Observed genes

Polygenic score

Influential genes: NCAM1, CADM2

Studies have shown that alterations in NCAM1 expression or function may be associated with changes in gut motility and visceral sensitivity, which are key features of IBS.

Recent studies have found an association between CADM2 gene variants and IBS.

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Overview

Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract characterized by otherwise unexplainable abdominal pain and a change in bowel movements. Its pathophysiology is not entirely understood, although multiple factors have been shown to influence the occurrence of symptoms:

• genetics
• gut microbiome composition
• gastrointestinal infections
• psychological factors such as anxiety and stress
• food intolerances

Generally, it is believed to be caused by increased sensitivity and exaggerated responsivity of the intestines.

Prevalence & Risk factors

IBS is among the most common chronic illnesses, with an estimated 10-20% of the population experiencing some symptoms. [4] Prevalence is higher in women than men and increased in people under 50 years of age. Women aged 20-40 are most affected by IBS. [2] There are few established risk factors for the development of irritable bowel syndrome. Various functional somatic syndromes (e.g., fibromyalgia) are associated with a higher prevalence of IBS. A previous acute infection of the intestines is observed in ~10% of the patients. In patients with such post-infectious IBS, the prognosis may be slightly better.

Genetics (by Barbora Hamerníková)

IBS is a multifactorial, stress-sensitive disorder, in which family clustering has been observed. Close relatives are 2-3x more likely to develop the disease. [5] However, no major genetic factors contributing to the development  of IBS are known. [6] Genetic, as well as environmental and psychological factors (“brain-gut-axis” dysfunction), together increase the risk of IBS.

The research is still ongoing, often in connection to single nucleotide polymorphisms (SNPs – change of a single nucleotide in the DNA strand), but the findings vary. SNPs in genes alone may not be enough to cause IBS, but they can interact with other genes or environmental factors and lead to disease development. [5]

Some studies noted that a defect in the SCN5A gene was found in about 2.2 % of IBS patients, and furthermore confirmed by a genome-wide association study (GWAS). [7]

It has been observed that rs4263839 and rs6478108 variants (in the gene TNFSF15) are associated with a higher risk of IBS. Genetic analysis also demonstrated that the TNFSF15 gene is a race-specific susceptibility gene for IBD. [8]

It is proven that the effects of long-term stress may result in epigenetic changes as well (they modify the gene expression without changing the DNA sequence and cause alterations in phenotype). [6]

In Macromo, we use polygenic risk scores (PRS) to determine genetic risk, as a disease is not caused by a single gene. The PRS is an estimate of the probability that an individual carries a given trait based on genetics, without considering environmental factors. Variants across their genome are summed and weighted according to their effect on the disease or trait. [9]

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Signs & Symptoms

The defining features of IBS include abdominal pain and a change in stool consistency or frequency. The pain is usually crampy and can vary in intensity. There are multiple subgroups of IBS based on the predominant stool pattern:

• IBS with diarrhea
• IBS with constipation
• IBS with mixed stool pattern
• IBS unclassified

About 50% of patients with IBS have a mucous discharge in diarrhea. Nocturnal loose stools are very uncommon in IBS. On the other hand, constipation in IBS can be irregular and last for days. Other common features of IBS include excessive gas, belching, and a bloating sensation.

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Diagnosis

Diagnosis of IBS can be difficult due to its non-specific symptoms. There is no established biomarker or one standard test for IBS diagnosis. Diagnosis is made based on clinical symptoms, medical history, and physical examination. A colonoscopy can help exclude other causes of symptoms.

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Therapy

The goal of IBS therapy is to manage its symptoms. Due to its complicated and not well-understood pathophysiology, treatment may take a long time before finding the most helpful path. Dietary changes can be beneficial, such as excluding foods that have been identified to aggravate symptoms of IBS or increasing dietary fiber. Furthermore, personalized psychosocial treatment aimed at decreasing stress and anxiety may help. Lastly, many medications can help manage the symptoms, such as anticholinergic medications (medications that block the action of acetylcholine), anti-anxiety drugs, and others. However, pharmacologic therapy is usually only indicated when dietary changes have not helped sufficiently. It is also important to remember that these drugs do not cure the condition; they merely aid with the symptoms.‍

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Prevention

It is important to consume a varied diet with an adequate intake of micronutrients and dietary fiber. Nevertheless, there is no definitive preventive measure for IBS.

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Prognosis

Most people with IBS lead a normal life while controlling their symptoms without serious health problems. It is essential to monitor the symptoms to identify better the potential specific triggers of pain or bowel habit changes.

Recommendations

• If you experience abdominal pain, diarrhea, or constipation regularly, monitor your symptoms over time. Keeping track can help your clinician identify your triggering or exacerbating factors.
• Improve your health by eating a varied diet including adequate amounts of fiber.

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