Genetics of Irritable Bowel Syndrome: Shifting Gear Via Biobank-scale Studies

Overview

Journal Nat Rev Gastroenterol Hepatol

Specialty Gastroenterology

Date 2022 Aug 10

PMID 35948782

Authors

Michael Camilleri

Alexandra Zhernakova

Isotta Bozzarelli

Mauro DAmato

Affiliations

Soon will be listed here.

Abstract

The pathophysiology of irritable bowel syndrome (IBS) is multifactorial and probably involves genetic predisposition and the effect of environmental factors. Unlike other gastrointestinal diseases with a heritable component, genetic research in IBS has been scarce and mostly characterized by small underpowered studies, leading to inconclusive results. The availability of genomic and health-related data from large international cohorts and population-based biobanks offers unprecedented opportunities for long-awaited, well-powered genetic studies in IBS. This Review focuses on the latest advances that provide compelling evidence for the importance of genes involved in the digestion of carbohydrates, ion channel function, neurotransmitters and their receptors, neuronal pathways and the control of gut motility. These discoveries have generated novel information that might be further refined for the identification of predisposed individuals and selection of management strategies for patients. This Review presents a conceptual framework, the advantages and potential limitations of modern genetic research in IBS, and a summary of available evidence.

Citing Articles

Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review.

Wang B, Cheng P, Jin B, Jiang Y, Wang Q, Xu H Int J Gen Med. 2024; 17:4141-4151.

PMID: 39308964 PMC: 11414632. DOI: 10.2147/IJGM.S474525.

Crisis in the gut: navigating gastrointestinal challenges in Gulf War Illness with bioengineering.

Collier C, Salikhova A, Sabir S, Foncerrada S, Raghavan S Mil Med Res. 2024; 11(1):45.

PMID: 38978144 PMC: 11229309. DOI: 10.1186/s40779-024-00547-2.

Human CAZyme genes polymorphism and risk of IBS: a population-based study.

Torices L, Zamfir-Taranu A, Esteban-Blanco C, Bozzarelli I, Bonfiglio F, DAmato M Gut. 2024; 74(2):329-331.

PMID: 38969488 PMC: 11874360. DOI: 10.1136/gutjnl-2024-333056.

The gut microbiome in disorders of gut-brain interaction.

Kraimi N, Ross T, Pujo J, Palma G Gut Microbes. 2024; 16(1):2360233.

PMID: 38949979 PMC: 11218806. DOI: 10.1080/19490976.2024.2360233.

Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism.

Camilleri M, Jencks K Expert Opin Drug Metab Toxicol. 2024; 20(5):319-332.

PMID: 38785066 PMC: 11139426. DOI: 10.1080/17425255.2024.2349716.

References

Drossman D, Tack J . Rome Foundation Clinical Diagnostic Criteria for Disorders of Gut-Brain Interaction. Gastroenterology. 2021; 162(3):675-679. DOI: 10.1053/j.gastro.2021.11.019. View

Ford A, Sperber A, Corsetti M, Camilleri M . Irritable bowel syndrome. Lancet. 2020; 396(10263):1675-1688. DOI: 10.1016/S0140-6736(20)31548-8. View

Drossman D, Hasler W . Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016; 150(6):1257-61. DOI: 10.1053/j.gastro.2016.03.035. View

Lewis S, Heaton K . Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997; 32(9):920-4. DOI: 10.3109/00365529709011203. View

Buono J, Carson R, Flores N . Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea. Health Qual Life Outcomes. 2017; 15(1):35. PMC: 5310011. DOI: 10.1186/s12955-017-0611-2. View

Frandemark A, Tornblom H, Jakobsson S, Simren M . Work Productivity and Activity Impairment in Irritable Bowel Syndrome (IBS): A Multifaceted Problem. Am J Gastroenterol. 2018; 113(10):1540-1549. DOI: 10.1038/s41395-018-0262-x. View

Camilleri M . Diagnosis and Treatment of Irritable Bowel Syndrome: A Review. JAMA. 2021; 325(9):865-877. DOI: 10.1001/jama.2020.22532. View

Palsson O, Drossman D . Psychiatric and psychological dysfunction in irritable bowel syndrome and the role of psychological treatments. Gastroenterol Clin North Am. 2005; 34(2):281-303. DOI: 10.1016/j.gtc.2005.02.004. View

Camilleri M . Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2012; 367(17):1626-35. DOI: 10.1056/NEJMra1207068. View

10.

Ohman L, Simren M . Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 2010; 7(3):163-73. DOI: 10.1038/nrgastro.2010.4. View

11.

Bennet S, Ohman L, Simren M . Gut microbiota as potential orchestrators of irritable bowel syndrome. Gut Liver. 2015; 9(3):318-31. PMC: 4413965. DOI: 10.5009/gnl14344. View

12.

Moayyedi P, Simren M, Bercik P . Evidence-based and mechanistic insights into exclusion diets for IBS. Nat Rev Gastroenterol Hepatol. 2020; 17(7):406-413. DOI: 10.1038/s41575-020-0270-3. View

13.

Lackner J, Ma C, Keefer L, Brenner D, Gudleski G, Satchidanand N . Type, rather than number, of mental and physical comorbidities increases the severity of symptoms in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2013; 11(9):1147-57. PMC: 3779619. DOI: 10.1016/j.cgh.2013.03.011. View

14.

DAmato M . Genes and functional GI disorders: from casual to causal relationship. Neurogastroenterol Motil. 2013; 25(8):638-49. DOI: 10.1111/nmo.12173. View

15.

Waehrens R, Ohlsson H, Sundquist J, Sundquist K, Zoller B . Risk of irritable bowel syndrome in first-degree, second-degree and third-degree relatives of affected individuals: a nationwide family study in Sweden. Gut. 2014; 64(2):215-21. DOI: 10.1136/gutjnl-2013-305705. View

16.

Camilleri M . Genetics and irritable bowel syndrome: from genomics to intermediate phenotype and pharmacogenetics. Dig Dis Sci. 2009; 54(11):2318-24. PMC: 2903621. DOI: 10.1007/s10620-009-0903-4. View

17.

Heitkemper M, Kohen R, Jun S, Jarrett M . Genetics and gastrointestinal symptoms. Annu Rev Nurs Res. 2012; 29:261-80. DOI: 10.1891/0739-6686.29.261. View

18.

Saito Y . The role of genetics in IBS. Gastroenterol Clin North Am. 2011; 40(1):45-67. PMC: 3056499. DOI: 10.1016/j.gtc.2010.12.011. View

19.

Mawe G, Hoffman J . Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013; 10(8):473-86. PMC: 4048923. DOI: 10.1038/nrgastro.2013.105. View

20.

Bellono N, Bayrer J, Leitch D, Castro J, Zhang C, ODonnell T . Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. Cell. 2017; 170(1):185-198.e16. PMC: 5839326. DOI: 10.1016/j.cell.2017.05.034. View