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Disorders of Gut-Brain Interaction (DGBIs)
Overview
Disorders of gut-brain interaction (DGBIs), a group of conditions formerly known as functional gastrointestinal (GI) disorders,1-3 are associated with any combination of motility disturbances, such as visceral hypersensitivity, alterations in mucosal and immune function, gut microbiome dysbiosis, and altered central and peripheral nervous system processing.3
The update in terminology to DGBIs reflects the important role of dysfunction within the gut-brain axis in the pathophysiology of these disorders.1
An epidemiologic study published in 2021 estimated that DGBIs affect approximately 40% of the US population.3 Two of the most common DGBIs are irritable bowel syndrome (IBS), which is further categorized into subtypes (ie, diarrhea-predominant IBS [IBS-D]; constipation-predominant IBS [IBS-C]; IBS with mixed bowel habits [IBS-M]; and IBS unclassified [IBS-U]), and functional constipation, at times referred to as chronic idiopathic constipation (CIC).3-6
Irritable Bowel Syndrome (IBS)
Chronic Idiopathic Constipation (CIC)
Overview
Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction characterized by symptoms of recurrent abdominal pain and disordered defecation.9 The estimated prevalence of IBS in US adults is 4% to 5%, with rates higher among women.3,9 In the United States, new IBS cases are estimated to occur in 1% to 2% of the population annually.10
Diagnosis and common symptoms6,9
In patients with IBS, symptom onset must occur at least 6 months prior to diagnosis and be present during the past 3 months.
Abdominal pain is present at least once weekly (on average) in association with6:
- Change in stool frequency
- Change in stool form
- Relief or worsening of abdominal pain related to defecation
Bloating is a commonly reported symptom, but its presence is not necessary for diagnosis.6,9
Classification
Classification of IBS into subtypes, such as IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), is determined by the patients’ predominant bowel habit on days with abnormal bowel movements.6
Irritable bowel syndrome with diarrhea (IBS-D)
IBS-D is the most common IBS subtype.10 A positive diagnosis for IBS-D is recommended, with limited need for diagnostic testing in the absence of alarm features.6
Irritable bowel syndrome with constipation (IBS-C)
Patients with IBS-C primarily experience frequent constipation in addition to recurrent abdominal pain and bloating, which may require differential diagnosis to rule out other chronic constipation conditions.6
Additional subtypes include IBS with mixed bowel habits (IBS-M) and IBS unclassified (IBS-U).6 Patients with IBS-M report abnormal bowel habits that include both constipation and diarrhea. IBS-U includes patients who meet the diagnostic criteria for IBS but whose bowel habits cannot be categorized as one of the three other subtypes.6
Medical Unmet Need in IBS-D
*Individuals ≥18 years of age from a general US population who had experienced gastrointestinal symptoms who completed an online survey conducted September 1-15, 2014.
†Individuals who had symptoms consistent with IBS (Rome III criteria) based on survey responses but had not received a diagnosis from a healthcare provider.
‡Individuals (57%, n=1094/1924) who had received a diagnosis from a healthcare provider; n values not provided for treatment percentages shown.
Source: Sayuk GS, et al. Am J Gastroenterol. 2017;112(6):892-899.
Pathophysiology of IBS
IBS is a heterogeneous condition, which most likely involves a complex change in the way the GI tract, GI microbiome, and immune and nervous systems interact.11,12 In addition to various other patient-specific factors as shown below, there is also a strong link between neuropsychiatric conditions (eg, depression, anxiety, migraine) and IBS that indicates the interaction between the GI tract and the nervous system may be altered.11,12
Various factors play a potential role in the pathophysiology of IBS11,12
Growing evidence supports the role of an altered GI microbiome in the pathophysiology of IBS. Specifically, several studies have indicated alterations in numbers or ratios of certain bacterial species in small intestine biopsies and fecal samples from patients with IBS compared with healthy individuals.13,14 These alterations, as well as metabolomic changes, contribute to the state of microbial imbalance known as GI dysbiosis.11
Gastrointestinal dysbiosis in IBS11
In those with GI dysbiosis, dietary factors or other insults may trigger increased intestinal permeability in the small intestine (eg, altered metabolomic profiles in patients with IBS-D vs healthy controls).12,13 Studies point to alleviation of IBS symptoms via modulation of the microbiota.11
Potential effects of increased intestinal permeability12
VIEW CONGRESS MATERIALS AND JOURNAL ARTICLES ON IBS-D.
VIEW CONGRESS MATERIALS AND JOURNAL ARTICLES ON IBS-C.
Overview
Chronic idiopathic constipation (CIC), or functional constipation, is classified as primary constipation, which refers to constipation occurring as a consequence of neuromuscular dysfunction of the colon or anorectal sensory-motor function.5 CIC is one of the most common primary constipation disorders.3,5
CIC comprises 3 subtypes—rectal evacuation disorders, slow-transit constipation, and normal-transit constipation, with normal-transit constipation being the most common.4,7 Symptoms include difficult, infrequent, or incomplete defecation occurring over a period of 6 months or longer and present during the previous 3 months.7 Abdominal pain and bloating may be present but are not predominant; therefore, patients with CIC do not meet the diagnostic criteria for irritable bowel syndrome with constipation (IBS-C).6 CIC and IBS-C are regarded by some to be constipation disorders along an abdominal pain continuum, rather than 2 distinct conditions.6,8
Medical Unmet Need in CIC
OTC, over the counter.
*The National GI Survey II was a cross-sectional, self-administered, online survey conducted May 3, 2020–June 24, 2020, that included 5334 US adults with CIC.
†OTC therapies included bisacodyl, docusate, fiber supplements, magnesium, polyethylene glycol 3350, and senna.
‡Prescription medications included lactulose, linaclotide, lubiprostone, plecanatide, prucalopride, and tegaserod.
§Satisfaction rated using a 5-point Likert scale.
Source: Liang J, et al. Am J Gastroenterol. 2023; Epub ahead of print.
Pathophysiology of CIC
The pathophysiology of the normal-transit subtype of CIC, or functional constipation, remains unclear and is likely multifactorial.4,7 Alterations in the gut microbiota may increase bile acid metabolism, promote methane production, and affect epithelial function, altering colonic motility and fluid secretion.7 Dietary and other lifestyle factors, as well as behavioral and psychological factors, may also be involved.6
Potential contributing factors in the pathophysiology of CIC7
VIEW CONGRESS MATERIALS AND JOURNAL ARTICLES ON CIC.
Irritable Bowel Syndrome (IBS)
Overview
Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction characterized by symptoms of recurrent abdominal pain and disordered defecation.9 The estimated prevalence of IBS in US adults is 4% to 5%, with rates higher among women.3,9 In the United States, new IBS cases are estimated to occur in 1% to 2% of the population annually.10
Diagnosis and common symptoms6,9
In patients with IBS, symptom onset must occur at least 6 months prior to diagnosis and be present during the past 3 months.
Abdominal pain is present at least once weekly (on average) in association with6:
- Change in stool frequency
- Change in stool form
- Relief or worsening of abdominal pain related to defecation
Bloating is a commonly reported symptom, but its presence is not necessary for diagnosis.6,9
Classification
Classification of IBS into subtypes, such as IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), is determined by the patients’ predominant bowel habit on days with abnormal bowel movements.6
Irritable bowel syndrome with diarrhea (IBS-D)
IBS-D is the most common IBS subtype.10 A positive diagnosis for IBS-D is recommended, with limited need for diagnostic testing in the absence of alarm features.6
Irritable bowel syndrome with constipation (IBS-C)
Patients with IBS-C primarily experience frequent constipation in addition to recurrent abdominal pain and bloating, which may require differential diagnosis to rule out other chronic constipation conditions.6
Additional subtypes include IBS with mixed bowel habits (IBS-M) and IBS unclassified (IBS-U).6 Patients with IBS-M report abnormal bowel habits that include both constipation and diarrhea. IBS-U includes patients who meet the diagnostic criteria for IBS but whose bowel habits cannot be categorized as one of the three other subtypes.6
Medical Unmet Need in IBS-D
*Individuals ≥18 years of age from a general US population who had experienced gastrointestinal symptoms who completed an online survey conducted September 1-15, 2014.
†Individuals who had symptoms consistent with IBS (Rome III criteria) based on survey responses but had not received a diagnosis from a healthcare provider.
‡Individuals (57%, n=1094/1924) who had received a diagnosis from a healthcare provider; n values not provided for treatment percentages shown.
Source: Sayuk GS, et al. Am J Gastroenterol. 2017;112(6):892-899.
Pathophysiology of IBS
IBS is a heterogeneous condition, which most likely involves a complex change in the way the GI tract, GI microbiome, and immune and nervous systems interact.11,12 In addition to various other patient-specific factors as shown below, there is also a strong link between neuropsychiatric conditions (eg, depression, anxiety, migraine) and IBS that indicates the interaction between the GI tract and the nervous system may be altered.11,12
Various factors play a potential role in the pathophysiology of IBS11,12
Growing evidence supports the role of an altered GI microbiome in the pathophysiology of IBS. Specifically, several studies have indicated alterations in numbers or ratios of certain bacterial species in small intestine biopsies and fecal samples from patients with IBS compared with healthy individuals.13,14 These alterations, as well as metabolomic changes, contribute to the state of microbial imbalance known as GI dysbiosis.11
Gastrointestinal dysbiosis in IBS11
In those with GI dysbiosis, dietary factors or other insults may trigger increased intestinal permeability in the small intestine (eg, altered metabolomic profiles in patients with IBS-D vs healthy controls).12,13 Studies point to alleviation of IBS symptoms via modulation of the microbiota.11
Potential effects of increased intestinal permeability12
VIEW CONGRESS MATERIALS AND JOURNAL ARTICLES ON IBS-D.
VIEW CONGRESS MATERIALS AND JOURNAL ARTICLES ON IBS-C.
Chronic Idiopathic Constipation (CIC)
Overview
Chronic idiopathic constipation (CIC), or functional constipation, is classified as primary constipation, which refers to constipation occurring as a consequence of neuromuscular dysfunction of the colon or anorectal sensory-motor function.5 CIC is one of the most common primary constipation disorders.3,5
CIC comprises 3 subtypes—rectal evacuation disorders, slow-transit constipation, and normal-transit constipation, with normal-transit constipation being the most common.4,7 Symptoms include difficult, infrequent, or incomplete defecation occurring over a period of 6 months or longer and present during the previous 3 months.7 Abdominal pain and bloating may be present but are not predominant; therefore, patients with CIC do not meet the diagnostic criteria for irritable bowel syndrome with constipation (IBS-C).6 CIC and IBS-C are regarded by some to be constipation disorders along an abdominal pain continuum, rather than 2 distinct conditions.6,8
Medical Unmet Need in CIC
OTC, over the counter.
*The National GI Survey II was a cross-sectional, self-administered, online survey conducted May 3, 2020–June 24, 2020, that included 5334 US adults with CIC.
†OTC therapies included bisacodyl, docusate, fiber supplements, magnesium, polyethylene glycol 3350, and senna.
‡Prescription medications included lactulose, linaclotide, lubiprostone, plecanatide, prucalopride, and tegaserod.
§Satisfaction rated using a 5-point Likert scale.
Source: Liang J, et al. Am J Gastroenterol. 2023; Epub ahead of print.
Pathophysiology of CIC
The pathophysiology of the normal-transit subtype of CIC, or functional constipation, remains unclear and is likely multifactorial.4,7 Alterations in the gut microbiota may increase bile acid metabolism, promote methane production, and affect epithelial function, altering colonic motility and fluid secretion.7 Dietary and other lifestyle factors, as well as behavioral and psychological factors, may also be involved.6
Potential contributing factors in the pathophysiology of CIC7
VIEW CONGRESS MATERIALS AND JOURNAL ARTICLES ON CIC.
Learn more about the signs, symptoms, and potential underlying mechanisms of overt HE, a complication of cirrhosis.
References
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Sayuk GS. Insights on disorders of gut-brain interaction. .
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Singh R, Zogg H, Ghoshal UC, Ro S. Current treatment options and therapeutic insights for gastrointestinal dysmotility and functional gastrointestinal disorders. .
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Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation global study. .
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Camilleri M, Ford AC, Mawe GM, et al. Chronic constipation. .
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Sharma A, Rao SSC, Kearns K, Orleck KD, Waldman SA. Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders. .
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Lacy BE, Mearin F, Chang L, et al. Bowel disorders. .
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Black CJ, Ford AC. Chronic idiopathic constipation in adults: epidemiology, pathophysiology, diagnosis and clinical management. .
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Bharucha AE, Sharma M. Painful and painless constipation: all roads lead to (a change in) Rome. .
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Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. .
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Palsson OS, Whitehead W, Törnblom H, Sperber AD, Simren M. Prevalence of Rome IV functional bowel disorders among adults in the United States, Canada, and the United Kingdom. .
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Ghaffari P, Shoaie S, Nielsen LK. Irritable bowel syndrome and microbiome; switching from conventional diagnosis and therapies to personalized interventions. J Transl Med. 2022;20(1):173.
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Holtmann GJ, Ford AC, Talley NJ. Pathophysiology of irritable bowel syndrome. .
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Tanaka Y, Yamashita R, Kawashima J, et al. Omics profiles of fecal and oral microbiota change in irritable bowel syndrome patients with diarrhea and symptom exacerbation. .
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Chung CS, Chang PF, Liao CH, et al. Differences of microbiota in small bowel and faeces between irritable bowel syndrome patients and healthy subjects. .
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