Rhythmic Breathwork Recalibrates Stress-Induced Myeloid Immune Dysregulation: Integrated Multi-Omics Findings from a Mechanistic Randomized Controlled Trial

Abstract

Rhythmic breathwork rooted in yogic tradition has been associated with stress reduction, partly through modulation of autonomic balance via increased parasympathetic vagal activity. However, the integrated psycho-neuro-immune mechanisms through which these autonomic shifts translate into downstream immune and molecular changes remain incompletely characterized. We conducted a pilot randomized controlled trial of an 8-week Sudarshan Kriya Yoga (SKY) intervention in healthy adults (SKY n=30; control n=15; NCT05523414). Multi-modal outcomes including psychosocial assessments, heart rate variability (HRV), peripheral immune phenotyping, transcriptomics, and DNA methylation profiling were analyzed with baseline-adjusted models tailored to each modality. Session HRV increased progressively across the 75-minute SKY practice, indicating immediate vagal activation. Sleep HRV improvement, reduced general distress, and reduced anhedonic depression at week-8 were most evident among participants with elevated baseline inflammation, indicating response heterogeneity linked to inflammatory tone. SKY was associated with coordinated reductions in myeloid-associated inflammatory mediators, including M-CSF, MIP-1α, and TNF-α. Concurrently, monocytes exhibited significant preservation of CD163 receptor, consistent with a shift toward a regulatory myeloid phenotype and reduced emergency myelopoiesis rather than immune depletion. Multi-omics analyses revealed coordinated downregulation of NF-κB-dependent inflammatory signaling, upregulation of mitochondrial oxidative phosphorylation pathways, and suppression of glycolytic programs, a transcriptomic and epigenetic signature consistent with a parasympathetic-driven recalibration of inflammatory tone rather than non-specific immune suppression. These multi-modal findings support a psycho-neuro-immune model linking vagal activation to modulation of myeloid cell function and systemic inflammatory tone, with psychosocial effects most pronounced in individuals with elevated baseline inflammation.