Egg White Hydrolysate and Microbiome Synergy: A New Approach to Reducing Hypertension Progression

Hypertension is a risk factor for cardiovascular diseases, a leading cause of mortality worldwide. Hypertension pharmaceuticals address one of its mechanisms such as the renin-angiotensin system (RAS), vascular inflammation, and oxidative stress, overlooking the microbiome mechanism while presenting side effects. Natural alternatives such as egg white hydrolysate (EWH) have shown antihypertensive activity in vivo but have not targeted the microbiome mechanism to create a synergy to reduce hypertension progression. This study aimed to elucidate the microbiome's role through protein fermentation in reducing hypertension progression in synergy with the EWH anti-inflammatory and anti-hypertensive activity in vivo.

Spontaneously hypertensive rats (3-4 weeks old) were treated with egg white hydrolysate (SHR-EWH) for 12 weeks along with a control. Mean arterial pressure (MAP) was measured weekly by plethysmography. Feces were collected every 4 weeks along with blood, plasma, and tissue samples at the endpoint. RAS markers were analyzed by western blot and cytokines in plasma by a magnetic bead panel, and microbiome taxonomic analysis was performed through 16s rRNA gene sequencing. EWH showed anti-hypertensive activity by decreasing MAP after 12 weeks. MasR, responsible for vasodilation, was upregulated in the SHR-EWH aorta against the control. SHR-EWH had a higher abundance of Lachnospiraceae NK4A136 and Phascolarctobacterium genus. Both were identified as short-chain fatty acid producers, specifically propionate, previously shown as anti-inflammatory. Complementary in vitro gut microbiome fermentation showed an increased production with EWH digestion resistant fraction. The microbiome analysis indicates EWH synergistic anti-inflammatory bioactivity, potentially enabling a new dietary approach to reduce hypertension progression. The study supports a paradigm shift on microbiome protein fermentation as a novel alternative to reduce hypertension progression by acting synergistically with its anti-hypertensive, anti-inflammatory, and RAS-modulating bioactivities. Facilitating new applications in health and nutrition of dietary protein-derived alternatives.