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Review
. 2023 Mar;72(3):590-599.
doi: 10.1136/gutjnl-2022-328515. Epub 2022 Oct 28.

Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

Michael Camilleri  1 , Guy Boeckxstaens  2
Affiliations
Review

Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

Michael Camilleri et al. Gut. 2023 Mar.

Abstract

Objective: To appraise the evidence that pathophysiological mechanisms and individualised treatment directed at those mechanisms provide an alternative approach to the treatment of patients with irritable bowel syndrome (IBS).

Design: A PubMED-based literature review of mechanisms and treatment of IBS was conducted independently by the two authors, and any differences of perspective or interpretation of the literature were resolved following discussion.

Results: The availability of several noninvasive clinical tests can appraise the mechanisms responsible for symptom generation in IBS, including rectal evacuation disorders, abnormal transit, visceral hypersensitivity or hypervigilance, bile acid diarrhoea, sugar intolerances, barrier dysfunction, the microbiome, immune activation and chemicals released by the latter mechanism. The basic molecular mechanisms contributing to these pathophysiologies are increasingly recognised, offering opportunities to intervene with medications directed specifically to food components, receptors and potentially the microbiome. Although the evidence supporting interventions for each mechanism is not at the same level of proof, the current state-of-the-art provides the opportunity to advance the practice from treatment based on symptoms to individualisation of treatment guided by pathophysiology and clinically identified biomarkers.

Conclusion: These advances augur well for the implementation of evidence-based individualised treatment for patients with IBS based on actionable biomarkers or psychological disturbances.

Keywords: irritable bowel syndrome.

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Conflict of interest statement

Competing interests: MC: consulting regarding irritable bowel syndrome for Ironwood; Protagonist Therapeutics; Zealand Biopharma; Aditum Bio; Invea Therapeutics and InveniAI.

Figures

Figure 1.
Figure 1.. Cellular mechanisms that are similarly or differentially expressed in colonic mucosa of patients with IBS-D compared with mucosa from patients with IBS-C. Mechanisms that appear in green boxes showed increased differential expression; those in orange boxes showed decreased expression; those in blue boxes showed similar expression in mucosa from IBS-D compared with mucosa from IBS-C.
Reproduced from reference , Am J Physiol Gastrointest Liver Physiol. 2022;323:G88-G101.
Figure 2.
Figure 2.. Clinical decision support tool developed by the AGA Guideline Committee for diarrhea or constipation in IBS.
Reproduced from references and . Note that tegaserod has since been withdrawn and is unavailable for prescription.
Figure 3.
Figure 3.. Therapeutic choices guided by pathophysiology and biomarkers
See this image and copyright information in PMC

References

    1. Camilleri M Peripheral mechanisms in irritable bowel syndrome. N Engl J Med 2012;367:1626–1635 - PubMed
    1. Nullens S, Nelsen T, Camilleri M, Burton D, Eckert D, Iturrino J, Vazquez-Roque M, Zinsmeister AR. Regional colon transit in patients with dyssynergic defecation or slow transit in patients with constipation. Gut 2012;61:1132–1139 - PMC - PubMed
    1. Wang XJ, Chedid V, Vijayvargiya P, Camilleri M. Clinical features and associations of descending perineum syndrome in 300 adults with constipation in gastroenterology referral practice. Dig Dis Sci 2020;65:3688–3695 - PMC - PubMed
    1. Chedid V, Vijayvargiya P, Halawi H, Park S-Y, Camilleri M. Audit of the diagnosis of rectal evacuation disorders in chronic constipation. Neurogastroenterol Motil 2019;31:e13510. - PMC - PubMed
    1. Nelson AD, Mouchli MA, Valentin N, Deyle D, Pichurin P, Acosta A, Camilleri M. Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic. Neurogastroenterol Motil 2015;27:1657–1666 - PubMed

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