Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease

To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease. [Display omitted] •The stability of the human microbiome varies among individuals and body sites•Highly individualized microbial genera are more stable over time•At each body site, coordinated microbial dynamics are observed in response to disease•Microbiome stability and skin microbial composition are altered with insulin resistance Zhou et al. explore the complex interactions between human microbiomes and their hosts across different body sites, revealing that microbiome stability and its impact on health are influenced by site-specific host factors. Their findings underscore the systemic nature of host-microbiome relationships, with significant implications for understanding metabolic diseases.