Strain-level analysis of microbial community and detection of mutually exclusive relationships uncover complexity of inflammatory bowel disease

Abstract Background Despite intraspecies variation in ecological interaction and cellular function, most analytical methods for microbial communities that use the 16S rRNA gene are employed at the taxonomic level. Further, methods that detect positive or negative relationships between microbes such as Pearson correlation coefficient are generally applicable for linear correlations. Results We present METATEA for the analysis of community members with identical 16S rDNA sequences to define intraspecies groups, and for the calculation of exclusive correlation coefficient (ECC) to detect mutually exclusive relationships. Proportional variation of identical sequence groups in each disease subtype was revealed using a 16S rDNA data set of inflammatory bowel disease (IBD) samples. Conclusions Results at the identical sequence level complied with and outperformed those at the species or genus levels. Intraspecies variation was prevalent within Faecalibacterium prausnitzii , suggesting that some strains might be associated with diseases although it is known to be abundant in the human gut microbiota of healthy adults. IBD samples were categorized into two groups based on the ratios of certain Bacteroides vulgatus -like sequences. ECC identified strains antagonistic to disease-associated bacteria, thus proving their potential as probiotics in precision medicine. Klebsiella pneumoniae showed exclusive relationships with various bacteria, and its proportion was associated with bacterial diversity and Crohn’s disease. We expect METATEA to allow high resolution analysis of microbial communities and easy identification of pathogen-antagonistic probiotic microbes.