Multimodal analysis identifies microbiome changes linked to stem cell transplantation-associated diseases

Area of Science:

• Microbiology
• Immunology
• Computational Biology

Background:

• Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematological malignancies but is limited by complications like graft-versus-host disease (GVHD) and infections.
• Microbiome alterations are linked to allo-HSCT complications, yet previous studies using single techniques limit comprehensive understanding.

Purpose of the Study:

• To comprehensively define microbiome changes across multiple modalities (taxa, functions, metabolites) following allo-HSCT.
• To investigate the interactions within the microbiome (interactome) and their relationship with allo-HSCT complications.
• To identify microbial features that predict the development of GVHD and infections.

Main Methods:

• Integrated multi-omic approaches: 16S rRNA and shotgun sequencing, targeted and untargeted metabolomics.
• Machine learning and multivariate analyses to identify significant microbiome changes and interactions.
• Analysis of bacterial taxa, encoded functions, and metabolites in relation to allo-HSCT outcomes.

Main Results:

• Significant microbiome shifts observed in all modalities post-allo-HSCT, including depletion of beneficial Clostridiales and loss of key metabolic functions.
• Expansion of opportunistic pathogens like Staphylococcus species, potentially linked to reduced short-chain fatty acids (SCFAs).
• Specific microbial and metabolic alterations identified in patients who developed GVHD, such as depletion of anti-inflammatory commensals and immunoregulatory metabolites.

Conclusions:

• Identified specific microbiome changes and their interactions that precede allo-HSCT complications.
• These microbial features represent novel targets for developing microbiome-based strategies to prevent post-transplant diseases.
• The study highlights the importance of multi-omic and interactome analyses for understanding microbiome-driven complications.