Introduction:
Irritable bowel syndrome (IBS) is a stress-sensitive, complex condition with indications of familial clustering due to shared environmental or genetic causes. However, weak genetic connections have been linked to IBS, and there is no proof to conclude that significant genetic factors play a role in the condition's pathophysiology.
Studies on stress in animals, including early-life stressors, point to the involvement of environmental variables in the pathophysiology of IBS. In particular, stress is linked to dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and corticotropin-releasing factor pathways. Recent research indicates that environmental influences on peripheral and central function may be mediated by epigenetic mechanisms, which are molecular alterations unrelated to changes in the gene sequence.
What Is IBS and Its Clinical Overview?
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IBS is a prevalent condition marked by recurring abdominal discomfort or pain accompanied by bowel dysfunction like constipation, diarrhea, or both.
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Bloating, urgency, and a sense of incomplete evacuation are concurrent symptoms.
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Numerous population-based studies have revealed that between 10 % and 20 % of the general population, including children and adults of various ages, are affected. Although symptoms can appear at any age, they usually appear in the early years of adulthood.
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As general practitioners and gastroenterologists regularly see IBS, the extent of symptoms may impact a person's choice to seek medical advice. In the presence of troublesome symptoms such as fever, chills, or blood in the stool, the diagnosis of IBS is usually made without the need for lab, radiologic, or endoscopic examinations in those with classic symptoms that match Rome's criteria for the condition.
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Although gastrointestinal symptoms are widespread in the general population, little is known about the pathophysiology of IBS.
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Disordered gastrointestinal motility and interactions between the brain and the gut contribute to the symptoms in some IBS patients, and they do not account for all cases. Because the precise molecular origin of IBS is yet unknown, pharmacologic drugs from several families, chosen based on the major symptom, may be used to treat the symptoms. For example, antispasmodics should be prescribed for those who experience severe pain. Similarly, antidiarrheals may be prescribed for those who experience frequent, irritable bowels and laxatives for infrequent and hard stools.
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Selective serotonin reuptake inhibitors, anticholinergics, and GABA (gamma-aminobutyric acid) based medications are examples of pain-modulating medications. In addition to opioid-based drugs, anticholinergics, cholestyramine (a bile-salt binder), fiber, and serotonin 5-HT3 receptor antagonists may also be used as antidiarrheal treatments.
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In addition, stool softeners, fiber-based therapy, osmotic medications (based on magnesium or polyethylene glycol), serotonin 5-HT4 receptor agonists, stimulant laxatives, and substances that impact intestinal chloride ion channels can all be used to treat constipation.
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In summation, various medications with numerous underlying pharmacological mechanisms are utilized to treat the symptoms of IBS. Still, the effectiveness of these medications is based on the cause of IBS. In addition, the causes of IBS are still being investigated to develop better treatments and, ideally, shield people who are asymptomatic from developing the condition.
What Are Rome’s Diagnostic Criteria for IBS?
Rome’s diagnostic criteria for IBS is a recurrence of stomach pain once a week for three months, in addition to two or three of the following symptoms:
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Defecation.
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Change in stool frequency.
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Change in stool appearance.
What Is the Role of Mendelian Genetics in IBS?
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Classic Mendelian genetic disorders often result from a few genetic flaws in a specific gene and are passed down across families in a predictable fashion. Mendelian disorders are transmitted through pedigrees in four ways: autosomal dominant, co-dominant, recessive, or X-linked. Recent genetic research has focused on complicated genetic diseases rather than Mendelian disorders.
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A multifactorial genetic ailment with many gene mutations on several genes and influences from the environment and lifestyle is called a "complex genetic disease." These genetic impacts are minimal since the development of a disease is rarely caused solely by the existence of a specific variant. Even though they do not manifest themselves as typical Mendelian disorders do, complex gene mutations are still hereditary because they frequently cluster in families.
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Several genes have been discovered to be consistently related to Crohn's disease by family-based linkage mapping, fine-mapping research, and genome-wide correlation studies. These findings suggest successful gene discovery is achievable in other multifactorial disorders and diseases, including IBS.
What Is the Literature View on IBS and Heritability?
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Family Studies:
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Most initial research investigating family clustering of IBS has relied heavily on proxy reporting from patients who claim to have an additional afflicted family member with IBS. One study found that patient reporting of a specific relative's IBS condition could have been more accurate.
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Familial clustering exists regardless of the bowel pattern, a family member of someone with IBS is two to three times as likely to have the condition, and the recognized environmental risk factors for IBS are also prevalent in IBS families.
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Familial forms of IBS and those with "sporadic" or non-familial IBS exist. This observation raises the question of whether the sporadic or familial types of IBS share clinical traits that point to a distinct molecular basis. Genetic disorders may manifest sooner in life or in a more specialized form.
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A study discovered that subjects with a stronger family history of IBS developed symptoms of loose stools, discomfort, constipation, and pain more frequently than those with a weaker family history. They also had sequential fibromyalgia, heartburn, asthma, more severe pain, concurrent fibromyalgia, heartburn, and urgency.
2. Environmental Factors:
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Some researchers say more than 50 percent of IBS sufferers may have experienced abuse. While some research failed to distinguish childhood and adult abuse, others have found a connection between childhood trauma and irritable bowel syndrome.
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However, a subsequent population-based study discovered that, after correcting for aging, gender, and psychological variables like neuroticism, childhood abuse was not related to adult IBS.
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In contrast to the other studies, a community-based investigation indicated that people with either IBS or functional dyspepsia or maybe both were more likely to have experienced maltreatment in adulthood than in childhood.
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One study discovered a potential connection between IBS and childhood trauma. Multivariate analysis revealed no association with other maternal or perinatal variables, but abdominal suction at childbirth was linked to hospital discharge with IBS in later life. On further research on IBS outpatients, 31 percent of patients reported parental loss due to death, divorce, or separation, and 61 percent reported having a poor connection with their parents.
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The animal model for IBS has prenatally separated rat pups, which showed changed bowel habits and increased visceral sensitivity (sensitivity to physiological factors altered), just like IBS patients do. However, the fact that the twin with the lower birth weight had a higher likelihood of getting IBS and did so at a younger age implies that prenatal developmental variables may be very important to the pathogenesis of IBS. These studies imply that early childhood trauma may be a significant environmental risk factor for later developing functional gastrointestinal diseases like IBS.
Conclusion:
Although there is a good chance that people with a positive degree of relatives with IBS and individuals who seek medical care exhibit learned sickness behaviors, nine percent to 56 percent of IBS sufferers seek medical care. According to studies on familial aggregation, only 20 percent to 50 percent of people have a confirmed genetic history of IBS, and the diseased member of the family need not be a parent. In conclusion, although the parent-to-child distribution of learned sickness behavior may only be relevant to many IBS patients, the subject merits more research.
