Irritable bowel syndrome is often described as a disorder of the gut-brain connection. A new genetic study suggests that picture may be too narrow.
The study, published in Gut, analyzed genetic and health data from nearly 2.8 million people across 22 biobanks and found that IBS risk may also overlap with pathways involved in lipid metabolism, triglyceride regulation and liver function. The findings do not mean IBS is caused by diet, that high triglycerides cause IBS symptoms or that lowering blood fats can treat the condition. Instead, they point to a possible biological pathway researchers may want to study more closely.
IBS affects more than 10% of the general population and can cause recurring abdominal pain, bloating, constipation and diarrhea. It’s considered a disorder of gut-brain interaction, meaning symptoms may be shaped by communication between the digestive system, nervous system and brain. Previous research has also linked IBS with anxiety, mood disorders and nerve signaling.
In this study, researchers conducted what they described as the most comprehensive genetic assessment of IBS to date. The international team compared people with and without IBS and identified 35 regions of the human genome associated with IBS risk.
Some of those genetic signals pointed to the brain and the enteric nervous system, the network of nerves that helps control the gut. But researchers also found overlap with cardiometabolic traits, including blood fats known as triglycerides.
“We have long known that IBS involves a complex dialogue between the gut and the brain, but these results show that the conversation includes the body's metabolic system too,” said Prof. Mauro D’Amato, professor of medical genetics at LUM University and Ikerbasque research professor at CIC bioGUNE. “The genetic link to triglyceride regulation and liver function gives us a completely new framework for understanding the condition.”
One signal of interest involved the GCKR gene, which helps regulate glucose and lipid metabolism in the liver. The variant highlighted in the study has already been linked to fat accumulation in the liver and increased triglyceride production. In this analysis, researchers identified it as a possible connection between liver metabolism and IBS risk.
That does not make IBS a liver disease or a blood-fat disorder. Genetic studies can help researchers spot biological patterns, but they do not automatically translate into treatment advice. For people living with IBS, the findings should not be read as a reason to start supplements, medications or restrictive eating plans aimed at triglycerides without medical guidance.
The study may be more useful as a step toward understanding why IBS can look so different from one person to another. Some people have symptoms tied to certain foods. Others experience flares linked to stress, hormones, infections or no obvious trigger at all. A more complete view of IBS biology could eventually help researchers identify subgroups of patients who may respond to different treatment strategies.
The researchers also explored whether existing drugs could affect gene-expression patterns associated with IBS risk. Some compounds identified in that analysis included cardiovascular and lipid-modifying drugs, raising the possibility that existing medications could someday be tested for specific IBS-related pathways.
“Our findings support a more integrated view of IBS that extends beyond the traditional gut-brain axis,” D’Amato said.
The research was supported by multiple public, nonprofit and research funding sources, including grants and programs connected to the National Institutes of Health, the National Heart, Lung, and Blood Institute, the All of Us Research Program, Wellcome, the Medical Research Council, the British Heart Foundation, the Research Council of Norway, the European Union’s Horizon 2020 program and the Million Veteran Program, among others.