Gut microbiota dysbiosis and microbial metabolites impair renal function in sepsis-associated acute kidney injury

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Frontiers in Medicine Published June 6, 2026 Medically reviewed June 6, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note that gut microbiota dysbiosis and metabolites impair renal function in sepsis-associated acute kidney injury.

This narrative review explores the connection between gut microbiota dysbiosis and kidney injury in the context of sepsis. The scope includes human and animal studies regarding the impact of microbial changes on organ function. The authors synthesize findings on how loss of microbial diversity and expansion of pathobionts contribute to disease progression.

The review details compromised intestinal barrier integrity and impaired renal function as key outcomes. Specific microbial signatures include increased Clostridium asparagiforme and decreased Roseburia spp., alongside elevated uremic toxin-producing bacteria like Gordonibacter pamelaeae. These changes are linked to renal inflammation and fibrosis promoted by gut-derived metabolites including indoxyl sulfate, p-cresol sulfate, and trimethylamine N-oxide (TMAO).

The authors note that sepsis induces gut microbiota dysregulation which plays an important role in the development of sepsis-associated acute kidney injury. The practice relevance indicates that intestine-kidney crosstalk may provide a basis for the treatment of sepsis-induced organ injury and also provide new ideas for the treatment of sepsis-associated acute kidney injury. Limitations regarding specific study populations and adverse events were not reported in this source.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

BackgroundSepsis-associated acute kidney injury (SA-AKI) carries high morbidity and mortality, yet its pathogenesis remains incompletely understood. Emerging evidence underscores the gut-kidney axis as a critical pathway in SA-AKI development.ObjectiveThis review aims to synthesize current knowledge on how sepsis-driven gut dysbiosis compromises intestinal barrier integrity and contributes to SA-AKI, and to explore potential therapeutic strategies targeting the gut microbiota.MethodsA comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases for publications between 2005 and 2026. Studies focusing on gut-kidney crosstalk mechanisms in sepsis/AKI were included. Key findings from human and animal studies were summarized.ResultsSepsis induces marked gut dysbiosis characterized by loss of microbial diversity and expansion of pathobionts. This dysbiosis compromises intestinal barrier integrity, facilitating translocation of bacterial products such as lipopolysaccharide (LPS). Upon entering circulation, these mediators activate systemic inflammation and renal signaling cascades, including the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway, leading to tubular injury and impaired renal function. Recent human metagenomic studies have identified specific microbial signatures associated with AKI, such as increased Clostridium asparagiforme and decreased Roseburia spp., alongside elevated uremic toxin-producing bacteria like Gordonibacter pamelaeae. Additionally, gut-derived metabolites including indoxyl sulfate, p-cresol sulfate, and trimethylamine N-oxide (TMAO) have been implicated in promoting renal inflammation and fibrosis. Importantly, renal dysfunction further disrupts gut homeostasis, establishing a pathological gut–kidney feedback loop. Targeting the gut-kidney axis via fecal microbiota transplantation, probiotic supplementation, or short-chain fatty acid administration may offer novel therapeutic avenues.ConclusionsSepsis induces gut microbiota dysregulation play an important role in the development of SA-AKI. The intestine-kidney crosstalk may provide a basis for the treatment of sepsis-induced organ injury and also provide new ideas for the treatment of SA-AKI.