Targeting gut–liver–kidney axis: microbiota-derived metabolites and therapeutic implications

TL;DR

This paper explores how gut microbiota metabolites affect liver and kidney health, and how targeting this gut-organ axis could lead to new therapies for metabolic and inflammatory diseases.

Contribution

The paper introduces a novel conceptual framework called the 'diet–microbiota–drug' triad for precision interventions targeting the gut-liver-kidney axis.

Findings

Microbial metabolites like SCFAs, BAs, TMAO, and tryptophan derivatives influence liver and kidney pathology through inter-organ signaling.

Therapeutic strategies such as FMT, dietary modulation, and pharmacological detoxification show promise in targeting the gut-liver-kidney axis.

Current challenges include interindividual variability and the need for multi-omics approaches to validate interventions.

Abstract

The gut–liver–kidney axis has emerged as a central regulatory network orchestrating metabolic, immune, and inflammatory homeostasis across organ systems. At its core lies the dynamic interplay between gut microbiota and host metabolism. Dysbiosis and impaired intestinal barrier integrity facilitate the systemic translocation of microbial metabolites—such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine-N-oxide (TMAO), and tryptophan derivatives—which profoundly influence hepatic lipid metabolism, renal immune responses, and overall metabolic balance. This review examines the molecular mechanisms through which gut-derived metabolites contribute to liver and kidney pathology, emphasizing inter-organ signaling and the pathological cascade of the “leaky gut–hepatic injury–renal dysfunction” loop. We critically evaluate emerging therapeutic strategies targeting this axis, including probiotic supplementation, fecal microbiota transplantation (FMT), dietary modulation (low-protein, high-fiber regimens), and pharmacological detoxification (e.g., AST‑120, molecular adsorbent recirculating systems [MARS]). Finally, we propose a conceptual “diet–microbiota–drug” triad to guide precision interventions, and discuss current challenges such as interindividual variability, the lack of standardized assessment tools, and the need for integrative multi‑omics and clinical validation. A deeper mechanistic understanding of gut–organ crosstalk may pave the way for innovative therapies to restore systemic metabolic homeostasis.

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