Publications Using GEM Project Data
Novel Fecal Biomarkers that Precede Clinical Diagnosis of Ulcerative Colitis
In a collaboration between the Farncombe Institute, McMaster University and the GEM Project, researchers compared the fecal microbiota composition and activity levels of protein breakdown of samples from 48 subjects for remained healthy with 13 subjects who provided stool sample before and after developing Ulcerative Colitis . Pre-disease fecal samples exhibited increased elastase activity and protein breakdown that is seen in the fecal samples collected after they have developed UC. The researchers further studied the bacterial contribution and functional relevance of this discovered signature through the colonization of germ-free mice using the control, the pre- and post-disease fecal samples. Mice colonized with the pre- and post-disease samples showed higher activity of protein breakdown than those colonized with the control samples.
Galipeau HJ et al. “Novel fecal biomarkers that precede clinical diagnosis of ulcerative colitis”. Gastroenterology. 2020. Doi: 10.1053/j.gastro.2020.12.004
Increased Intestinal Permeability is Associated with Later Development of Crohn’s Disease
In this study, researchers examined if increased intestinal permeability, or leakiness of the gut, was associated with the future development of Crohn’s Disease (CD). They determined the leakiness by comparing the Lactulose Mannitol (LacMan) ratios of 1420 GEM subjects, with 50 of those who had gone on to develop CD. For more information on why scientists use the LacMan Ratio as a measure of intestinal permeability, please see below. Having an abnormally high LacMan ratio significantly increased the odds of developing CD. Ultimately finding that abnormal gut barrier function might serve as a biomarker for risk of CD onset.
Turpin, Williams et al. “Increased Intestinal Permeability Is Associated With Later Development Of Crohn’s Disease”. Gastroenterology, 2020. Elsevier BV, doi:10.1053/j.gastro.2020.08.005.
Analysis of Genetic Association of Intestinal Permeability in Healthy First-degree Relatives of Patients with Crohn’s Disease.
This study was looking to see if there are any genes that are linked to differences in intestinal permeability. The results suggest that specific genes have a limited impact on intestinal permeability.
Turpin, W et al. “Analysis of Genetic Association of Intestinal Permeability in Healthy First-degree Relatives of Patients With Crohn’s Disease.” Journal Of The Canadian Association Of Gastroenterology, vol 1, no. 2, 2018, pp. 59-60. Oxford University Press (OUP), doi:10.1093/jcag/gwy009.035.
FUT2 genotype and secretory status are not associated with fecal microbial composition and inferred function in healthy subjects.
FUT2 is a gene that is associated with a healthy intestinal function, and can regulate microbiota population. The gene is responsible for the formation of specific motifs present in the mucus that selectively allows the growth of certain microbes and limit foreign invaders to enter the body. This matters especially since individuals with CD are more likely not to have the correct version of the FUT2 gene and thus are not capable of producing protective motif of the mucus. In this study the GEM Project Scientists found that FUT2 is NOT associated with changes in diversity, composition, or function, of the bacteria of the gut microbiome. This suggests that FUT2 is contributing to the risk of CD independently of the gut microbiota.
Turpin, W et al. “FUT2 Genotype and Secretory Status Are Not Associated With Fecal Microbial Composition And Inferred Function In Healthy Subjects”. Gut Microbes, 2018, pp. 1-12. Informa UK Limited, doi:10.1080/19490976.2018.1445956.
Meta-analysis of Human Genome-Microbiome Association Studies: The MiBioGen Consortium Initiative.
The GEM Project contributed to the effort of identifying the influence of our genes on the composition of the microbiome. We participated in the MiBioGen Consortium Initiative comprised of 25 studies spread around the globe where similar types of samples were collected. A specific statistical tool was developed to better understand the relationship between genetics and the bacteria living in the intestines. With this collective effort, we hope to identify additional genetic signals that can explain the existing diversity of microbiota across different subject.
Wang, Jun et al. “Meta-Analysis Of Human Genome-Microbiome Association Studies: The Mibiogen Consortium Initiative”. Microbiome, vol 6, no. 1, 2018. Springer Science And Business Media LLC, doi:10.1186/s40168-018-0479-3.
Association of host genome with intestinal microbial composition in a large healthy cohort.
The intestinal bacteria (microbiota) are known to be influenced by the outside world, our environments, and our own bodies; the hosts. This study looks at the relationship between the intestinal microbiota (representing all bacteria living in our intestines), and the relationship these may have with our genes. Intestinal microbiota are known to be important in health and disease. Our study found that one third of the bacteria in the microbiota is heritable. This means that these heritable bacteria are more likely to be present in two individuals that are related. Our study found that 58 specific mutations in the subjects DNA were contributing to this heritability. Their influence was observed in 33 types of the intestinal bacteria. Four of these discoveries have been confirmed in another group of Subjects. This study was able to show that there are associations between specific genes and the bacteria lining the microbiome.
Turpin, W et al. “Association Of Host Genome With Intestinal Microbial Composition In A Large Healthy Cohort”. Nature Genetics, vol 48, no. 11, 2016, pp. 1413-1417. Springer Science And Business Media LLC, doi:10.1038/ng.3693.
Determinants of intestinal permeability in healthy first-degree relatives of individuals with Crohn’s disease.
In this study researchers were looking for genetic, environmental, and microbial factors that may be influence the intestinal permeability of our healthy subjects.
Why was intestinal permeability looked at? Intestinal permeability is a measure of “leakiness” of the gut. Increased intestinal permeability, or leakiness, may thus allow passage of gut contents (food, bacteria etc.) which can trigger an intestinal inflammatory response. Several studies have documented that changes in intestinal permeability can predict the course of IBD.
What is the LacMan Ratio? It is a tool used to assess intestinal permeability. To find this ratio, Subjects drink a solution that contains a large molecule (lactulose) that can only cross the gut barrier when it is damage. The solution also contains a small molecule (mannitol) that always crosses the barrier, independent of any damage to the gut barrier. So, by measuring the ratio of the two molecules (LacMan ratio), scientist can tells us how well the intestines are doing their job.
What did this study find? The LacMan ratio was found to not be heritable, meaning that genetics may only play a small role in healthy intestinal permeability. The ratio was also not affected by microbial composition. From this we can postulate that other factors such as the environment, would then likely have a greater impact on the deterioration of healthy intestinal permeability.
Kevans, D et al. “Determinants Of Intestinal Permeability In Healthy First-Degree Relatives Of Individuals With Crohnʼs Disease”. Inflammatory Bowel Diseases, vol 21, no. 4, 2015, pp. 879-887. Oxford University Press (OUP), doi:10.1097/mib.0000000000000323.
IBD Genetic Risk Profile in Healthy First-Degree Relatives of Crohn’s Disease Patients
This study compared the genetic composition of healthy individuals, those diagnosed with CD, and first-degree relatives of those with CD from the GEM Project. The results of this study show that first-degree relatives of those with CD have a greater genetic risk of CD in comparison to healthy individuals.
Kevans, D et al. “IBD Genetic Risk Profile In Healthy First-Degree Relatives Of Crohn’S Disease Patients”. Journal Of Crohn’s And Colitis, vol 10, no. 2, 2015, pp. 209-215. Oxford University Press (OUP), doi:10.1093/ecco-jcc/jjv197.