Depletion of core microbiome forms the shared background against diverging dysbiosis patterns in CD and ITB - Insights from an integrated multi-cohort analysis
CD and ITB are GI inflammatory disorders with overlapping clinical presentations, but diverging etilogies. The study aims to decipher CD and ITB-associated gut dysbiosis signature and identify disease-associated co-occurring modules to evaluate whether this dysbiosis signature is a disease-specific trait or is it a shared feature across GI diseases of diverging etiologies.  Stool samples from controls, CD and ITB subjects were subjected to 16S(n=57) and ITS1(n=64) sequencing, to compare bacteriome/archaeome/mycobiome dysbiosis, between the two diseases. Co-abundance network analysis was performed on the differentially abundant taxa to identify disease-associated modules, which were re-investigated through meta-network analysis encompassing > 5,400 bacteriomes and ~900 mycobiome profiles. Following this, greater than 1,600 Indian gut microbiomes were analysed to identify an Indian gut microbiome core of 46 members, whose abundances aided in formulation of a Core Gut Microbiome Score (CGMS) to measure the degree of core retention.  With respect to controls, the extent of alterations in a and beta diversities of bacteriome/archaeome were similar in CD and ITB, however, the shifts in mycobiome diversity and profiles were more pronounced in ITB. Specific differential bacterial taxa, along with the diverging mycobiome enables distinction between two diseases. Co-abundance network analysis of these taxa, validated by an integrated meta-network analysis, revealed a 'disease-depleted' module, consistent across multiple cohorts. Greater than 75% of this module overlapped with the Indian gut microbiome core. CGMS robustly assessed the core microbiome loss across different stages of gut inflammatory disorders, in Indian as well as international cohorts. While diseases-specific gain of detrimental bacteria forms an important component of gut dysbiosis, the loss of the core microbiome is a shared phenomenon contributing to various GI disorders.