Irritable bowel syndrome (IBS)


A group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habit, and with features of disordered defecation.

Abnormalities may be mediated by CNS and enteric nervous system function alterations.

Associated with altered bowel sensitivity and motility.

About 10 to 15% of adults have symptoms of IBS.

Patients with IBS present with four main symptoms: abdominal discomfort or pain, diarrhea, constipation, and bloating.

Patient may have other functional gastrointestinal disorder symptoms including postprandial upper abdominal discomfort, fullness, nausea, uncommonly vomiting, and heartburn.

Annual direct costs associated with IBS estimated at more than $1 billion in the US.

Most common functional gastrointestinal disorder manifested as abdominal pain and discomfort and altered bowel function.

Commonly attributed to disorders of gut-brain interactions: resulting in visceral hypersensitivity and peripheral mechanisms initiating perturbations of gastrointestinal motor and sensory functions.

In the past, functional bowel disorders such as irritable bowel syndrome that produced symptoms of bloating were attributed to increased production of intestinal gas.

In normal subjects, even very high rates of gas infusion into the small intestine (30 ml/min) are tolerated without complaints of pain or bloating and harmlessly passed as flatus per rectum.

Studies aiming to quantify the total volume of gas produced by patients with irritable bowel syndrome have consistently failed to demonstrate increased volumes compared to healthy subjects.

The proportion of hydrogen produced may be increased in some patients with irritable bowel syndrome, but this does not affect the total volume.

The volume of flatus produced by patients irritable bowel syndrome who have pain and abdominal distension would be tolerated in normal subjects without any complaints of pain.

Symptoms are result of: abnormal colonic transit, abnormal rectal evacuation, intestinal Irritants such as maldigested carbohydrates, or fats, excess of bile acids, gluten intolerance, altered microbiome, entero-endocrine cell products, and genetic susceptibility to altered bile acid synthesis and inflammation.

Luminal and mucosal irritants can alter the mucosal permeability and activate immune or inflammatory processes which alter local reflex and activate local reflexes altering motility and intestinal secretions.

Pain or discomfort for 12 weeks of the previous 12 months associated with pain relief with defecation, looser or more frequent stools, hard or less frequent stools, passage of mucus, bloating or feeling of abnormal distension.

Intraluminal and mucosal irritants can also stimulate visceral hypersensitivity and pain.

Over the long term symptoms remain unchanged in 50% of patients, worse in approximately 20%, and improve in30% of patients with IBS.

Symptoms may change over time, most frequently from constipation or diarrhea predominant IBS mixed type or vice versa.

In post infectious IBS prognosis is better and symptoms resolve in approximately 50% of patients after 6 to 8 years.

Postinfectious IBS occurs after the infection results in 4 to 40% of patients with infectious gastroenteritis.

One in 6 persons in the United States has acute infectious gastroenteritis every year.

Postinfectious IBS probably accounts for a substantial proportion of new cases of IBS.

Postinfectious IBS is more likely to occur after severe and prolonged gastroenteritis in women older than 60 years, and smokers, any patients with anxiety, depression, hypochondriasis, or an adverse life event in the preceding three months.

Compared with men, women more often seek healthcare services including care for IBS and other functional bowel disorders by a ratio of 2-2.5 to 1.

Diagnosis rests on the symptomatology of recurrent abdominal pain or discomfort for at least three days per month in the previous three months and associated with: improvement with defecation, onset of a change in the frequency of bowel movements, or onset associated with change in stool appearance.

All patients with suspected IBS should undergo a complete blood count. colorectal cancer screening as dictated by age and associated risk factors.

In patients with diarrhea, testing for celiac disease as well as colonoscopy with random biopsies should be considered.

In the evaluation of patients with suspected IBS obtaining sero-or stool inflammatory marker measurements such a C-reactive protein or fecal calprotectinin may be part of the initial evaluation.

Testing for fecal calprotectin or lactoferrin are indicated to rule out inflammatory bowel disease in patients with  non bloody diarrhea.

Testing for bile acid diarrhea  in patients with IBS is considered, since about 25% of patients with IBS-D or functional diarrhea have bile acid diarrhea

CDtb and anti-vinculin antibodies are linked to IBS with the 91.6% certainty (Pimental M et al).

IBSchek test is a ELISA test for serum biomarkers anti-CdtB and anti-vinculin.Specific bacteria such as Campylobacter jejuni,E coli, and some species of Salmonella and Shigella can generate a toxin CdtB to which the bodycreates antibodies.

The above antibodies cross-react to vinculin, a protein in the lining of the gastrointestinal tract, resulting in an autoimmune response that adversely affects the function of the gut, leading to neuronal degradation and reduced motility.

Reduced motility placed the small intestine bacterial overgrowth,causing bloating and abdominal pain seen in IBS.

Pathophysiologic abnormalities are intrinsic to smooth musclethe gut, visceral hypersensitivity and CNS hypervigilance.

More frequent in women, although symptom severity, illness effect, and psychological distress seem similar in men and women. Among patients with IBS, women are more likely to have severe symptoms and coexistent anxiety or depression.

Constipation or bloating and diarrhea are more common in women and men, respectively, perhaps partly because defecatory disorders, which cause constipation, are more common in women. 

Symptoms may include abdominal pain, bloating, changes in bowel habits, constipation with fewer than 3 bowel movements per week, hard or lumpy stools, and straining during bowel movements.

As many as 20% of Americans may experience signs of irritable bowel syndrome, with approximately one-third of those affected experiencing constipation often accompanied by abdominal pain, affecting as many as 10 million Americans.

Abdominal distension peaks 4-6 hours before bedtime and is correlated with bloating in patients with constipation predominant irritable bowel syndrome.

Treatment indicated when symptoms diminish the patients quality of life.

With constipation alone may change to constipation and diarrhea and other functional gastrointestinal symptoms over time.

Natural history associated with a chronic relapsing and remitting course of disease.

There is a greater 24 hour fluctuation in abdominal girth in patients with IBS compared to healthy control patients.

Equally divided between diarrhea, constipation and alternating between diarrhea and constipation forms.

Approximately one third of patients experience constipation during episodes of disease process.

Patients have delayed transit time of gas along the gut and increased gas retention compared to controls, with gas retention in the jejunum being the main cause of symptoms.

Studies have shown that the total amount of gas in the bowel of symptomatic patients with IBS is the same as in asymptomatic controls indicting that the major mechanism for bloating is the abnormal perception of intestinal gas.

2:1 female predominance.

The first presentation is usually between 30 and 50 years of age.

Incidence is 10% in the U.S.

Prevalence of 1-20% worldwide

Prevalence estimated to be 11.8% in North America.

75% of affected patients never seek care for IBS.

Prevalence in North America 5-10% and affects any age group.

$1.6 billion in direct medical costs and $19 billion in the indirect costs annually.

Approximately 30 million people in the U.S. meet the criteria for diagnosis.

Prevalence 3-22% depending on criteria used for the diagnosis.

14-24% of women and 5-19% of men in the U.S. have syndrome.

May occur at any age, however most adults or 25-54 years of age.

Is estimated that about 60% of patients with IBS – diarrhea originates from some form of gastroenteritis.

IBS – diarrhea is considered to be a microbiome disease.

Incidence lower in Hispanics than in whites, but similar betweenAfrican Americans and whites.

Most prevalent digestive disease representing 12% of visits to primary care physicians and 40% of referrals to gastroenterologists.

No biological marker explains the findings in IBS.

Alteration in intestinal microbiota is speculated.

No structural marker is present.

Long term prognosis is good and in a few individuals, symptoms can resolve.

Only 30% of patients seek medical attention for this process. ROME II criteria for diagnosis: at least 12 weeks (which need not

be consecutive) in the preceding 12 months of abdominal pain ordiscomfort that has 2 of the following features, relief with defecation, onset associated with a change in stool frequency or onset associated with a change in form or appearance of stool.

Rome III diagnostic criteria for IBS requires the presence of recurrence of abdominal pain or discomfort for at least three days per month during the last three months with onset of more than six months prior.

Rome III criteria stratify IBS subtypes based in the predominant bowel symptoms:

IBS with constipation, IBS-C, IBS with diarrhea IBS-D, mixed type IBS IBS-M and unclassified IBS, IBS-U.

Rome definition of IBS: recurrent abdominal pain, on average, at least one day per week for the last three months and then associated with two or more of the following criteria: related to defecation, associated with the change in frequency of stool, associated with a change in form of stool, and the criteria fulfilled for the last three months with a symptom onset 6 or greater months before diagnosis.

Supporting symptoms not required for diagnosis but helpful in confirmation include a abnormal stool frequency less than three bowel movements per week or greater than three bowel movements per day, be abnormal stool form, defecation straining, urgency to stool, passage of mucus and bloating.

Diagnostic sensitivity associated with typical symptoms varies between 42% and 94% and the specificity varies between 55% and 94%.

Symptoms may be chronic or episodic.

The altered bowel function categorized as diarrhea predominant,constipation predominant, or mixed.

Patients with increased risk for fibromyalgia and interstitial cystitis.

Fibromyalgia affects 26% to 65% of patients with IBS.

Patients miss three times as many days of work per year than persons without irritable bowel syndrome and restrict their activities on average of 145 days per year.6-16% of adolescents.

Patients undergo appendectomies, cholecystectomies and hysterectomies at higher rates than the general population.

The ileum, colon and rectum of patients with IBS have exaggerated responses to provocative stimuli.

Patients with IBS have enhanced perception of visceral events.

Abdominal pain is highly variable with 25% having hypogastric pain, 20% right-sided pain, 20% left-sided pain and 10% with epigastric pain.

Treatment strategies include dietary, psychotherapy, pharmacotherapy, and microbial therapies.

Dietary approaches for IBS symptoms have mixed results.

Dietary fiber results has been minimal to no improvement, and may be associated with aggravation of symptoms for some patients.

Gluten withdrawal does not significantly improve IBS symptoms in controlled studies.

A low FODMAP diet is recommended for symptom control.

Metaanalysis however show no significant benefit of a low FODMAP diet, and benefits that appear are probably due to the placebo effect.

Treatment of constipation with IBS includes bulking agents, osmotic laxatives, tegaserod, 5-HT4 partial agonist and lubiprostone.

Overall psychological therapies are not effective in relieving symptoms.

Antibiotic treatment in IBS correlates with normalization of results of lactulose hydrogen breath tests.

The mainstays of treatment or anti-spasmodic and neuromodulator agents for pain, and loperamide and serotonin type 3 antagonists are indicated for women with severe IBS-D lasting six greater than six months and for whom conventional therapy was inadequate.

To treat constipation: osmotic laxatives chloride secretilogues, ion channel blocker blockers, ileal bile acid transported inhibition and prokinetic agents.

Rifaximin (Xifaxan) is an oral, nonsystemic, broad-spectrum antibiotic targets the gastrointestinal tract and is associated with low risk of bacterial resistance: in double blind trials (TARGET 1 and TARGET 2) treating patients with IBS without constipation for 2 weeks with rifaximin provided relief of symptoms, bloating, abdominal pain, and loose or watery stools (Pimentel M et al).

Treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with rifaximin is associated with significant symptomatic improvements.

Rifaximin targets the gut and can be taken orally 3 times a day for 14 days, and in those who have a recurrence they can be retreated with another 14-day course up to two times.

In the TARGET 3 study that included 2,579 patients, 42% of patients responded to 2 weeks of treatment with of at least a 30% reduction in pain and a 50% or greater decrease in the number of days with scores or 6 (loose) or 7 (watery) on the Bristol Stool Scale.

In the above study 36% of initial responders never relapsed over 18 to 22 weeks of follow-up.

Of the 64% who did relapse that were randomized to a second blinded 2-week course of treatment or placebo, 33% on rifaximin again responded compared with 25% of those receiving placebo.

Of those who again relapsed were re-randomized to the active treatment or placebo, and 37% of the rifaximin group responded compared with 29% of the placebo group.

Study suggested patients with IBS retreated with Rifaximin continue to have benefit.

As a result of above study, it is now believed that a substantial number of patients with IBS have increased microbes in the small intestine.

In the TARGET-3 study the administration of rifaximin, 550 mg three times daily for 2 weeks, followed by a 4-week treatment-free phase during which efficacy was assessed.

In TARGET 3! those who underwent retreatment after symptoms recurred were mostly women, whose mean age was 47.

In the above study gene sequencing and cultures with antibiotic susceptibility testing showed that three courses of treatment led to no changes in bacterial sensitivity and no cross-resistance to other agents.

After only 10 days of treatment with systemic antibiotics, the gut microbiota can be altered for up to 1 year.

A single and the repeat 2-week courses of nonsystemic rifaximin had minimal effects on the gut microbiota of patients with IBS-D.Eluxadoline (Viberzi) is approved for IBS -D.

Eluxadoline activates receptors in the nervous system that may reduce bowel contractions.

IBS patients can identify the foods that trigger their symptoms.

Perceived food intolerance is a common problem with significant nutritional consequences in a population with IBS. 

70% of IBS patients have symptoms related to intake of food, and 62% limited or excluded food items from the diet. 

Data for the use of a gluten-free diet in IBS is still evolving.

Data for lactose restriction is insufficient data to support the use of this in IBS.

The role of fiber in IBS has demonstrated mixed results.

Linaclotide indicated for IBS syndrome with constipation .

A chronic functional gastrointestinal disorder that affects between 10 and 20 percent of the population.

It is a disorder of the brain-gut axis, IBS is divided into subtypes according to the predominant stool pattern and has several associated pathophysiological mechanisms.

The current approach to IBS remains focused on treating the patient’s predominant or most troublesome symptoms.

About 75% of people with IBS can benefit from a low-FODMAP diet.

Most pharmacotherapies have a modest impact and lack high-quality evidence supporting their efficacy.

No pharmacologic therapy have been shown to alter the disease mechanisms leading to gut dysfunction, or the long-term natural history of the disorder.

Antispasmodics inhibit the action of acetylcholine at muscarinic receptors, or by blocking calcium channels on gastrointestinal smooth muscle.

Treatment options include hyoscyamine and dicyclomine for abdominal pain.

Peppermint oil has antispasmodic properties, inhibiting smooth muscle contractility in the GI tract by blocking calcium influx.

Antidepressants affect GI motility and sensation, in addition to their central effects.

Tricyclic antidepressants prolong orocecal and whole-gut transit times, and selective serotonin reuptake inhibitors decrease orocecal transit time.

TCAs are recommended for the treatment of IBS-D, and SSRIs for the treatment of IBS-C.

Anti-diarrheal agents loperamide and diphenoxylate are �-opioid receptor agonists.

Eluxadoline is an approved novel mu opioid receptor agonist and ?-opioid receptor antagonist with efficacy in treating IBS-D.

Management includes developing relaxation techniques and engaging in exercise.

Randomized clinical trials suggest vigorous physical activity is associated to reduction in IBS and psychological symptoms. 

Yoga is reported to reduce severity of IBS and somatic symptoms and walking improves overall G.I. symptoms, negative affect, and anxiety.

First line pharmacological agents include spasmolytic or anti-spasmodic agents, such as sublingual hyoscyamine for pain, loperamide for diarrhea or mixed bowel dysfunction, and dietary fiber, 20 g per day,  and osmotic laxative for constipation.

Patients with a history of biliary obstruction, cholecystectomy, pancreatitis, severe liver impairment or severe constipation, and patients who consume more than three alcoholic drinks per day, should not be prescribed eluxadoline.

Drugs that act on the 5-HT3 receptor can retard colonic transit and reduce visceral pain through effects on the brain, visceral afferents and the enteric nervous system, and includes alosetron for severe IBS-D in female patients.

GABAergic agents including gabapentin and pregabalin, reduce the release of several excitatory neurotransmitters involved in pain mechanisms, and may relieve pain and other symptoms in patients with IBS.

Approximately 25 percent of patients with IBS-D show evidence of bile acid malabsorption.

Studies suggest that rifaximin can improve IBS symptoms and relieve bloating, possibly by treating small intestinal bacterial overgrowth, or by accelerating colonic transit.

Chloride channel-related agents, such as lubiprostone, linaclotide and plecanatide, and sodium-hydrogen exchangers, such as tenapanor may be beneficial?

5-HT4 receptor agonists include tegaserod, prucalopride, naronapride, velusetrag and mosapride may be beneficial.

Fecal microbiota transplant is not effective in IBS.

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