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Investigating the Role of the Gut Phageome in Cardiovascular Disease

Liana Theodoridis 1 Buddhila Wickramasinghe 1, Tayla Gibson-Hughes 1 Vivian Tran 1, Grant R. Drummond 1, Maria Jelinic 1, Antony Vinh 1, Steve Petrovski 1

1 Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe

University, Bundoora, VIC 3086, Australia

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for an estimated 17.9 million deaths each year. Despite the multifaceted nature of CVD, hypertension is the predominant risk factor affecting 1 in 4 individuals worldwide. Recent studies show a significant link between gut microbiota, hypertension and CVD- associated conditions. Although the mechanisms driving these bacterial disruptions remains to be further explored, our studies suggest bacteriophages strongly influence these changes. Preliminary metagenomic analysis of angiotensin II-induced

hypertensive mice highlighted a decreased abundance of known probiotic Faecalibacterium prausnitzii and an increase of F. prausnitzii bacteriophages. Therefore, we hypothesise that alterations to the gut phageome contributes to the observed gut dysbiosis and pathogenesis of hypertension. This study aims to characterise the phageome in an alternative low renin, volume-dependent one kidney/deoxycorticosterone acetate/salt (1K/DOCA/salt) model of hypertension. Weekly blood pressure and faecal samples were obtained during the 21-day treatment period,

after which caecum samples were collected post-mortem. Bacteriophage DNA was subjected to metagenomic sequencing and subsequent taxonomic and abundance evaluation. Viral analysis highlighted an increase of Salmonella bacteriophages at the onset of disease, correlating with increased blood pressure and inflammation. Nontyphoidal Salmonella has been associated with cardiovascular infections, including endocarditis and pericarditis. Moreover, further investigation into the role of Salmonella

bacteriophages within these interactions is warranted. This research will unveil potential bacteriophage-based interventions that can re-establish a healthy microbiome and alleviate the current burden of hypertension-induced CVD.

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