Abstract 003: Treatment With Ligilactobacillus Improves Gut Permeability And Hypertension In Spontaneously Hypertensive Rats

Abstract

Emerging evidence provide that a microbial imbalance (dysbiosis) is linked to several diseases including cardiovascular diseases. One of the features in hypertension is increased gut permeability. Supporting this, plasma endotoxin level is increased in hypertension and our previous study indicated that the plasma level of exotoxin from Streptococcus was increased in spontaneously hypertensive rats (SHR). Thus, we hypothesized that improvement of gut permeability in hypertension might be expected to prevent development of hypertension. In this study, we performed a 16S metagenome analysis using a synthetic long read sequencing approach by LoopSeq in feces from 10- to 15-week old SHR and Wistar-Kyoto rat (WKY). The analysis revealed that two difference species of anti-inflammatory microbiome were strongly decreased in SHR compared with WKY (n=4). We focus on the decreased Ligilactobacillus sp. (LAB) in SHR and oral administration of LAB to SHR for 2 weeks. SHR (10-15-week-old) exhibited increased gut permeability in proximal colon (P<0.05, n=4), which was improved by treatment with LAB for 2 weeks (P<0.05, n=4). The expression level of tight junction protein Claudin4 was decreased in SHR proximal colon (SHR vs WKY, 1.0±0.1 vs 1.7±0.2-fold increase to SHR, P<0.05, n=8), which was significantly increased by LAB treatment (SHR vs SHR+LAB, 1.0±0.1 vs 2.8±0.5-fold increase to SHR, P<0.05, n=10). Proximal colon in SHR increased the expression level of TNF-α mRNA (1.0±0.2 vs 0.2±0.1, P<0.05, n=8), which was reversed by LAB (1.0±0.2 vs 0.3±0.1, P<0.05, n=10). The level of mucin 2 was lower in SHR proximal colon (1.0±0.2 vs 4.3±0.8, P<0.05, n=8), which was not reversed by LAB (1.0±0.1 vs 0.8±0.3, n=10). We observed that high blood pressure in SHR was attenuated by treatment with LAB for 2 weeks (194.0±5.9 vs 149.7±4.8 mmHg, P<0.05, n=10). LAB also improved decrease in acetylcholine-induced relaxation in SHR mesenteric artery (P<0.05, n=5-8). We conclude that treatment of SHR with the decreased anti-inflammatory microbiota, LAB improves gut permeability in proximal colon possibly through inhibition of inflammation, resulting in lowering blood pressure. These results suggest that anti-inflammatory microbiome might be a new therapeutic target for hypertension.