First Insights into microbial changes within an Inflammatory Bowel Disease Family Cohort study

Background: The prospective Kiel Inflammatory Bowel Disease (IBD) Family Cohort Study (KINDRED cohort) was initiated in 2013 to systematically and extensively collect data and biosamples from index IBD patients and their relatives (e.g., blood, stool), a population at high risk for IBD development. Regular follow-ups were conducted to collect updated health and lifestyle information, to obtain new biosamples, and to capture the incidence of IBD during development. By combining taxonomic and imputed functional microbial data collected at successive time points with extensive anthropometric, medical, nutritional, and social information, this study aimed to characterize the factors influencing the microbiota in health and disease via detailed ecological analyses. Results: Using two dysbiosis metrics (MD-index, GMHI) trained on the German KINDRED cohort, we identified strong and generalizable gradients within and across different IBD cohorts, which correspond strongly with IBD pathologies, physiological manifestations of inflammation (e.g., Bristol stool score, ASCA IgA/IgG), genetic risk for IBD, and general risk of disease onset. Anthropometric and medical factors influencing transit time strongly modify bacterial communities. Various Enterobacteriaceae (e.g., Klebsiella sp.) and opportunistic Clostridia pathogens (e.g., C. XIVa clostridioforme), characterize in combination with ectopic oral taxa (e.g. Veillonella sp., Cand. Saccharibacteria sp., Fusobacterium nucleatum) the distinct and chaotic IBD-specific communities. Functionally, amino acid metabolism and flagellar assembly are beneficial, while mucolytic functions are associated with IBD. Conclusions: Our findings demonstrate broad-scale ecological patterns which indicate drastic state transitions of communities into characteristically chaotic communities in IBD patients. These patterns appear to be universal across cohorts and influence physiological signs of inflammation, display high resilience, but show only little heritability/intrafamily transmission.