Hypertension drives microbial translocation and shifts in the fecal microbiome of non-human primates

Abstract

Accumulating evidence indicates a link between gut barrier dysfunction and hypertension. However, it is unclear whether hypertension dictates gut barrier dysfunction or vice versa and whether the gut microbiome plays a role. To better understand this relationship, first, we cross-sectionally examined hypertension and other cardio-metabolic risk factors and gut barrier function in a population of 150 nonhuman primates. Interestingly, the animals with hypertension showed evidence of gut barrier dysfunction (i.e., translocation of microbes through the gut wall), as indicated by higher plasma levels of lipopolysaccharide-binding protein (LBP)-1, compared to normotensive animals. Further, plasma LBP-1 levels were strongly correlated with diastolic blood pressure, independent of age and other health markers, suggesting specificity of the effect of hypertension on microbial translocation. In a subsequent longitudinal study (analysis at baseline, 12 and 27 months), hypertensive animals had higher plasma levels of LBP-1 at all the time points and greater bacterial gene expression in mesenteric lymph nodes compared to normotensive animals, confirming microbe translocation. Concomitantly, we identified distinct dysbiosis in the gut microbial signature of hypertensive versus normotensive animals at 12 and 27 months. These results suggest that hypertension drives microbial translocation in the gut and eventually unhealthy shifts in the gut microbiome, possibly contributing to poor health outcomes, providing further impetus for the management of hypertension. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/454379v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@2b2990org.highwire.dtl.DTLVardef@1b5e678org.highwire.dtl.DTLVardef@12de192org.highwire.dtl.DTLVardef@1344f6a_HPS_FORMAT_FIGEXP M_FIG C_FIG