Irritable bowel syndrome

• 1. Introduction

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  No blood test, scan or biopsy can confirm irritable bowel syndrome, or IBS, a condition that shapes daily life for a great many people. Worldwide, the average prevalence is 11.2%. Doctors call it a functional gastrointestinal disorder, meaning it is recognized by its pattern of symptoms. Those symptoms usually include abdominal pain, bloating and changes in the consistency of bowel movements. They can last for years and may cause missed school or work, or reduced productivity on the job. Even so, IBS does not affect life expectancy or lead to other serious diseases. Why does a disorder this common stay so hard to pin down? What do physicians look for, and what must they rule out first? And why do remedies range from carefully planned diets to low-dose antidepressants and peppermint oil?

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• 2. The Symptom Pattern

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  An IBS attack usually subsides within one day, but recurrent attacks are likely. The central symptom is abdominal pain or discomfort, tied to frequent diarrhea or constipation and a change in bowel habits. Some people also feel urgency, bloating, or a sense of incomplete evacuation called tenesmus. In some cases a bowel movement brings relief. Under the Rome IV diagnostic criteria, symptoms count as chronic once they have been present for at least 6 months.

  Four main labels describe how the condition behaves. IBS-D is diarrhea-predominant and IBS-C is constipation-predominant. IBS-M, also written IBS-A, describes a mixed or alternating stool pattern, and a fourth group is pain-predominant. Some cases begin suddenly after an infectious illness marked by two or more of fever, vomiting, diarrhea or a positive stool culture. That form is called post-infectious IBS, or IBS-PI.

  A study of 97,593 people with IBS found headache, fibromyalgia and depression among its common companions. IBS occurs in 51% of people with chronic fatigue syndrome and 49% of people with fibromyalgia. Psychiatric disorders occur in 94% of people with IBS. Gastroesophageal reflux, backache, sleep disorders and anxiety also turn up more often than in other people. About a third of adults with IBS report sexual dysfunction, typically a reduction in libido.

  Some people with IBS and constipation also have pelvic floor dysfunction. It may mean needing to manually disimpact stool, or bladder symptoms such as nocturia, which is urination at night, and frequent urinary tract infections. One study reported a statistically significant link between migraine headaches, IBS and endometriosis. Genetic channelopathies, which cause cardiac conduction defects and neuromuscular dysfunction, also come with IBS, as do the myotonic muscular dystrophies. In those dystrophies, digestive symptoms may appear up to 10 years before the muscle features.

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• 3. Stress And Signals

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  Since the 1990s, researchers have suggested that the brain-gut axis plays a role in IBS. Childhood physical and psychological abuse is often associated with developing the condition. Psychological stress is believed to trigger it in predisposed people. The hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, the body's two main stress responders, have both been shown to operate abnormally in people with IBS. Psychiatric illness or anxiety precedes IBS symptoms in two-thirds of those affected. Many also report trouble falling asleep and frequent waking during the night.

  Serotonin, also written 5-hydroxytryptamine or 5-HT, offers a chemical clue. Abnormal 5-HT metabolism and a high density of nerve fibers in the intestinal lining have both been implicated. Several receptor subtypes are involved, including 5-HT3, 5-HT4 and 5-HT7. High levels of nerve fibers carrying the 5-HT7 receptor were observed in the colon of people with IBS. In mouse models with visceral hypersensitivity, a novel 5-HT7 antagonist given by mouth reduced intestinal pain.

  People younger than 50, women, and those with a family history are more likely to develop IBS. The condition has been reported more often in multigenerational families than in the general population. SCN5A mutations are found in a small number of people with IBS, particularly the constipation-predominant type. The defect disrupts the Nav1.5 channel in smooth muscle of the colon and in pacemaker cells. A lack of physical activity is associated with a higher prevalence, and IBS is more prevalent in obese patients. Vitamin D deficiency is also more common in people with IBS, and the vitamin helps regulate the gut microbiome, inflammation and immune responses.

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• 4. Infection And Microbes

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  Roughly 10 percent of IBS cases are triggered by an acute gastroenteritis infection. After such an infection, the risk of developing IBS rises six-fold, and a prolonged fever during the illness raises it further. Antibiotic use also appears to increase the risk. Post-infectious IBS usually shows up as the diarrhea-predominant subtype.

  The CdtB toxin, produced by bacteria that cause gastroenteritis, may set off an autoimmune response. Host antibodies to CdtB cross-react with a protein called vinculin. Separately, high levels of proinflammatory cytokines during acute infection increase gut permeability. That lets resident gut bacteria cross the epithelial barrier, which can damage local tissue and become a chronic abnormality in sensitive people. Increased permeability is strongly associated with IBS whether or not an infection started it.

  Small intestinal bacterial overgrowth, or SIBO, occurs more often in people with IBS than in healthy controls. It is most common in IBS-D but also appears more frequently in IBS-C. Broader shifts in gut flora, called dysbiosis, are associated with the intestinal symptoms of IBS. They are also associated with the psychiatric illness that coexists in up to 80% of people with IBS.

  Bacillota is the most common phylum of gut bacteria. It includes Lactobacillus, which decreases in people with IBS, and Streptococcus, which increases. Within the class Clostridia, Ruminococcus and Dorea are more abundant. In IBS-D, the family Enterobacteriaceae rises. Many patients show reduced overall microbial diversity, and antibodies against flagellin, a component of common gut bacteria, are a frequent finding.

  Chronic low-grade inflammation is common in IBS, with increased enterochromaffin cells, intraepithelial lymphocytes and mast cells in the gut lining. In one set of studies, a considerable portion of patients showed immediate mucosal responses to certain foods during confocal endoscopy. More than 70% of those patients gained significant symptom relief after customized dietary restrictions. Blastocystis and Dientamoeba fragilis colonisation also occurs more commonly in people with IBS, though their role in the condition is unclear.

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• 5. Diagnosis By Elimination

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  The Rome criteria let a diagnosis rest on symptoms alone. The Rome IV version asks for recurrent abdominal pain, on average at least one day a week in the last three months, plus stool- or defecation-related criteria. Yet no criteria based solely on symptoms are accurate enough to diagnose IBS. Physicians are advised to minimize the use of medical investigations.

  Alarm features, also called red flags, push doctors to look further. They include onset after age 50, weight loss, blood in the stool, iron-deficiency anemia, or a family history of colon cancer, celiac disease or inflammatory bowel disease. Red flags are imperfect guides, though. As many as 31% of people with IBS have blood in their stool, many possibly from hemorrhoidal bleeding.

  Five kinds of investigation make up the usual exclusion list. Stool microscopy and culture rule out infection. Blood tests include a full blood examination, liver function tests, erythrocyte sedimentation rate and serology for coeliac disease. Abdominal ultrasound checks for gallstones, and endoscopy with biopsies looks for ulcers, coeliac disease, inflammatory bowel disease and malignancy. Hydrogen breath testing detects fructose and lactose malabsorption.

  Colon cancer, thyroid disorders and giardiasis can all produce abnormal defecation and abdominal pain. Rarer causes include carcinoid syndrome, microscopic colitis and eosinophilic gastroenteritis. Testing for those yields few positive results, so it is considered difficult to justify the expense.

  People with IBS are 87% more likely to undergo abdominal and pelvic surgery. They are three times more likely to have gallbladder surgery and twice as likely to have a hysterectomy. The cause is not a higher risk of gallstones. It is abdominal pain, awareness of having gallstones and inappropriate surgical indications.

  The American College of Gastroenterology recommends that everyone with IBS symptoms be tested for coeliac disease. Some people managed for years for IBS may instead have non-celiac gluten sensitivity, whose digestive symptoms are clinically indistinguishable. Non-intestinal signs such as headache, chronic fatigue, joint pain or skin rash can hint at it. Bile acid malabsorption is also sometimes missed. SeHCAT tests suggest around 30% of people with diarrhea-predominant IBS have it, and most respond to bile acid sequestrants.

  A three-year study found that patients diagnosed with IBS were 16.3 times more likely to be diagnosed with inflammatory bowel disease during the study period. The likely explanation is an initial misdiagnosis.

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• 6. Diet And Movement

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  A low-FODMAP diet restricts fermentable oligosaccharides, disaccharides, monosaccharides and polyols. There is evidence that, when supervised by a dietitian, it is the best-studied diet for controlling IBS symptoms, though evidence on possible adverse effects is lacking. The National Institute for Health and Care Excellence, known as NICE, recommends it when symptoms persist despite general dietary and lifestyle changes. NICE says it must be run by a healthcare professional with dietary training and should not be the only approach.

  Gluten complicates the picture. A low-FODMAP diet also reduces gluten, so improvement may come from dropping gluten rather than FODMAPs. That can hide unrecognized celiac disease, delaying correct treatment and risking several serious complications, including various types of cancer.

  Soluble fiber such as psyllium, also called ispagula husk, may improve symptoms but does not appear to reduce pain. It acts as a bulking agent. For many people with IBS-D it allows a more consistent stool. In IBS-C it gives a softer, moister stool that passes more easily. Insoluble fiber such as bran is not effective and may aggravate symptoms in some people. The research contains conflicting small studies using different fiber types and doses.

  Magnesium salts such as magnesium oxide act as osmotic laxatives, drawing water into the gut and increasing stool frequency in IBS-C. Evidence for magnesium specifically remains limited, with a lack of high-quality randomized controlled trials. Its laxative effect may worsen symptoms in IBS-D.

  The latest British Society of Gastroenterology guidelines state that all patients with IBS should be advised to take regular exercise. That is a strong recommendation based on weak certainty evidence. Swimming, walking and running are among the suggested activities. Yoga may improve gastrointestinal symptoms, decrease anxiety and depression, and enhance quality of life.

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• 7. Medicines And Remedies

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  Loperamide may help with diarrhea, while laxatives may help with constipation. For people who do not respond to dietary fiber, osmotic laxatives such as polyethylene glycol, sorbitol, lactulose and erythritol can help avoid the "cathartic colon" associated with stimulant laxatives. Lubiprostone is used for constipation-predominant IBS.

  A meta-analysis by the Cochrane Collaboration concluded that one out of seven people benefit from antispasmodics such as hyoscyamine or dicyclomine. Mebeverine belongs to the musculotropic group, which acts directly on smooth muscle to relieve spasm without affecting normal gut motility. Because that action is not mediated by the autonomic nervous system, the usual anticholinergic side effects are absent.

  Low doses of tricyclic antidepressants such as amitriptyline or nortriptyline help about one in three people. The doses are often lower than those used for depression, and they can work even without a mood disorder. Amitriptyline is believed to help not simply by altering mood, but by reducing visceral afferent firing, possibly through nerve-mast cell crosstalk. Evidence for SSRIs is weaker, and as of 2015 it indicated that they do not help.

  Drugs aimed at serotonin were once proposed, with 5-HT3 antagonists for IBS-D and 5-HT4 agonists for IBS-C. Severe side effects led the Food and Drug Administration to withdraw them. They are now prescribed under an emergency investigational drug protocol.

  Proton pump inhibitors, which suppress stomach acid, may cause SIBO and so IBS symptoms. Stopping them in selected individuals has been recommended. Rifaximin may relieve bloating and flatulence, especially where SIBO is involved, although relief of abdominal distension is delayed. Supplementation is recommended for people with IBS and low vitamin D. Psychological therapies have inconsistent evidence from studies of poor methodological quality. Preliminary research still links them to reductions in both autonomic nervous system dysregulation and gastrointestinal symptoms.

  Probiotics at 10 billion to 100 billion beneficial bacteria per day are recommended, although individual strains are not understood well enough for finer advice. Bifidobacteria infantis and Lactobacillus plantarum have both been found effective, but one review found efficacy only for B. infantis. In a randomized, double-blind, placebo-controlled trial, Bifidobacterium lactis BI040 significantly reduced the frequency and intensity of abdominal pain. Bacillus coagulans BC300 improved the sensation of intestinal satiety.

  Peppermint oil beat placebo in a meta-analysis, at least in the short term. A comprehensive analysis of twelve randomized trials called it an effective therapy for adults. The enteric coating must not be chewed or broken, or reflux may occur from relaxation of the lower esophageal sphincter. Iberogast, a multi-herbal extract, was also superior to placebo. Acupuncture shows no benefit over placebo for symptom severity or quality of life.

  Fecal microbiota transplant is where the evidence splits. Preliminary research reported a "cure" rate between 36 percent and 60 percent, with remission of core symptoms persisting at 9 and 19 months. A separate assessment found it does not appear useful as of 2019.

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• 8. Counting The Cost

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  Reported prevalence runs from 1.1% to 45.0%, depending on the country and the criteria used. In the developed world, about 10-15% of people are believed to be affected. IBS is more common in South America and less common in Southeast Asia. One survey of 324 people in Mexico City found 35%, a rate attributed to the stress of living in a populated city. Other studies measured abdominal pain and cramping rather than IBS itself, finding 43% in Brazil and 46% in Mexico.

  In Western countries, women are around two to three times more likely to be diagnosed with IBS and four to five times more likely to seek specialty care. Women in East Asian countries are not more likely than men to have it. Symptom severity in women often fluctuates with the menstrual cycle, and estrogen withdrawal may play a role. Sexual trauma is a major risk factor, as are other forms of abuse. Because women face higher risk of sexual abuse, that may add to the difference. The condition appears to become less common with age and typically begins before 45.

  The first description of IBS dates to 1820. P. W. Brown introduced the concept of an "irritable bowel" in The Journal of the Kansas Medical Society in 1947 and again in the Rocky Mountain Medical Journal in 1950. He used it for people with diarrhea, abdominal pain and constipation but no well-recognized infective cause. Early theories blamed a psychosomatic or mental disorder. World IBS Day was founded on the 19th of April 2019 to raise awareness.

  In the United States, the aggregate cost has been estimated at $21.7-30 billion. That combines $1.7-10 billion in direct medical costs with about $20 billion in indirect costs. A managed care company study identified a 49% annual increase in medical costs associated with an IBS diagnosis. A study of workers reported a 34.6% loss in productivity, corresponding to 13.8 hours lost per 40-hour week. A 2003 Medicaid study by the University of Georgia College of Pharmacy and Novartis found added costs of $962 in California and $2191 in North Carolina. Those costs were comparable to those found for people with asthma.

  Mesalazine, also called 5-aminosalicylic acid, is an anti-inflammatory drug reported to reduce immune-mediated inflammation in the gut of people with IBS. Its use has been linked to improved symptoms, a greater feeling of general wellness and more normal gut flora. Treatment or exclusion diets based on "abnormally" high IgG antibodies cannot be recommended. A similar syndrome is found in rats, where a receptor called free fatty acid receptor 2 makes cells respond in an exaggerated way to the animal's own maldigestion products.

  Biomarker testing is not yet a reliable diagnostic tool. Still, in a study of 293 patients, human SH-Sy5Y cells exposed to serum from patients with anti-neuronal antibodies showed increased apoptosis compared with the control group.

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