Opportunistic detection of Fusobacterium nucleatum as a marker for the early gut microbial dysbiosis

Abstract Background Gastrointestinal microbiome has a great impact on human health and diseases. Fusobacterium nucleatum , an oral resident gram-negative microorganism, has been reported to differentially prevail in colorectal cancer (CRC). However, the effect of its enrichment was not clearly explored in terms of microbial homeostasis and stability at the early stage of disease development. Result Our analysis on longitudinal metagenomic data generated by the Integrative Human Microbiome Project (iHMP) showed that F. nucleatum significantly proliferated in IBD subjects with decrease in microbial diversity. Using non-parametric LDA effect size (LEfSe) algorithm, 12 IBD- and 14 non-IBD-specific marker species were identified. IBD-specific marker species were found more in the F. nucleatum -experienced subjects than in not-experienced ones. In addition, F. nucleatum experience severely abrogated intra-personal stability of microbiome in IBD patients and induced highly variable gut microenvironment. From the longitudinal comparison between prior and posterior distributions to F. nucleatum detection, 41 species could be regarded as indicative “classifiers” of dysbiotic state. Multiple logistic regression models were built to predict the probability experiencing F. nucleatum and showed that the high probability at the points following F. nucleatum observation was significantly associated with microbial dysbiosis. Finally, clustering all detected microbes based on the longitudinal distribution revealed that marker species for IBD and non-IBD conditions as well as pre-documented signature biomarkers of CRC were well distinguishable and could be utilized for explaining gut symbiosis and dysbiosis. Conclusion F. nucleatum opportunistically appeared under early gut dysbiosis, and a group of discriminative marker species associated with F. nucleatum , screened from the longitudinal analysis of microbial changes, was successfully applied to predict early microbiota alterations in both IBD and non-IBD conditions. Our prediction model and development of microbial biomarkers for estimating gut dysbiosis should provide a novel aspect of microbial homeostasis/dynamics and useful information on non-invasive biomarker screening.