Gut Microbiota in the Hepato-Cardiorenal Axis: Microbial Metabolites, Inflammation, and Emerging Therapeutic Targets

To sustain systemic homeostasis, the gut microbiota manages immunological, metabolic, and inflammatory processes. Multiorgan diseases, especially those impacting the liver, kidney, and cardiovascular system through the hepato-cardiorenal axis, have been strongly associated with dysbiosis.

A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, Science Direct, and Google Scholar, with the focus on articles till 2025. Eligible sources included clinical trials, systematic reviews, and peer-reviewed academic publications that discussed metabolites, gut microbiota, and treatment approaches for diseases of the liver, kidney, and heart. A qualitative synthesis of the data indicated important mechanisms and potential treatments.

SCFAs have anti-inflammatory and intestinal barrier integrity-enhancing qualities, whereas uremic toxins and TMAO promote oxidative stress, fibrosis, and vascular dysfunction. Hepatic steatosis, insulin resistance, and systemic inflammation are all affected by the dysbiosis-induced bile acid imbalance. Microbiotatargeted therapies include fecal microbiota transplantation, fiber- or polyphenol-rich diets, probiotics, prebiotics, synbiotics, and pharmacological modification of bile acid or TMAO pathways, which have potential but need more comprehensive validation.

The findings show that, among other factors, gut metabolites-such as uremic toxins, bile acids, TMAO, and SCFAs - are key players in mediating inflammation and metabolic dysregulation across the hepato-cardiorenal axis. However, the lack of consistent treatment protocols and differences in microbiome composition limit the practical application of preclinical research that has clearly demonstrated the existence of mechanistic links. Future research should focus on long-term clinical outcomes, biomarker identification, and precise microbiome modifications to establish causation and improve therapy effectiveness.

The gut microbiota significantly influences the hepato-cardiorenal axis through metabolitemediated signalling. While therapeutic modulation shows promise, precision medicine approaches and highquality randomized trials are essential to tackle multi-organ metabolic and inflammatory diseases.