Eukaryotes and microbiota produce H₂S, using the same substrates and enzymes which constitute the reverse-trans-sulfuration and transsulfuration pathways. The homeostasis of gut microbiota impacts on the structural and functional integrity of gut epithelial barrier. Microbiota also serve as signalling sources to inform the host of the metabolism and functional changes. Microbiota dysbiosis negatively affect human health, contributing to diseases like obesity, diabetes, inflammatory bowel diseases, and asthma. Not by coincidence, these pathological conditions are also closely related to the abnormal metabolism and function of H₂S signalling.H₂S serves as a bacterial signal to the host and the host-produced H₂S impacts on the population and size of microbiota. These bi-directional interactions become especially important for the digestion and utilization of sulfur amino acid in diet. Dietary restriction of sulfur amino acid increases the endogenous production of H₂S by the host and consequently offers many health benefits. It, on the other hand, decreases the nutritional supply to the microbiota, which could be remedied by the co-application of prebiotics and probiotics. It is strategically sound to target the expression of H₂S-producing enzymes in different organs to slow aging processes in our body and promote better health.

  Objective  Cardiovascular diseases pose a major public health challenge in China, particularly in northern frigid regions where environmental stressors and limited access to healthcare access exacerbate disease risk. Both atrial fibrillation (AF) and hypertension are influenced by cold exposure. AF is a frequent cardiovascular complication of hypertension, yet their causal relationship remains incompletely defined. This study aimed to elucidate the mechanisms linking hypertension to AF in frigid regions, with an emphasis on identifying key genes driving disease progression.  Methods  We analyzed clinical data from 29,786 patients hospitalized at the First Affiliated Hospital of Harbin Medical University. Multivariate logistic regression was used to assess the association between hypertension and AF, and Mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) datasets. Whole-blood expression quantitative trait locus (eQTL) analysis and pathway enrichment were applied to identify hypertension-related genes. Single-cell RNA sequencing data from AF patients and hypertensive rat models were used to validate the role of TIE1. In addition, gut microbiota GWAS data were integrated to explore microbial influences on hypertension.  Results  Hypertension emerged as both an independent and causal risk factor for AF in frigid regions. Gene expression analyses identified TIE1 as a central mediator of hypertension-related effects, with elevated cardiomyocyte TIE1 expression associated with increased susceptibility to AF. In hypertensive rats, increased TIE1 expression correlated with higher AF incidence and enhanced inflammatory cytokine production, whereas cardiomyocyte-specific TIE1 knockdown reduced AF occurrence and attenuated atrial remodeling. Gut microbiota analysis further revealed that the abundance of Adlercreutzia was inversely correlated with TIE1 expression, suggesting a potential protective role mediated through microbial regulation of host gene expression.  Conclusion  These findings establish a causal link between hypertension and AF in cold northern regions and identify TIE1 as a pivotal mediator of this association. Targeting TIE1 may represent a therapeutic strategy for hypertension-associated AF. Moreover, the identification of Adlercreutzia as a modulator of TIE1 underscores the potential of the gut microbiota in preventing cardiovascular complications in frigid regions and opens promising avenues for future interventions.