Introducing ExHiBITT – Exploring Host microBIome inTeractions in Twins –, a colon multiomic cohort study

Abstract

Background: The colon is populated by approximately 1012 microorganisms, but the relationships between this microbiome and the host health status are still not completely understood. Here, our objective is to present the cohort characteristics of ExHiBITT – Exploring Host microBIome inTeractions in Twins – including i) biomedical phenotypes, ii) environmental factors and ii) colonoscopic findings. Methods: Participants from the TwinsUK cohort were recruited to study the interactions between the microbiome and host adaptive immunity. In total, 205 monozygotic twins were recruited from the wider TwinsUK cohort. They completed health questionnaires, and provided saliva, blood, colon biopsies from three different locations, caecal fluid, and two faecal samples. Results: A significant proportion of this apparently normal cohort had colonic polyps (28%), which are of interest as potential precursors of colorectal cancer, and, as expected, the number of polyps found was significantly correlated with BMI and age. Hitherto undiagnosed diverticulosis was also not infrequently found during colonoscopy (26%) and was associated with changes in Hybrid Th1-17 cells in the colon. Twin proband co-occurrence rate for diverticulosis (82%) was much higher than for polyps (42%). Familial factors affecting morphology or tolerance may contribute to the ease of endoscopy, as both the time to reach the caecum and pain perceived were highly concordant (proband concordance: 85% and 56%, respectively). Conclusions: We found the expected positive relationship between BMI and colonoscopic anomalies such as diverticular disease and polyps in the whole population, but within twin pairs this association was reversed. This suggests that familial factors confound these associations. Host and microbial next generation sequencing and metabolomics of the samples collected are planned in this cohort.