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, 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 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. Using a microbial dysbiosis metric based on the German KINDRED cohort, we identified strong and generalizable gradients within and across different external IBD cohorts for validation. These community gradients correspond strongly with IBD pathologies, physiological manifestations of inflammation (e.g. Bristol stool score, ASCA IgA, ASCA IgG), and genetic risk for IBD. Anthropometric and medical factors influencing fecal 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 ectopically colonizing oral taxa (e.g. Veillonella sp. Cand. Saccharibacteria sp. Fusobacterium nucleatum) the distinct and chaotic IBD-specific communities. Weak community and physiological changes are further traceable in a small number of individuals, who developed IBD in the study's runtime. Our findings demonstrate broad-scale ecological patterns which indicate drastic state transitions of communities in IBD patients. These patterns appear to be universal across cohorts and influence physiological signs of inflammation, display increased resilience, but show only limited heritability/intrafamily transmission.
Keywords: 16S; Family Cohort; IBD; dysbiosis; inflammatory bowel disease; microbiota; oralization.