Presentation Information

[P02-915]TACM-seq Reveals Functional Host-Microbiome Interactions Through Integrated Epigenomic-Microbial Profiling

○Qing Ma1 (1. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (China))
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Keywords:

Host-microbiome interactions

Host-microbiome interactions are critical in immunity, infection, and cancer. However, their functional impact on host cells remains poorly understood due to the lack of methods that can simultaneously enable sensitive microbial detection and host regulatory profiling. To address this, we developed Transposase-Accessible Chromatin and Microbiome sequencing (TACM-seq), a chromatin-targeted approach that simultaneously profiles host epigenomes and tissue-resident microbiota. TACM-seq achieves exceptional microbial detection sensitivity and broad taxonomic coverage , enabling robust microbial profiling from diverse host-dominated samples across mammalian, plant, and insect systems. By concurrently mapping host chromatin accessibility, TACM-seq provides a direct functional readout of host responses to microbial presence. Applying TACM-seq to 23 cancer types from human pan-cancer cohorts, we uncover a key principle: microbial abundance alone is a poor predictor of host impact. Instead, TACM-seq identifies functionally relevant microbes directly linked to host response and chromatin remodeling. In colorectal cancer, elevated Fusobacterium nucleatum correlates with widespread chromatin remodeling, particularly at genes regulating Wnt signaling, extracellular matrix remodeling, and immune activation. At single-cell resolution, TACM-seq reveals Mycoplasma pulmonis enrichment within neutrophils and macrophages in the mouse olfactory epithelium, defining distinct host epigenetic states that track with intracellular microbial load. Together, TACM-seq establishes a unified, high-resolution framework for decoding host-microbe interactions, revealing microbial drivers of disease and their epigenetic mechanisms across cancer, infection, and homeostasis.

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