An international team coordinated by Mauro D'Amato, Ikerbasque research professor at CIC bioGUNE, has shown for the first time that the frequency of defecation is hereditary in humans, and that specific genetic profiles influence intestinal habits, as well as predisposition to irritable bowel syndrome. The discovery of genes that control bowel habits opens the door to new therapeutic targets for irritable bowel.
To carry out the research, 167,875 individuals from population cohorts in the United Kingdom (UK Biobank), the Netherlands (LifeLines-Deep), Belgium (Flemish Gut Flora Project), Sweden (PopCol) and the United States (Genes for Good), and their genetic makeup has been correlated with the questionnaire data, mainly in relation to a simple query about the number of times one opens the intestines every day (the "stool frequency", as they called it in the study).
Research staff have found that, among people with more or less frequent stools, specific DNA changes are more common than in the rest of the population. These changes, found in 14 regions of the human genome, involve several genes that have been studied in more detail: "We were surprised by the new findings, highlighting multiple molecules whose role in intestinal motility - the set of movements that make the journey of food through the gut - was already known from clinical studies, including communication between the brain and the gut" says Ferdinando Bonfiglio, first author of the study.
Some of the genes reported in the study produce neurotransmitters, hormones and other molecules that are especially active in the brain and nerve cells involved in the control of intestinal peristalsis - contractions and relaxations of the intestine - and even pharmaceutically directed to induce intestinal movements in studies previous. "These results are very exciting and warrant follow-up studies, as once stool frequency genes are unequivocally identified, we may have a battery of new drug targets that can be exploited for the treatment of constipation, diarrhea and common dysmotility syndromes, such as irritable bowel syndrome" explains Mauro D'Amato.
High prevalence of irritable bowel syndrome
The frequency with which people move their intestines is important for well-being and reflects the proper functioning of the gastrointestinal tract in digesting and absorbing nutrients, while excreting waste products of digestion and toxic substances. Irregular bowel habits and impaired bowel motility, including constipation and diarrhea, often occur in common gastrointestinal conditions such as irritable bowel syndrome, a disorder that affects 10% of the population worldwide.
The precise mechanisms that regulate peristalsis (the action of the intestinal muscles that push food and feces along the gastrointestinal tract), as well as the reasons why they are disturbed in irritable bowel syndrome, are unknown. Research shows that the solution may be hidden in our genome.
The research team has also revealed evidence of a common genetic background for stool frequency and irritable bowel syndrome, and that this information can be used to identify people at increased risk of disease. The revelation was most evident in the case of irritable bowel syndrome characterized predominantly by diarrhea.
The researchers translated the genetic findings of their study into simple numerical values (called "polygenic scores"), to estimate the probability of having an altered stool frequency in each individual. Using data from the UK Biobank, they showed that people with higher polygenic scores were up to 5 times more likely to suffer from irritable bowel syndrome characterized predominantly by diarrhea than the rest of the population. "The genetic information and polygenic scores obtained in this study can be refined and eventually contribute to the classification of patients in different treatment groups, in the hope that it will lead to better therapeutic precision that achieves intestinal dysmotility and altered bowel habits return to normal. This would be a great step forward in combating irritable bowel syndrome, a common condition for which there is currently no effective treatment that works for all cases", concludes researcher Mauro D'Amato.
International research
A large number of institutions have participated in the research, such as CIC bioGUNE, Karolinska Institutet, Monash University, Mayo Clinic, Broad Institute, University of Michigan, University of Groningen, University of Oxford, University of Cambridge, University of Gothenburg, VIB Leuven, Christian Albrechts University of Kiel and others. The research has also received funding and support from the Department of Health of the Basque Government, the Ministry of Economy and Competitiveness of Spain, the Swedish Research Council, BBMRI-LPC, the Dutch government and the Dutch Organization for Scientific Research, the government Flemish, the Flanders Odysseus research fund-program, King Baudouin Foundation, FP7 METACARDIS, VIB, Rega Institute for Medical Research, and KU Leuven.
Publication
Bonfiglio et al. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome. Cell Genomics December 8th.
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