Alterations in Gut Archaea Composition and Their Bacterial Interactions Linked to Hypertension

Alterations in the gut microbiota have been linked to hypertension, with the role of archaea, despite being stable constituents, remaining largely unexplored. Shotgun metagenomic analyses of fecal samples were performed on 341 participants from 3 cohorts: discovery cohort (88 individuals), validation cohort 1 (175 individuals), and validation cohort 2 (78 individuals). Principal Coordinates Analysis (PCoA) based on Bray-Curtis distances revealed significant alterations in the composition of enteric archaea between control individuals and hypertensive patients (P < 0.05). Hypertensive groups showed reduced abundances of halophilic archaea (Halorhabdus, Halovivax, and Halorubrum_lipolyticum) and methanogenic archaea (Methanomassiliicoccus and Candidatus_Methanomassiliicoccus_intestinalis). Eleven archaea species, depleted in fecal samples from hypertensive patients, distinguished them from control individuals, with areas under the receiver operating characteristic curve of 0.85, 0.79, and 0.91 in the discovery, validation cohort 1, and validation cohort 2, respectively. Significant correlations were observed between these archaea and clinical data across cohorts. Additionally, a significant positive correlation in richness between gut bacteria and archaea suggests a close cross-kingdom synergy within the microbiome. This study highlights significant shifts in the archaeal populations of hypertensive patients, underscoring the potential of archaeal biomarkers in hypertension diagnosis and suggesting avenues for future therapeutic research.