Immune-microbiome coordination defines interferon setpoints in healthy humans
Summary
Human immune systems are highly variable, with most variation attributable to non-genetic sources. The gut microbiome crucially shapes the immune system; however, its relationship with the baseline immune states of healthy humans remains incompletely understood. Therefore, we performed multi-omic profiling of 110 healthy participants through the ImmunoMicrobiome study. A factor-based integrative approach identified coordinated variation, revealing that the interferon response was amongst t
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# Immune-microbiome coordination defines interferon setpoints in healthy humans
*Published: 2026 May 14*
Human immune systems are highly variable, with most variation attributable to
non-genetic sources. The gut microbiome crucially shapes the immune system;
however, its relationship with the baseline immune states of healthy humans
remains incompletely understood. Therefore, we performed multi-omic profiling of
110 healthy participants through the ImmunoMicrobiome study. A factor-based
integrative approach identified coordinated variation, revealing that the
interferon response was amongst the most variable immune features in healthy
participants. Microbiome composition, pathways, and stool metabolites varied
concomitantly with interferon response pathways. Longitudinal data spanning more
than a year indicated the significant stability of these parameters within
individuals over time. Our study provides extensive data to examine the
relationship between the immune states and microbiomes of healthy individuals at
steady state, which paves the way for delineating inter-individual differences
relevant for disease susceptibility and responses to therapy.
DOI: 10.1016/j.cell.2026.02.003