Abstract 62: Dietary Fibre Attenuates Hypertension By Reducing Macrophage Infiltration Via Gut Microbiota-Derived Metabolite-Sensing Receptors

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2021-09, Vol.78 (Suppl_1), p.A62-A62
• Main Authors: R Muralitharan, Rikeish, Dinakis, Evany, Xu, Chudan, Xie, Liang, Jama, Hamdi, Nakai, Michael E, Paterson, Madeleine, Salimova, Ekaterina, Bitto, Natalie, Kaparakis-Liaskos, Maria, Barlow, Chris, Creek, Darren, O'Donnell, Joanne, Mackay, Charles, Marques, Francine
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.78.suppl_1.62

High dietary fibre is fermented by the gut microbiota, resulting in the release of metabolites called short-chain fatty acids (SCFAs). Both fibre and SCFAs can reduce high blood pressure (BP) and its associated cardio-renal complications. However, the underlying mechanisms remain unclear. SCFAs can be detected by metabolite-sensing receptors GPR41 and GPR43, highly expressed by immune cells such as macrophages. We hypothesised that dietary fibre attenuates hypertension by modulating renal macrophage infiltration via metabolite-sensing receptors GPR41 and GPR43. To test this, we developed a novel GPR41/GPR43 double knockout (DKO) mice and characterised the cardiovascular and immune phenotype in both sham and angiotensin-II (Ang-II, 0.5mg/kg/day) treated DKO and wild-type (WT) mice (n=7-12 per group). WT Ang-II mice fed a high-fibre diet had significantly lower renal galectin-3 (p=0.0004), a macrophage marker, compared to WT Ang-II mice fed a low-fibre diet. Sham DKO mice on standard chow diet had no difference in BP or heart function but had higher kidney/tibia length index (p=0.049) and renal fibrosis levels compared to WT mice (p=0.004). Moreover, untreated DKO mice had higher numbers of renal macrophages compared to WT mice (p=0.002). Ang-II infusion of DKO mice resulted in higher BP (p