The Bladder Microbiome, Metabolome, Cytokines, and Phenotypes in Patients with Systemic Lupus Erythematosus

Abstract

ABSTRACT Emerging studies reveal unique bacterial communities in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles. We recruited a group of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and liquid chromatography-tandem mass spectrometry to perform untargeted metabolomic profiling. Compared to controls, SLE patients possessed unique bladder microbial communities and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients’ disease profiles. The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including olopatadine. The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including interleukin-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement component 3, and Streptococcus was positively correlated with IgG. Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE. IMPORTANCE Contrary to dogma, the human urinary bladder possesses its own unique bacterial community with alteration of composition associated with disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease often characterized by kidney impairment. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between the microbiome and metabolome, cytokines, and disease profiles. Compared to controls, SLE patients possessed a unique bladder microbial community and elevated alpha diversity. These differences were accompanied by differences in bladder metabolomes, cytokines, and patients’ disease profiles. SLE-enriched genera were positively correlated with several SLE-enriched metabolites. SLE-depleted genera were negatively correlated to SLE-depleted cytokines. Alteration of the bladder microbiome was associated with disease profile. Thus, our study reveals associations between the bladder microbiome and the bladder metabolome, cytokines, and disease phenotypes. These results could help identify biomarkers for SLE.

Keywords

• bladder microbiome
• complement
• disease profile
• systemic lupus erythematosus
• urinary cytokines
• urinary metabolome