Hypertension status associated with reduced gut archaeal richness and distinct community structure in a cohort of 246 samples.

Background: Hypertension is a major global health challenge and a leading contributor to cardiovascular morbidity and mortality. Increasing evidence indicates that the gut microbiota contributes to the development and progression of hypertension. However, the role of gut archaea, an understudied component of the microbiome, remains poorly defined. Methods: A total of 246 fecal metagenomic samples from two independent cohorts were analyzed, including 83 healthy controls and 163 individuals with hypertension. Gut archaeal composition, diversity, and interaction networks were assessed, and a diagnostic model was constructed using random forest. Results: Compared with healthy controls, individuals with hypertension exhibited significantly reduced archaeal richness (Chao1 index, P = 0.0024) and distinct community structure (Adonis, P = 0.011). Hypertension status was a major host factor associated with variation in archaeal community composition. Methanobacteriota was the dominant archaeal phylum in both groups. However, key methanogenic archaea, including Methanobrevibacter_A_smithii, Methanosphaera_sp900322125, and Methanomassiliicoccus_A_sp905203995, were significantly depleted in HTN. Hypertension also altered the correlations between gut archaea and clinical indicators, including blood pressure and lipid parameters, and markedly reshaped archaeal-archaeal and archaeal-bacterial interaction networks. A diagnostic model based on three core methanogenic archaeal taxa achieved an AUC of 0.945 in the combined cohort and demonstrated strong performance in the two independent cohorts (AUC = 0.858 and 0.999). Conclusions: This study provides the first comprehensive characterization of gut archaeal dysbiosis in hypertension. Reduced methanogenic archaea and remodeled cross-domain networks are hallmarks of hypertension. Gut archaeal signatures serve as promising noninvasive biomarkers.