Quantifying the impact of gut microbiota on inflammation and hypertensive organ damage

Abstract

Aims: Hypertension (HTN) can lead to heart and kidney damage. The gut microbiota has been linked to HTN, although it is difficult to estimate its significance due to the variety of other features known to influence HTN. Methods and Results: In the present study, we used germ-free (GF) and colonized (COL) littermate mice to quantify the impact of microbial colonization on organ damage in HTN. Four-week-old male GF C57BL/6J littermates were randomized to remain GF or receive microbial colonization. HTN was induced by subcutaneous infusion with angiotensin (Ang) II (1.44mg/kg/d) and 1% NaCl in the drinking water; sham-treated mice served as control. Renal damage was exacerbated in GF mice, whereas cardiac damage was more comparable between COL and GF, suggesting that the kidney is more sensitive to microbial influence. Multivariate analysis revealed a larger effect of HTN in GF mice. Serum metabolomics demonstrated that the colonization status influences circulating metabolites relevant to HTN. Importantly, GF mice were deficient in anti-inflammatory fecal short-chain fatty acids (SCFA). Flow cytometry showed that the microbiome has an impact on the induction of anti-hypertensive myeloid-derived suppressor cells and pro-inflammatory Th17 cells in HTN. In vitro inducibility of Th17 cells was significantly higher for cells isolated from GF than conventionally raised mice. Conclusion: Microbial colonization status of mice had potent effects on their phenotypic response to a hypertensive stimulus, and the kidney is a highly microbiota-susceptible target organ in HTN. The magnitude of the pathogenic response in GF mice underscores the role of the microbiome in mediating inflammation in HTN.

Antihypertensives and Antibiotics: Impact on Intestinal Dysfunction and Hypertension

“…45 Reintroduction of bacteria in germ-free mice was linked to increased anti-inflammatory SCFA production and attenuation of proinflammatory immune cell activation and organ injury, compared to germ-free mice, at baseline and following chronic Ang II infusion, this was more effective in the kidney than the heart. 46 Recently, it has been shown that SHR are immunoglobulin A deficient, which may contribute to the gut dysbiosis seen in this rat strain. 47,48 Together, this data shows dysbiosis may promote chronic inflammation and immune cell infiltration in tissues (heart, blood vessels, kidney, brain) to drive hypertension.…”