Journal Article

Outgrowth of Escherichia is susceptible to aggravation of systemic lupus erythematosus

Wang, Mingbang, Zhang, Xi, Chen, Zena, Cui, Chunping, Zhang, Pingping, Guo, Xinghua, Lin, Zhiming, Feng, Junmei, Zhang, Yanli, Pathak, Janak L., Qi, Jun, Gu, Jieruo, Gui, Lian, Chen, Zhuanggui, Sun, Yuhan, Lv, Qing, Zhang, Yan, Zuo, Xiaoyu

2024

Overview

Background Systemic lupus erythematosus (SLE) is linked to host gut dysbiosis. Here we performed faecal gut microbiome sequencing to investigate SLE-pathogenic gut microbes and their potential mechanisms. Methods There were 134 healthy controls (HCs) and 114 SLE cases for 16 S ribosomal RNA (rRNA) sequencing and 97 HCs and 124 SLE cases for shotgun metagenomics. Faecal microbial changes and associations with clinical phenotypes were evaluated, and SLE-associated microbial genera were identified in amplicon analysis. Next, metagenomic sequencing was applied for accurate identification of microbial species and discovery of their metabolic pathways and immunogenic peptides both relevant to SLE. Finally, contribution of specific taxa to disease development was confirmed by oral gavage into lupus-prone MRL/ lpr mice. Results SLE patients had gut microbiota richness reduction and composition alteration, particularly lupus nephritis and active patients. Proteobacteria / Bacteroidetes (P/B) ratio was remarkably up-regulated, and Escherichia was identified as the dominantly expanded genus in SLE, followed by metagenomics accurately located Escherichia coli and Escherichia unclassified species. Significant associations primarily appeared among Escherichia coli , metabolic pathways of purine nucleotide salvage or peptidoglycan maturation and SLE disease activity index (SLEDAI), and between multiple epitopes from Escherichia coli and disease activity or renal involvement phenotype. Finally, gavage with faecal Escherichia revealed that it upregulated lupus-associated serum traits and aggravated glomerular lesions in MRL/ lpr mice. Conclusion We characterize a novel SLE exacerbating Escherichia outgrowth and suggest its contribution to SLE procession may be partially associated with metabolite changes and cross-reactivity of gut microbiota-associated epitopes and host autoantigens. The findings could provide a deeper insight into gut Escherichia in the procession of SLE.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Analysis / Animals / Antigenic determinants / Autoantigens / Autoimmunity / Bacteria, Pathogenic / Complications and side effects / Development and progression / Dysbiosis / Dysbiosis - immunology / Dysbiosis - microbiology / Enterobacter / Enterobacteriaceae / Escherichia / Escherichia coli / Escherichia coli - genetics / Escherichia coli - immunology / Feces - microbiology / Female / Gastrointestinal Microbiome - immunology / Gastrointestinal Microbiome - physiology / Gut microbiota dysbiosis / Gut microbiota-associated epitopes / Humans / Identification and classification / Immune response / Lupus / Lupus Erythematosus, Systemic - immunology / Lupus Erythematosus, Systemic - metabolism / Lupus Erythematosus, Systemic - microbiology / Male / Medicine / Medicine & Public Health / Metabolites / Metagenomics - methods / Mice / Mice, Inbred MRL lpr / Microbiota (Symbiotic organisms) / Middle Aged / Orthopedics / Physiological aspects / Rheumatology / Ribosomal RNA / Risk factors / Shotgun metagenomics / Somatotropin / Systemic lupus erythematosus