Endometriosis and gut disorders have a genetic link

Scientists have identified a genetic link between endometriosis and several digestive disorders, including irritable bowel syndrome (IBS).  

Endometriosis, which affects roughly 1 in 10 reproductive-age women, is caused by the growth of tissue that resembles the lining of the uterus in other parts of the body, such as the fallopian tubes, ovaries, bladder or bowel. The disease can cause cysts, severe cramping, heavy periods and infertility. It is also commonly associated with gastrointestinal (GI) issues, although the relationship between endometriosis and common GI disorders is not well understood. 

In a new study, published Thursday (Oct. 26) in the journal Cell Reports Medicine, scientists found observational evidence from a dataset of almost 190,000 women that suggests those with endometriosis are at a higher risk of having certain GI conditions, including diseases of the gut. 

They also identified specific regions of the genome that contain key gene variants linked to both endometriosis and each of these GI conditions. In the future, the genetic data could be used to help make new drugs or repurpose existing ones to treat GI problems and endometriosis simultaneously, the researchers wrote in their report. 

Related: Endometriosis may be caused by common gut bacteria, small study suggests

"I was excited to read this study as it was the first one to provide some really definitive evidence that there were genetic associations between endometriosis and some gastrointestinal disorders — notably IBS," Philippa Saunders, a professor in the Centre for Inflammation Research at the University of Edinburgh, told Live Science in an email. Saunders was not involved in the research, but she reviewed the paper. 

"This study provides a genetic link for the risk of developing these conditions that frequently occur together," Dr. Linda Guidice, a professor of reproductive sciences at the University of California, San Francisco who wasn't involved in the research, told Live Science in an email. 

"Moreover, the data provide insights into shared biological pathways that could serve for novel drug discovery to treat these disorders," she said. 

To uncover the links between endometriosis and gut diseases, the study authors first looked at data from 188,461 women in the U.K. Biobank, a large repository of health and genetic data from U.K. adults. The authors found that, compared with women without endometriosis, women with the disease were twice as likely to also have a diagnosis of IBS, a cluster of symptoms that affect the digestive system, as well as 1.4 times as likely to have a diagnosis of gastroesophageal reflux disease (GERD), a serious, chronic form of acid reflux. 

The authors then analyzed data from published genome-wide association studies (GWAS), which look for links between specific versions of genes and a given trait. This analysis revealed genetic correlations between endometriosis and IBS and GERD, as well as peptic-ulcer disease (PUD), in which the lining of the GI tract is eroded by stomach acid or digestive enzymes. They also uncovered specific correlations when they lumped GERD and PUD together in a group they called "GPM," since both conditions are acid-related and share medications. 

The genes associated with a higher risk of developing both IBS and endometriosis were found in three regions within the genome, and included, for example, the MYSM1 gene that plays a role in immune function. Genes linked to GPM and endometriosis were spread across six regions and included the RERG gene, which is regulated by the hormone estrogen. Another four genome regions were potentially associated with endometriosis, IBS and GPM. 

Interestingly, the study provided genetic support for the idea that certain drugs that are either already being used to treat GI conditions or being tested in clinical trials could also be helpful for endometriosis, or vice versa. For instance, the drug Proglumide targets a protein produced by the CCKBR gene and is already used to treat GERD and PUD, but the genetic data hint that it could be repurposed to treat endometriosis, the authors argue. Likewise, Pentoxifylline targets products of the PDE4B gene and has been tested for IBS and endometriosis, although it's unclear whether it's effective for the latter. 

The study had several limitations, however. 

For example, it considered endometriosis to be one disease, but there are different subtypes of the condition that could predispose people to different gastrointestinal disorders, Sally Mortlock, senior author of the study and a research fellow at the University of Queensland in Australia, told Live Science. In addition, the study investigated these conditions only at the molecular level, meaning "a lot more work" is needed to determine how these genes contribute to the development of these diseases in the body, Mortlock said. 

Nevertheless, she hopes the study will raise awareness of the overlap between endometriosis and GI diseases.

"If women present to their GP [general practitioner] with these gastrointestinal symptoms, they should be investigated not only for any gastrointestinal diseases, but also for endometriosis," Mortlock said.