Depletion of core microbiome forms the shared background against diverging dysbiosis patterns in Crohn’s disease and intestinal tuberculosis: insights from an integrated multi-cohort analysis

Crohn’s disease (CD) and intestinal tuberculosis (ITB) are gastrointestinal (GI) inflammatory disorders with overlapping clinical presentations but diverging etiologies. The study aims to decipher CD and ITB-associated gut dysbiosis signatures and identify disease-associated co-occurring modules to evaluate whether this dysbiosis signature is a disease-specific trait or is a shared feature across diseases of diverging etiologies. Disease-associated gut microbial modules were identified using statistical machine learning and co-abundance network analysis in controls, CD and ITB patients recruited as part of this study. Module reproducibility was reinvestigated through meta-network analysis encompassing >5400 bacteriomes and ~900 mycobiomes. Subsequently, >1600 Indian gut microbiomes were analyzed to identify a central-core gut microbiome of 46 taxa, whose abundances aided in the formulation of an India-specific Core Gut Microbiome Score (CGMS) to measure the degree of core retention. Both diseases witness similar patterns of alterations in [alpha]-diversity, characterized by a significant reduction in gut bacterial (i.e., bacterial/archaeal) diversity and a concomitant increase in the fungal [alpha]-diversity. Specific bacterial taxa, along with the diverging mycobiome enabled distinction between the diseases. Co-abundance network analysis of these taxa, validated by integrated meta-network analysis, revealed a ‘disease-depleted’ module, consistent across multiple cohorts, with >75% of this module constituting the central-core Indian gut microbiome. CGMS robustly assessed the core-microbiome loss across different stages of gut inflammatory disorders, in Indian and international cohorts. While the disease-specific gain of detrimental bacteria forms an important component of gut dysbiosis, loss of the core microbiome is a shared phenomenon contributing to various GI disorders.