Spatial transcriptomics maps host-gut microbiome biogeography at high resolution

Area of Science:

• Microbiology
• Genomics
• Bioinformatics

Background:

• Interactions within the gut microbiome are crucial for its function.
• Existing tools for studying these interactions in situ lack resolution and sensitivity.
• Understanding host-microbial and intermicrobial dynamics is essential for gut health.

Purpose of the Study:

• To develop a high-resolution method for spatial sampling of gut microbiome-host interactions.
• To enhance the recovery and transcriptomic analysis of bacterial RNA, including low-abundance taxa.
• To investigate the spatial organization and interactions within the gut microbiome in a disease model.

Main Methods:

• Enzymatic in situ polyadenylation of bacterial and host RNA.
• Integration with spatial RNA sequencing for high-resolution transcriptomic analysis.
• Benchmarking against existing spatial transcriptomic workflows for sensitivity and resolution.

Main Results:

• The developed method achieves 1 µm resolution, significantly improving bacterial RNA recovery.
• Spatial transcriptomic analysis revealed the gut microbiome's biogeography based on intestinal location.
• Frequent, short-range intermicrobial interactions and tumor-associated alterations in the host-microbiome interface were observed.

Conclusions:

• This novel method provides unprecedented spatial insights into gut microbiome composition and function.
• It enables detailed study of host-microbe and intermicrobial interactions at the transcriptomic level.
• The technique is adaptable to commercial platforms, facilitating broader research into microbiome-related health and disease.