Diurnal Timing Dependent Alterations in Gut Microbial Composition Are Synchronously Linked to Salt-Sensitive Hypertension and Renal Damage

Abstract

Alterations of diurnal rhythms of blood pressure (BP) and reshaping of gut microbiota are both independently associated with hypertension. However, the relationships between biorhythms of BP and gut microbial composition are unknown. We hypothesized that diurnal timing-associated alterations of microbial compositions are synchronous with diurnal rhythmicity, dip in BP, and renal function. To test this hypothesis, Dahl salt-sensitive (S) rats on low- and high-salt diets were examined for time of day effects on gut microbiota, BP, and indicators of renal damage. Major shifts in night and day patterns of specific groups of microbiota were observed between the dark (active) and light (rest) phases, which correlated with diurnal rhythmicity of BP. The diurnal abundance of Firmicutes, Bacteroidetes, and Actinobacteria were independently associated with BP. Discrete bacterial taxa were observed to correlate independently or interactively with one or more of the following 3 factors: (1) BP rhythm, (2) dietary salt, and (3) dip in BP. Phylogenetic Investigation of Communities revealed diurnal timing effects on microbial pathways, characterized by upregulated biosynthetic processes during the active phase of host, and upregulated degradation pathways of metabolites in the resting phase. Additional metagenomics functional pathways with rhythm variations were noted for aromatic amino acid metabolism and taurine metabolism. These diurnal timing dependent changes in microbiota, their functional pathways, and BP dip were associated with concerted effects of the levels of renal lipocalin 2 and kidney injury molecule-1 expression. These data provide evidence for a firm and concerted diurnal timing effects of BP, renal damage, and select microbial communities.

Targeting Gut Microbiota to Treat Hypertension: A Systematic Review

“…BP has a well-defined morning diurnal rhythm peak, dropping 10-20% at rest [11]. There is some evidence that gut microbiota shares synchronous time-of-day variation with BP that also correlates with the levels of circulating renal markers [11].…”

“…BP has a well-defined morning diurnal rhythm peak, dropping 10-20% at rest [11]. There is some evidence that gut microbiota shares synchronous time-of-day variation with BP that also correlates with the levels of circulating renal markers [11]. In rats, microbial pathways characterized with biosynthesis were upregulated at active phase of day (nighttime) while metabolite degradation pathways were upregulated at rest (daytime) [11].…”

“…There is some evidence that gut microbiota shares synchronous time-of-day variation with BP that also correlates with the levels of circulating renal markers [11]. In rats, microbial pathways characterized with biosynthesis were upregulated at active phase of day (nighttime) while metabolite degradation pathways were upregulated at rest (daytime) [11]. This finding may have an impact on clinical hypertension care also as reduced nocturnal systolic BP dipping has been associated with an increased risk of cardiovascular events and diurnal variation of BP may affect both medication timing and microbial-targeted strategies [11,46].…”

Human Stool Metabolome Differs upon 24 h Blood Pressure Levels and Blood Pressure Dipping Status: A Prospective Longitudinal Study

“…To the best of our knowledge, the BP dipping status has never been associated thus far with stool metabolome. One recent study performed on Dahl salt-sensitive rats has highlighted some correlations between fecal bacterial taxon (e.g., Sutterella) and the BP dipping of the animals [ 30 ]. Our group has recently reported on a cohort of 44 patients in which higher fecal SCFAs amounts were found in non-dippers compared with dippers [ 31 ].…”

Sexual dimorphism in the progression of type 2 diabetic kidney disease in T2DN rats

“…All tubes with samples were flash-frozen in liquid nitrogen and stored at -80°C until processing. Microbiome analysis was performed as previously described (8).…”