Hypertension promotes microbial translocation and dysbiotic shifts in the fecal microbiome of nonhuman primates

Abstract

Accumulating evidence indicates a link between gut barrier dysfunction and hypertension. However, it is unclear whether hypertension causes gut barrier dysfunction or vice versa, and whether the gut microbiome plays a role. To understand this relationship, first, we cross-sectionally examined 153 nonhuman primates(NHPs), mean age 16±0.4yr and 129(84.3%) were females for cardio-metabolic risk factors and gut barrier function. This analysis identified blood pressure and age as specific factors that independently associated with microbial translocation. We then longitudinally tracked male, age-matched spontaneously hypertensive NHPs to normotensives(n=16), mean age 5.8±0.5yr, to confirm hypertension-related gut barrier dysfunction and explore the role of microbiome by comparing groups at baseline, 12 and 27 months. Collectively, hypertensive animals in both studies showed evidence of gut barrier dysfunction(i.e.,microbial translocation), as indicated by higher plasma levels of lipopolysaccharide-binding protein (LBP)-1, when compared to normotensive animals. Further, plasma LBP-1 levels were correlated with diastolic blood pressure, independent of age and other health markers, suggesting specificity of the effect of hypertension on microbial translocation. In over 2 years of longitudinal assessment, hypertensive animals had escalating plasma levels of LBP-1 and greater bacterial gene expression in mesenteric lymph nodes compared to normotensive animals, confirming microbes translocated across the intestinal barrier. Concomitantly, we identified distinct shifts in the gut microbial signature of hypertensive versus normotensive animals at 12 and 27 months. These results suggest that hypertension contributes to microbial translocation in the gut and eventually unhealthy shifts in the gut microbiome, possibly contributing to poor health, providing impetus for the hypertension management.

Host‐Microbiota Communication in Spontaneously Hypertensive Rats Generates Unique IgA‐Coated Gut Microbes

“…Nonetheless, previous studies have demonstrated the important mutual interactions between gut microbiota and hypertension in the development of hypertension, and one could be an initiator that changes the other. 14 , 15 Our study identified 4 bacterial genera that could be important in driving the overactivation of the immune system in the SHR, which could be targeted for therapeutic purposes.…”

Visceral adipose microbial and inflammatory signatures in metabolically healthy and unhealthy nonhuman primates

“…Glycemic and lipid measures were performed as previously described [18]. Blood pressure was measured noninvasively [18], and circulating monocyte chemoattractant protein (MCP)‐1, C‐reactive protein (CRP, R&D Systems), microbial translocation (MT) biomarker lipopolysaccharide‐binding protein (LBP)‐1 (Hycult Biotech Inc.), fatty acid binding protein (FABP)‐1 (LSBio), and soluble monocyte differentiation antigen CD14 (R&D Systems) were measured in plasma according to the manufacturers' instructions in duplicate by enzyme‐linked immunosorbent assay (ELISA).…”

Regulatory effect of gut microbes on blood pressure

“…Increased F/B ratio is often used as an indicator of gut microbial dysbiosis 54 . An increased F/B ratio has been reported in hypertensive animal models such as SHRs, 8 Ang‐II‐induced rats, 8 PAH rats, 52 hypoxia‐induced pulmonary hypertensive mice, 55 Dahl salt‐sensitive hypertensive heart failure rats, 56 stroke‐prone spontaneously hypertensive rats, 20 high‐fat‐diet l ‐NAME‐induced rats, 57 hypertensive monkeys, 58 and patients with hypertension, 8 while a decrease of F/B ratio was observed in high‐fructose‐induced salt‐sensitive hypertensive rats 47 . The F/B ratio in these studies has been described in details in Table 3.…”