Is there a correlation between TMAO plasma levels and archaea in the gut of patients undergoing hemodialysis?

Abstract

Purpose: Patients with chronic kidney disease (CKD) present high plasma levels of trimethylamine N-oxide (TMAO), a uremic toxin produced by gut microbiota associated with atherogenesis. Experimental studies have shown that certain methanogenic archaea members use trimethylamine (TMA), the TMAO precursor in the human gut, to produce methane, suggesting a potential strategy to reduce TMAO levels in patients with CKD. Hence, this study aimed to evaluate the association of Archaea in the gut microbiota and TMAO plasma levels in patients with CKD undergoing hemodialysis.

Methods: Twenty-five patients were enrolled in the study (15 women, 53 (18) years, BMI, 25.8 (6.75) kg/m²). TMAO plasma levels were evaluated using the HPLC-EM/EM method. Fecal DNA was extracted using a commercial kit. Subsequently, we sequenced the V4 region of the 16S rRNA gene to characterize the microbial composition. NCT04600258 was retrospectively registered in September 2022.

Results: According to the reference values in the European Uremic Toxins Work Group (EUTox) database, the patients exhibited high TMAO plasma levels, as expected. The most abundant Archaea members were assigned to the Euryarchaeota phylum, the Methanobacteriaceae family, and the genus Methanobrevibacter. A significant negative correlation between TMAO and Methanobrevibacter was observed.

Conclusions: To our knowledge, this study represents the first investigation into the correlation between TMAO levels and the prevalence of Archaea in patients with CKD. Our findings support the archaebiotic hypothesis, suggesting that specific members of the archaea community could play a crucial role in reducing TMA production in the human gut, potentially decreasing TMAO synthesis in CKD patients.

Keywords: Archaea; Chronic kidney disease; Hemodialysis; Trimethylamine N-oxide.