Nat Rev Gastroenterol Hepatol. 2022 Aug 10. doi: 10.1038/s41575-022-00662-2.Online ahead of print.

Michael Camilleri ¹, Alexandra Zhernakova ², Isotta Bozzarelli ³, Mauro D'Amato ^4 5 6

Author information

¹Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

²Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.

³Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain.

⁴Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain. damato@lum.it.

⁵Ikerbasque, Basque Foundation for Science, Bilbao, Spain. damato@lum.it.

⁶Department of Medicine and Surgery, LUM University, Casamassima, Italy. damato@lum.it.

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, neurotraansmitters 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.