Elucidating a novel hypertension treatment approach through egg white hydrolysate and gut microbiome synergism in-vitro

Hypertension is a risk factor for cardiovascular diseases, a leading cause of mortality worldwide. Hypertension mechanisms include vascular inflammation, oxidative stress, and the gut microbiome. Current pharmacological interventions are associated with adverse events with few treatments, if any, reducing hypertension through the gut microbiome. Egg white hydrolysate after digestion has shown antihypertensive activity, with a fraction being unhydrolyzed. The effect of the digestion-resistant fraction in diverse gut microbiomes is not elucidated, with the potential to develop as a novel treatment. The purpose of this study was to evaluate EWH antioxidant, anti-inflammatory, and anti-hypertensive activity and its impact on diverse gut microbiomes using in-vitro cell culture and fermentation studies. Egg white hydrolysate (EWH) was prepared by sequential hydrolysis combining two different enzymes under alkaline and acidic conditions. EWH was further subjected to in vitro gastrointestinal digestion (EWH-GI). The <3000 Da fraction (EWH-GI-D) was evaluated for its bioactivity using endothelial cells along with in-vitro ACE inhibition. The >3000 Da fraction (EWH-GI-U) was subjected to in-vitro microbial fermentation using five microbiomes. Fermentation metabolites such as ammonia, short (SCFA), and branched-chain fatty acids (BCFA) were analyzed. EWH-GI-D showed anti-inflammatory activity by reducing the inflammation marker ICAM-1 in HUVEC cells at 100 µg/mL. No antioxidant activity was observed for any of the treatments. The ACE inhibition IC50 was significantly lower for EWH-GI-D at 1.6 mg/mL compared to EW-GI-D at 6 mg/mL. Gut microbiome detrimental metabolites such as ammonia and SCFA/BCFA were significantly lower in EWH-GI-U compared to peptone (control) except for propionate, which has shown anti-inflammatory activity through immune modulation. The results are promising as EWH could reduce hypertension progression by simultaneously modulating its mechanisms directly, and systematically via modulation of gut microbiome metabolites. The research expands egg white hydrolysate benefits while validating functional foods' gut microbiome modulation to delay hypertension progression.