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The gut microbiota has been implicated in the multifactorial pathophysiology of cardiometabolic diseases (CMD). Bacteriophage (phage) therapy offers precise modulation of the gut microbiota, targeting specific pathobionts while minimizing collateral damage to beneficial microbes. Studies highlight the therapeutic potential of phages in cardiometabolic diseases, including reductions in pathogenic bacteria and improvements in metabolic parameters. Challenges in developing phage therapy for CMD include identifying target bacteria, generating effective combinations of phages, product formulation, and strict production requirements. Temperate phages and phages with CRISPR-Cas machinery could alter (metabolic) the function of gut microbes to improve the CMD phenotype in the future. The worldwide prevalence of cardiometabolic diseases (CMD) is increasing, and emerging evidence implicates the gut microbiota in this multifactorial disease development. Bacteriophages (phages) are viruses that selectively target a bacterial host; thus, phage therapy offers a precise means of modulating the gut microbiota, limiting collateral damage on the ecosystem. Several studies demonstrate the potential of phages in human disease, including alcoholic and steatotic liver disease. In this opinion article we discuss the potential of phage therapy as a predefined medicinal product for CMD and discuss its current challenges, including the generation of effective phage combinations, product formulation, and strict manufacturing requirements. [ABSTRACT FROM AUTHOR]

• Using fecal microbiota transplantation, we observed that changes in the microbiome coincided with changes in fecal miRNA expression. • We identified 12 strong correlations between differentially abundant intestinal microbes and fecal miRNAs. • We did not observe a direct effect of specific miRNAs on their associated bacteria in an in vitro model. The intestinal gut microbiota is important for human metabolism and immunity and can be influenced by many host factors. A recently emerged host factor is secreted microRNA (miRNA). Previously, it has been shown that secreted miRNAs can influence the growth of certain bacteria and conversely, that shifts in the microbiota can alter the composition of secreted miRNAs. Here, we sought to further investigate the interaction between the gut microbiota and secreted miRNAs by the use of fecal microbiota transplantation (FMT). Subjects with the metabolic syndrome received either an autologous (n = 4) or allogenic (n = 14) FMT. Fecal samples were collected at baseline and 6 weeks after FMT, from which the microbiome and miRNA composition were determined via 16S rRNA sequencing and miRNA sequencing, respectively. We observed a significant correlation between the fecal miRNA expression and microbiota composition, both before and after FMT. Our results suggest that the FMT-induced shift in microbiota altered the fecal miRNA profile, indicated by correlations between differentially abundant microbes and miRNAs. This idea of a shift in miRNA composition driven by changes in the microbiota was further strengthened by the absence of a direct effect of specific miRNAs on the growth of specific bacterial strains. [ABSTRACT FROM AUTHOR]