Clinical significance of gut microbiota-derived metabolite trimethylamine N-oxide in patients with systemic lupus erythematosus

Abstract Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, is associated with cardiovascular disease (CVD) via pro-inflammatory and pro-atherogenic mechanisms. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a significantly increased risk of CVD, however, the role of TMAO in SLE remains unclear. This study aimed to assess the clinical significance of TMAO in patients with SLE, including analyses of precursor metabolites and gut microbiome. A total of 207 participants were enrolled, including 157 patients with SLE and 50 healthy controls. Serum TMAO levels were measured using ELISA, fecal precursor metabolites including trimethylamine (TMA) were quantified by 1 H-NMR spectroscopy, and gut microbiota composition was assessed using 16S rRNA sequencing. SLE patients with CVD had significantly higher TMAO levels than HC ( P = 0.028) and SLE patients without CVD ( P = 0.004). Serum TMAO ( P = 0.025) and fecal TMA ( P = 0.032) levels were positively correlated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum TMAO was negatively correlated with steroid dose ( P = 0.038). Distinct gut microbiota compositions were observed between SLE patients with and without CVD. TMAO is associated with cardiovascular disease and cumulative organ damage in SLE, potentially mediated by gut microbiome alterations and modulated by steroid therapy.