The gut microbiota instructs the hepatic endothelial cell transcriptome

Abstract

Summary The gut microbiota affects remote organ functions but its impact on organotypic endothelial cell (EC) transcriptomes remains unexplored. The liver endothelium encounters microbiota-derived signals and metabolites via the portal circulation. To pinpoint how gut commensals affect the hepatic sinusoidal endothelium, a magnetic cell sorting protocol, combined with fluorescence-activated cell sorting, was used to isolate hepatic sinusoidal ECs from germ-free (GF) and conventionally raised (CONV-R) mice for transcriptome analysis by RNA sequencing. This resulted in a comprehensive map of microbiota-regulated hepatic EC-specific transcriptome profiles. Gene Ontology analysis revealed that several functional processes in the hepatic endothelium were affected. The absence of microbiota influenced the expression of genes involved in cholesterol flux and angiogenesis. Specifically, genes functioning in hepatic endothelial sphingosine metabolism and the sphingosine-1-phosphate pathway showed drastically increased expression in the GF state. Our analyses reveal a prominent role for the microbiota in shaping the transcriptional landscape of the hepatic endothelium.

Editorial: Impact of the gut microbiota on cardiovascular medicine

“…A number of metaorganismal circuits have been reported to modulate different aspects of cardiovascular and cardiometabolic conditions, such as arterial hypertension and hypertensive end organ damage ( 3 , 4 ), lipid metabolism and atherosclerosis ( 5 , 6 ), glucose metabolism ( 7 ), platelet activation and thrombus formation ( 8 – 10 ), and ischemic heart disease ( 11 ). Remarkably, recent studies suggest that gut microbial composition also impacts on the efficacy of cardiovascular pharmacotherapy ( 12 , 13 ).…”

Role of Intestinal Microbes in Chronic Liver Diseases

“…Complementary multi-omics approaches could provide functional information along with gene sequencing data, and link microbial community signatures to molecular mechanisms of chronic liver diseases [ 126 , 128 , 129 ]. HTS could also be combined with other techniques, such as mass spectrometry [ 128 ], high-content imaging [ 130 ], cell sorting, and other molecular or non-molecular techniques [ 131 ]. It is possible to gain an in-depth understanding of the classification of microbiota, the relationship between changes in the abundance of different populations, and genetic variation.…”

The relationship between the number of stenotic coronary arteries and the gut microbiome in coronary heart disease patients

“…Sphingolipids are the basic components of cell membranes and organelles and include ceramide, sphingosine 1-phosphate (S1P), sphingosine, sphingomyelin, glycosphingolipids, and other molecules (Maceyka and Spiegel, 2014). Research showed that genes functioning in sphingosine metabolism and the S1P pathway showed drastically increased expression in the germ-free mice (Formes et al, 2021). Ceramide, the core product of sphingolipid metabolism, has long been considered a substance that causes atherosclerosis (Maceyka and Spiegel, 2014).…”