Alterations of the gut virome in patients with systemic lupus erythematosus

Abstract

BackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease that has been linked to the dysbiosis of the gut microbiome and virome. However, the potential characterization of the gut virome in SLE patients needs to be explored more extensively.MethodsHerein, we analyzed the gut viral community of 16 SLE patients and 31 healthy controls using both bulk and virus-like particle (VLP)-based metagenomic sequencing of their fecal samples. A total of 15,999 non-redundant viral operational taxonomic units (vOTUs) were identified from the metagenomic assembled contigs and used for gut virome profiling.ResultsSLE patients exhibited a significant decrease in gut viral diversity in the bulk metagenome dataset, but this change was not significant in the VLP metagenome dataset. Also, considerable alterations of the overall gut virome composition and remarkable changes in the viral family compositions were observed in SLE patients compared with healthy controls, as observed in both two technologies. We identified 408 vOTUs (177 SLE-enriched and 231 control-enriched) with significantly different relative abundances between patients and controls in the bulk virome, and 18 vOTUs (17 SLE-enriched in 1 control-enriched) in the VLP virome. The SLE-enriched vOTUs included numerous Siphoviridae, Microviridae, and crAss-like viruses and were frequently predicted to infect Bacteroides, Parabacteroides, and Ruminococcus_E, while the control-enriched contained numerous members of Siphoviridae and Myoviridae and were predicted to infect Prevotella and Lachnospirales_CAG-274. We explored the correlations between gut viruses and bacteria and found that some Lachnospirales_CAG-274 and Hungatella_A phages may play key roles in the virus-bacterium network. Furthermore, we explored the gut viral signatures for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of above 0.95, suggesting the potential of the gut virome in the prediction of SLE.ConclusionOur findings demonstrated the alterations in viral diversity and taxonomic composition of the gut virome of SLE patients. Further research into the etiology of SLE and the gut viral community will open up new avenues for treating and preventing SLE and other autoimmune diseases.

Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology

“…On the other hand, in a seasonally anoxic freshwater lake, viromes were richer in viruses than metagenomes [6] but the magnitude of this difference was much smaller than that of the soil study. Viruses from the freshwater lake also primarily grouped by sample type (viromes or metagenomes) [6], while viruses assembled from viromes and metagenomes of human gut communities largely grouped by the disease status of the human host, rather than sample method [33]. These studies individually offer novel insights into the viral and prokaryotic community composition of their respective ecosystems, but they remain to be synthesized together into a broader context of method application.…”

Microbiome dynamics in rheumatic diseases

“…Interestingly, VLPs from SLE patients after treatment displayed a weakened interferon stimulation [29 ▪ ]. In another study involving metagenomic sequencing on stool samples from SLE patients and healthy controls, a significant reduction in enterovirus diversity was observed in SLE patients [30].…”

“…1). Notably, butyric acid exhibits specific interactions with various immune cells, including dendritic cells, macrophages, B cells, and more [30]. Supplementation with butyric acid has demonstrated the ability to mitigate the lupus phenotype in mice [38 ▪▪ ].…”

Virome in immunodeficiency: what we know currently

“…A significant reduction in Podoviridae was also observed in another SLE cohort. [64] Virome studies on other autoimmune diseases are limited. OA is a degenerative disease with synovial inflammation and articular margin hyperplasia.…”