• Dr Joanne Delange

Genetic Study Highlights a Link Between Anxiety and Irritable Bowel Syndrome



Irritable Bowel Syndrome


Irritable bowel syndrome (IBS) is a common disorder that affects the digestive system. It affects around one in ten people and causes symptoms including abdominal pain, stomach cramps, bloating, constipation and diarrhoea. The cause of IBS is unknown and there is currently no cure, however it has been linked to food passing through your digestive system too quickly or too slowly, oversensitive nerves in your digestive system, stress and also a family history of IBS. IBS often runs in families and is also more common among people who are prone to anxiety.


The Gut-Brain Axis


The bi-directional cross-talk that occurs between the gut and the brain has been termed the gut-brain axis. The gut-brain axis links emotional and cognitive centres of the brain with peripheral intestinal functions. Research has described the importance of the gut microbiota in influencing gut-brain pathways. Furthermore, these pathways are bidirectional, which means that signalling occurs from the gut microbiota to the brain and also from the brain to the gut microbiota. This is evidenced in central nervous disorders such as autism and anxiety-depressive disorders, and also in gastrointestinal disorders such as IBS. In fact, IBS highlights the disruption in the complex relationship between the gut microbiota and the brain and furthering our understanding may provide novel therapeutic targets.


Shared Origins of IBS and Mental Health Disorders


An international team of researchers in the UK and Spain has now identified several genes that provide clues into the origins of IBS, showing that IBS and mood and anxiety disorders are genetically linked, with the gut-brain axis playing a key role. The team used a genome-wide association study to assess susceptibility to IBS. Using cases from the UK Biobank and the Bellygenes initiative, 53,400 participants with IBS were compared to 433,201 participants without IBS, all of European descent. The results were replicated in a 23andMe panel using 205,252 subjects with IBS and 1,384,055 subjects without IBS.


The study published in Nature Genetics found certain locations on six genes that are more common in people with IBS than controls. These genes are NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are known to be linked with mood and anxiety disorders. In addition, there were strong links between the risk of IBS and neuroticism, depression and insomnia. These genes are understood to be expressed in the brain tissue and the nerves that connect the brain to the gut, instead of the gut itself.


Previous attempts to understand the role of genes passed on from one family member to another play in a person's risk of developing IBS have been inconclusive. This study found that the impact of having the implicated gene variants on the risk of developing IBS was small, and that other factors including diet, stress, antibiotic use during childhood and learned behaviours all had a greater impact on risk. The authors also noted that these factors can be shared within families.


Professor Miles Parkes, the study co-senior investigator and consultant gastroenterologist from the University of Cambridge explains that this study shows that these conditions have shared genetic origins, with the affected genes possibly leading to physical changes in brain or nerve cells that in turn cause symptoms in the brain and symptoms in the gut. However, he was keen to point out that although IBS occurs more frequently in those who are prone to anxiety, they don't believe that one causes the other.


Genetic changes that have only subtle effects on IBS can provide clues about pathways to target therapeutically. Co-senior investigator Dr Luke Jostins from the University Oxford anticipates that future research will build on their discoveries, both by investigating the target genes identified and exploring the shared genetic risk across conditions to improve understanding of the disordered gut-brain interactions which characterise IBS'


Conclusions


This research highlights the close relationship between brain and gut health and paves the way for development of new treatments. Furthermore, this discovery might ultimately help with developing better tests and improve the diagnosis of IBS.


Nutritional Insight Archive


Nutritional Insight has previously investigated the links between the microbiota and the gut-lung axis, which you can read more about here.


References:


Eijsbouts C, et al (2021). Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nature Genetics volume 53, pages 1543–1552. Available at https://doi.org/10.1038/s41588-021-00950-8


Large-scale genetic study reveals new clues for the shared origins of irritable bowel syndrome and mental health disorders. University of Cambridge. Available at https://www.cam.ac.uk/research/news/large-scale-genetic-study-reveals-new-clues-for-the-shared-origins-of-irritable-bowel-syndrome-and

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