Review Article
New insights into the pathogenesis and treatment of irritable bowel syndrome

https://doi.org/10.1016/j.advms.2016.11.001Get rights and content

Abstract

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGID), characterized by abdominal pain and a change in stool form that cannot be explained by structural abnormalities. Its prevalence ranges from 9 to 23% of the worldwide population. The pathophysiology of IBS is diverse and not well understood. Biopsychosocial concept assumes that the disease is a product of psychosocial factors and altered at multiple levels of gut physiology interactions. Some aetiological factors have been identified, yet. One of the most important is the disruption of brain-gut mutual communication that leads to visceral hypersensitivity. Also genetic and epigenetic factors are involved. Chronic stress may predispose to IBS as well as exacerbate its symptoms. Both quantitative and qualitative disorders of the gut microbiota are observed. There is also a relationship between the IBS symptoms and the intake of a specific type of food products. In the diarrhoea type of IBS the role of previous gastrointestinal infection is demonstrated. Recent studies have suggested that visceral hypersensitivity in patients with IBS may be secondary to the activation of the immune cells and low-grade inflammation. Clinical symptoms of IBS include abdominal pain and change in bowel habits as well as somatic and psychiatric comorbidities. IBS is diagnosed on the basis of Rome Diagnostic Criteria. Recently, their newest version (Rome IV) has been presented. The aim of this review is to summarize the past decade progress in IBS diagnosis, main pathophysiological aspects and therapeutic management strategy.

Introduction

Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders characterized by recurrent abdominal pain and change in bowel habits (constipation or/and diarrhoea). The symptoms occur at least 1 day per week in the last 3 months and should be associated with 2 or more of the following criteria: (1) related to defecation; (2) a change in the frequency of defecation; (3) a change of stool appearance [1].

The stool is assessed following the Bristol Stool Form Scale (BSFS), showing its 7 types: types 1 and 2 as constipation, 3 and 4 – normally formed stool of a healthy person, whereas types 5–7 correspond to diarrhoea [2].

According to the character of patient's stools assessed using BSFS, four types of IBS having comparable prevalence rates can be distinguished: IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant), IBS-M (mixed, i.e. alternating diarrhoea and constipation) and IBS-U (unsubtyped) [2], [3]. The IBS-C may be diagnosed if more than 25% of bowel movements is type 1 or 2 and less than 25% – type 6 or 7. IBS-D criteria require more than 25% of bowel movements type 6 or 7 and less than 25% – type 1 or 2. Patients with IBS-M should demonstrate mixed bowel habits with more than 25% of bowel movements type 1 or 2 and more than 25% – type 6 or 7. IBS-U is diagnosed when patient bowel habits cannot be categorized to any of 3 groups above [1]. It is, however, worthy of note that in approximately 75% of patients, the type of IBS may undergo some changes in a relatively short time [3].

IBS is widespread in developed countries, although its prevalence increases worldwide and it is estimated at 9–23% in the overall population [4]. The morbidity rate in the adult population is 200/100,000 people/year [5]. In European countries and in the USA, the prevalence rate of IBS is 7–30% of the population [6], with women being more frequently affected (2:1) [4], [7], [8]. Most patients at the time of diagnosis are under 50 [3]. The prevalence of IBS in a group of children aged 4–18 years is 8.8% [9]. Despite high prevalence of IBS, its aetiology and pathogenesis have not been fully explained, and the diagnostics may be difficult in some cases.

The disease was first described in 1849, but the first holistic concept of mind and body integration and its’ inseparability was proposed by Plato, Aristotle and Hippocrates. The first physician who suggested emotional changes could lead to medical disease development was Claudius Galen. In 20th century an experiment performed by Tom Almy indeed confirmed correlations between mood and gastric motility [4], [10].

For a long time IBS was classified as a psychiatric disorder due to a very high incidence of psychological distress or disturbances in these patients. In the 1980s the first diagnostic criteria of IBS were published by an group of experts working on functional gastrointestinal disorders (FGID) [10]. Currently, the disease is diagnosed according to IV Rome Criteria [1].

In this review we summarize the diagnosis, main pathophysiological aspects and therapeutic management strategy of IBS.

Section snippets

Clinical symptoms and criteria of IBS diagnosis

Diagnostic principles of gastrointestinal tract dysfunctions are defined in Rome IV Diagnostic Criteria published in 2016. According to them, IBS can be diagnosed when a patient complains of recurrent abdominal pain associated with 2 or more of the following criteria: (1) related to defecation; (2) associated with a change in the frequency of defecation; (3) associated with a change of stool appearance (Table 1). There are some differences in diagnostic criteria of IBS in adults, children and

Conclusion

IBS is a disease entity of complex aetiology and despite numerous studies, there is still a lot of questions and doubts both on its definition, pathophysiology, diagnostic criteria and management. From the pathological point of view, the exact mechanisms of visceral sensitivity in IBS has not been clarified, yet. It is not known which mediators and pathways underly sensitization of nociceptors and visceral sensitivity are involved in specific patients. Also the role of gut microbiota,

Conflict of interests

The authors declare no conflict of interests.

Financial disclosure

None declared.

References (152)

  • P. Holzer et al.

    Vagal afferent input from the acid-challenged rat stomach to the brainstem: enhancement by interleukin-1beta

    Neuroscience

    (2004)
  • M. Maes et al.

    Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut

    J Affect Disord

    (2012)
  • P. Holzer et al.

    Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis

    Neuropeptides

    (2012)
  • W.D. Heizer et al.

    The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review

    J Am Diet Assoc

    (2009)
  • S. Eswaran et al.

    Food: the forgotten factor in the irritable bowel syndrome

    Gastroenterol Clin North Am

    (2011)
  • A.M. Niec et al.

    Are adverse food reactions linked to irritable bowel syndrome?

    Am J Gastroenterol

    (1998)
  • D.A. Savaiano et al.

    Milk intolerance and microbe-containing dairy foods

    J Dairy Sci

    (1987)
  • S.W. Derbyshire

    A systematic review of neuroimaging data during visceral stimulation

    Am J Gastroenterol

    (2003)
  • F. Mearin et al.

    Bowel disorders

    Gastroenterology

    (2016)
  • M. El-Salhy

    Irritable bowel syndrome: diagnosis and pathogenesis

    World J Gastroenterol

    (2012)
  • L. Saha

    Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine

    World J Gastroenterol

    (2014)
  • M. El-Salhy et al.

    Endocrine cells in the ileum of patients with irritable bowel syndrome

    World J Gastroenterol

    (2014)
  • W. Marlicz et al.

    Zespół nadwrażliwego jelita - nadwrażliwe jelito czy nadwrażliwy umysł?

    Pol Merkur Lekarski

    (2012)
  • O. Grundmann et al.

    Irritable bowel syndrome: epidemiology, diagnosis and treatment: an update for health-care practitioners

    J Gastroenterol Hepatol

    (2010)
  • J.J. Korterink et al.

    Epidemiology of pediatric functional abdominal pain disorders: a meta-analysis

    PLoS One

    (2015)
  • D.A. Drossman

    Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV

    Gastroenterology

    (2016)
  • J.S. Hyams et al.

    Functional disorders: children and adolescents

    Gastroenterology

    (2016)
  • T.P. Black et al.

    “Red flag” evaluation yield in irritable bowel syndrome

    J Gastrointestin Liver Dis

    (2012)
  • F. Motamed et al.

    Red flags of organic recurrent abdominal pain in children: study on 100 subjects

    Iran J Pediatr

    (2012)
  • B.K. Sandhu et al.

    Irritable bowel syndrome in children: pathogenesis, diagnosis and evidence-based treatment

    World J Gastroenterol

    (2014)
  • M. Bellini et al.

    Irritable bowel syndrome: a disease still searching for pathogenesis, diagnosis and therapy

    World J Gastroenterol

    (2014)
  • P.C. Konturek et al.

    Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options

    J Physiol Pharmacol

    (2011)
  • S.J. Halpin et al.

    Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: systematic review and meta-analysis

    Am J Gastroenterol

    (2012)
  • M. El-Salhy et al.

    Is irritable bowel syndrome an organic disorder?

    World J Gastroenterol

    (2014)
  • P. Henderson et al.

    The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease

    Am J Gastroenterol

    (2012)
  • J. Kwiecien et al.

    Negative results of antiendomysial antibodies: long term follow up

    Arch Dis Child

    (2005)
  • E. Pyleris et al.

    The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome

    Dig Dis Sci

    (2012)
  • E.D. Shah et al.

    Abnormal breath testing in IBS: a meta-analysis

    Dig Dis Sci

    (2010)
  • P. Enck et al.

    Irritable bowel syndrome

    Nat Rev Dis Primers

    (2016)
  • R. Sood et al.

    Diagnosis of IBS: symptoms, symptom-based criteria, biomarkers or ‘psychomarkers’?

    Nat Rev Gastroenterol Hepatol

    (2014)
  • E.S. Kim et al.

    Colonoscopy as an adjunctive method for the diagnosis of irritable bowel syndrome: focus on pain perception

    J Gastroenterol Hepatol

    (2010)
  • C.Y. Francis et al.

    The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress

    Aliment Pharmacol Ther

    (1997)
  • G.L. Engel

    The need for a new medical model: a challenge for biomedicine

    Science

    (1977)
  • R.D. Moloney et al.

    Stress and the microbiota-gut-brain axis in visceral pain: relevance to irritable bowel syndrome

    CNS Neurosci Ther

    (2016)
  • G. Boeckxstaens et al.

    Fundamentals of neurogastroenterology: physiology/motility – sensation

    Gastroenterology

    (2016)
  • S.J. Brookes et al.

    Extrinsic primary afferent signalling in the gut

    Nat Rev Gastroenterol Hepatol

    (2013)
  • S.M. Collins

    Is the irritable gut an inflamed gut?

    Scand J Gastroenterol Suppl

    (1992)
  • G. Barbara et al.

    The intestinal microenvironment and functional gastrointestinal disorders

    Gastroenterology

    (2016)
  • R.L. Soares

    Irritable bowel syndrome: a clinical review

    World J Gastroenterol

    (2014)
  • N.P. Hyland et al.

    Microbiota-host interactions in irritable bowel syndrome: epithelial barrier, immune regulation and brain-gut interactions

    World J Gastroenterol

    (2014)
  • Cited by (69)

    • Functional food and nutraceuticals for the prevention of gastrointestinal disorders

      2023, Industrial Application of Functional Foods, Ingredients and Nutraceuticals: Extraction, Processing and Formulation of Bioactive Compounds
    • Vardenafil oral jellies as a potential approach for management of pediatric irritable bowel syndrome

      2021, Saudi Pharmaceutical Journal
      Citation Excerpt :

      This negatively affects their performance and quality of life and would consequently represent a burden on their normal daily activities (Rajindrajith et al. 2017). Unfortunately; researches in the field of pediatric neuro-gastroenterology couldn't yet reveal IBS pathophysiology, despite considering diet, genetics, and the disruption in mutual communication between brain and gut leading to visceral hypersensitivity, the most recognized risk factors (Black and Ford, 2020; Oświęcimska et al. 2017; Sinagra et al. 2016). To date, developing safe and effective treatments for IBS remains a challenge as no specific treatment is documented.

    • Increased serum BDNF and ProBDNF levels in children with irritable bowel syndrome

      2020, Journal of Psychosomatic Research
      Citation Excerpt :

      In the absence of detectable biomarkers, IBS has a purely symptom-based diagnosis. [3]. Furthermore, the diagnostic criteria for IBS have been revised over time [3,6]. The pathogenesis of IBS still remains unclear.

    View all citing articles on Scopus
    View full text