The microbiome has emerged as a compelling therapeutic target with relevance across a wide range of local and systemic inflammatory diseases. Advances in microbial culturing, high-resolution metagenomics and experimental validation systems now enable mechanistic insight to directly inform the development of microbiome-based therapeutics. However, linking microbial community structure and function to host immune state and clinical outcomes remains a central challenge, particularly across distinct anatomical sites and developmental stages.
We have developed an integrated experimental framework that combines culture-based shotgun metagenomic sequencing with matched clinical and host profiling to investigate how microbial communities across multiple organs shape disease trajectories. Using a site-specific culturing strategy, we have established large, cohort‑resolved bacterial culture collections from infants, paediatric and adult patients, comprising more than 10,000 isolates. Leveraging these collections, we perform phylogeny‑aware, clade‑specific metagenomic analyses to identify functionally distinct microbial interactions specifically relevant to early-life development and inflammatory bowel disease. Resolving microbial variation reveals clade-specific microbe signatures associated with epithelial and inflammatory phenotypes. In vitro using patient specific isolates mirrors key clinical disease states and transcriptional profiles. Together, this integrated approach provides a scalable platform for connecting microbial ecology with host physiology and supports the rational design of targeted microbiome therapeutics.