-infectious IBS is on a purely physical level, this type of IBS often leads to mental illness in the long term. At the same time, this psychological component can promote the maintenance of subjective intestinal symptoms, although no physical cause for the IBS can be found (somatization). The risk of somatization depends, among other things, on the severity of the intestinal infection and the individual's psychosocial background. The risk can be increased, for example, if there was previously an anxiety disorder, depression or great stress.
A certain connection between nerves and hormones is crucial in the interactions between the intestinal flora, intestine and psyche. This is also called the **microbiome-gut-brain **axis and is important for understanding the connections between body and psyche in IBS. This connection is the subject of current research. It is known that the concentration of the hormone serotonin changes in irritable bowel patients. Serotonin also plays an important role in depression. In irritable bowel patients with diarrhea as the main symptom (type D), the serotonin level rises frequently, and in those with constipation it tends to decrease.
What is the cause of visceral hypersensitivity with IBS?
**Visceral hypersensitivity **refers to a general hypersensitivity of the intestine and other abdominal organs to pain. Doctors also speak of a reduction in the pain threshold. In IBS, stimuli that are not perceived by healthy people or are not very disturbing are rated as painful.
Hypersensitivity in IBS was found in complex experiments in which the pressure on the intestinal wall was gradually increased. Increasing pressure or certain irritating substances in the intestine lead more quickly to abdominal pain and a feeling of fullness in irritable bowel patients. To date, it is still not known how this increased sensitivity occurs. Basically, the causes can lie at the level of the intestine, spinal cord or brain. However, visceral hypersensitivity is probably a combination of different causes. The messenger substances TNF-Alpha and TRPA1 also play an important role.
In post-infectious IBS, it is assumed that the nerves ending in the intestinal wall, which are important for pain transmission, are irritated by the inflammation. After the infection has subsided, the activation of the pain-guiding nerves can persist, as a result of which the nerves do not return to their original resting state. This results in hypersensitivity.
What influence does intestinal motility have?
The muscle activity of the intestine is called motility. It is responsible for the transport of food through the intestine. For a healthy motility a complex interaction between the nervous system of the intestine, the brain and the intestinal muscles is necessary. Through targeted tensioning and relaxation of certain sections of the intestine, similar to a toothpaste tube, the food pulp is moved through the intestine.
It has been shown that the transport of food through the intestine is disturbed in IBS. With the diarrhea type (IBS-D) the transport time is reduced and with the constipation type (IBS-O) it is reduced. This is due to a correspondingly increased (IBS-D) or reduced (IBS-O) motility. The extent to which motility disorders are a cause or a consequence of IBS is still unclear. Today we know that the hormone serotonin also plays an important role in motility disorders.
Is IBS inheritable?
It is suspected that IBS may be inheritable. The detection of an hereditary component is not so easy and usually works best through so-called twin studies. Twins are almost identical genetically. Twin studies are therefore examining how certain diseases such as IBS develop in twins who grow up in different families. It was found that the risk of developing IBS is slightly increased in twins, even if they grow up in different locations. Since the twins have different social, psychological and environmental stress factors due to the different families, this is an indication of the inheritance of IBS.
There are currently indications that genes that are important for the tolerance of certain foods or intestinal activity (motility) could be changed in IBS. However, there is no single gene that can trigger and pass on IBS. Rather, it is different genes that favor the development of IBS in conjunction with environmental factors.
Some genes associated with IBS are:
- Mitochondriale DNA
- Serotonin transporter (SERT)
- Serotonin receptor 2a and 3
- Sodium channel (Nav1.5 on pain fibers)
- Fatty Acid-hydroxylase,
- Alpha-2 adrenoceptor
- TNF Alpha
Which environmental factors favor IBS?
IBS is more common in some families. This can be explained either by the genes or by a certain environmental impact in the family.
Some diseases are favored by low birth weight in newborns. This is attributed to the diet of the fetus during development. Such a connection could also be proven with IBS.
In addition, other environmental influences are also discussed as causes of IBS. Possible beneficial factors include, for example
- Psychosocial stress
- Industrially processed iron
- Medications (e.g. antibiotics)
- Excessive hygiene
- Environmental pollution
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