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BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.
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Artrite Gotosa , Microbioma Gastrointestinal , Osteoartrite , Viroma , Humanos , Artrite Gotosa/virologia , Artrite Gotosa/microbiologia , Masculino , Osteoartrite/virologia , Osteoartrite/microbiologia , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Metagenômica , Fezes/virologia , Fezes/microbiologiaRESUMO
BACKGROUND: The contribution of gut microbiota to human high-altitude adaptation remains inadequately understood. METHODS: Here a comparative analysis of gut microbiota was conducted between healthy individuals living at sea level and high altitude using deep whole-metagenome shotgun sequencing, to investigate the adaptive mechanisms of gut microbiota in plateau inhabitants. RESULTS: The results showed the gut bacteriomes in high-altitude individuals exhibited greater within-sample diversity and significant alterations in both bacterial compositional and functional profiles when compared to those of sea-level individuals, indicating the potential selection of unique bacteria associated with high-altitude environments. The strain-level investigation revealed enrichment of Collinsella aerofaciens and Akkermansia muciniphila in high-altitude populations. The characteristics of gut virome and gut mycobiome were also investigated. Compared to sea-level subjects, high-altitude subjects exhibited a greater diversity in their gut virome, with an increased number of viral operational taxonomic units (vOTUs) and unique annotated genes. Finally, correlation analyses revealed 819 significant correlations between 42 bacterial species and 375 vOTUs, while no significant correlations were observed between bacteria and fungi or between fungi and viruses. CONCLUSION: The findings have significantly contributed to an enhanced comprehension of the mechanisms underlying the high-altitude geographic adaptation of the human gut microbiota.
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OBJECTIVE: The gut microbial composition has been linked to metabolic and autoimmune diseases, including arthritis. However, there is a dearth of knowledge on the gut bacteriome, mycobiome, and virome in patients with gouty arthritis (GA). METHODS: We conducted a comprehensive analysis of the multi-kingdom gut microbiome of 26 GA patients and 28 healthy controls, using whole-metagenome shotgun sequencing of their stool samples. RESULTS: Profound alterations were observed in the gut bacteriome, mycobiome, and virome of GA patients. We identified 1,117 differentially abundant bacterial species, 23 fungal species, and 4,115 viral operational taxonomic units (vOTUs). GA-enriched bacteria included Escherichia coli_D GENOME144544, Bifidobacterium infantis GENOME095938, Blautia_A wexlerae GENOME096067, and Klebsiella pneumoniae GENOME147598, while control-enriched bacteria comprised Faecalibacterium prausnitzii_G GENOME147678, Agathobacter rectalis GENOME143712, and Bacteroides_A plebeius_A GENOME239725. GA-enriched fungi included opportunistic pathogens like Cryptococcus neoformans GCA_011057565, Candida parapsilosis GCA_000182765, and Malassezia spp., while control-enriched fungi featured several Hortaea werneckii subclades and Aspergillus fumigatus GCA_000002655. GA-enriched vOTUs mainly attributed to Siphoviridae, Myoviridae, Podoviridae, and Microviridae, whereas control-enriched vOTUs spanned 13 families, including Siphoviridae, Myoviridae, Podoviridae, Quimbyviridae, Phycodnaviridae, and crAss-like. A co-abundance network revealed intricate interactions among these multi-kingdom signatures, signifying their collective influence on the disease. Furthermore, these microbial signatures demonstrated the potential to effectively discriminate between patients and controls, highlighting their diagnostic utility. CONCLUSIONS: This study yields crucial insights into the characteristics of the GA microbiota that may inform future mechanistic and therapeutic investigations.
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Artrite Gotosa , Microbioma Gastrointestinal , Microbiota , Micobioma , Humanos , População do Leste Asiático , Bactérias/genéticaRESUMO
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and axonopathy is its main pathological feature. Previous studies suggested an advantage of taurine against diabetes. However, there are few reports which study the effect of taurine against axonopathy. In this study, we confirmed that taurine significantly decreased blood glucose level, mitigated insulin resistance and improved dysfunctional nerve conduction in diabetic rats. Taurine corrected damaged axonal morphology of sciatic nerve in diabetic rats and induced axon outgrowth of Dorsal root ganglion (DRG) neurons exposed to high glucose. Taurine up-regulated phosphorylation levels of PI3K, Akt, and mTOR in sciatic nerve of diabetic rats and DRG neurons exposed to high glucose. However, Akt and mTOR inhibitors (MK-2206 and Rapamycin) blocked the effect of taurine on improving axonal damage. These results indicate that taurine ameliorates axonal damage in sciatic nerve of diabetic rats by activating PI3K/Akt/mTOR signal pathway. Our findings provide taurine as a potential candidate for axonopathy and a new evidence for elucidating protective mechanism of taurine on DPN.
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Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Gânglios Espinais/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Taurina/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Gânglios Espinais/crescimento & desenvolvimento , Gânglios Espinais/metabolismo , Resistência à Insulina , Condução Nervosa/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Nervo Isquiático/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Tuberculosis (TB) causes millions of deaths each year across the globe. Multiple drug-resistant (MDR) and extensively drug-resistant (XDR) mycobacterial strains have made the treatment extremely difficult. To overcome this hurdle, the development of new drug targets and an effective treatment strategy are desperately needed. This can be achieved by deciphering the role of essential genes and enzymes which are involved in cell survival. One such enzyme is glyoxalase II. The glyoxalase system (glyoxalase I and glyoxalase II) has a pivotal role in cellular survival and detoxification by converting methylglyoxal (MG) into lactate. Otherwise, the increased concentration of MG then modifies DNA, proteins, and lipids, resulting in abnormalities and cell death. Interestingly, the function and physiological role of glyoxalase II have remained undetermined in mycobacteria. In this study, the functional activity of MSMEG_2975 (putative glyoxalase II) after heterologous cloning and expression was determined. And the knockdown strain Mycobacterium smegmatis KD for MSMEG_2975 was constructed with tetracycline-inducible vector pMIND. The inducible knockdown of MSMEG_2975 affected bacterial growth, biofilm formation, transcriptome, and enhanced the susceptibility to antibiotics. This work represents mycobacterial glyoxalase II as a potential drug target against mycobacterial pathogens and indicates the crucial regulatory role of glyoxalase II in mycobacteria.
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Mycobacterium smegmatis , Transcriptoma , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes , Mycobacterium smegmatis/genética , Tioléster HidrolasesRESUMO
Hyperuricemia is a prevalent metabolic disorder that arises from abnormal purine metabolism and reduced excretion of uric acid (UA). The gut microbiota plays a significant role in the biosynthesis and excretion of UA. Probiotics capable of purine degradation possess the potential to prevent hyperuricemia. Our study aimed to screen probiotics in areas with abundant dairy products and longevity populations in China, which could attenuate the level of UA and explore the underlying mechanism. In this study, twenty-three lactic acid bacteria isolated from healthy Chinese infant feces and traditional fermented foods such as hurood and lump milk were evaluated for the ability to tolerance acid, bile, artificial gastric juice, and artificial intestinal juice to determine the potential of the candidate strains as probiotics. Eight strains were identified as possessing superior tolerance to simulated intestinal conditions and were further analyzed by high-performance liquid chromatography (HPLC), revealing that Limosilactobacillus reuteri HCS02-001 (Lact-1) and Lacticaseibacillus paracasei HCS17-040 (Lact-2) possess the most potent ability to degrade purine nucleosides. The effect of Lact-1 and Lact-2 on hyperuricemia was evaluated by intervening with them in the potassium oxonate and adenine-induced hyperuricemia Balb/c mice model in vivo. Our results showed that the level of serum UA in hyperuricemic mice can be efficiently reduced via the oral administration of Lact-1 (p < 0.05). It significantly inhibited the levels of liver inflammatory cytokines and hepatic xanthine oxidase through a TLR4/MyD88/NF-κB pathway across the gut-liver axis. Furthermore, UA transporters ABCG2 and SLC2A9 were substantially upregulated by the intervention of this probiotic. Fecal ATP levels were significantly induced, while fecal xanthine dehydrogenase and allantoinase levels were increased following probiotics. RNA sequencing of HT-29 cells line treated with Lact-1 and its metabolites demonstrated significant regulation of pathways related to hyperuricemia. In summary, these findings demonstrate that Limosilactobacillus reuteri HCS02-001 possesses a capacity to ameliorate hyperuricemia by inhibiting UA biosynthesis via enhancing gastrointestinal barrier functions and promoting UA removal through the upregulation of urate transporters, thereby providing a basis for the probiotic formulation by targeting the gut microbiota.
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Mycobacterium tuberculosis (Mtb) ranks as the most lethal human pathogen, able to fend off repeated attacks by the immune system or medications. PE_PGRS proteins are hallmarks of the pathogenicity of Mtb and contribute to its antigenic diversity, virulence, and persistence during infection. M. smegmatis is a nonpathogenic mycobacterium that naturally lacks PE_PGRS and is used as a model to express Mtb proteins. PE_PGRS has the capability to evade host immune responses and enhance the intracellular survival of M. smegmatis. Despite the intense investigations into PE_PGRS proteins, their role in tuberculosis remains elusive. We engineered the recombinant M. smegmatis strain Ms-PE_PGRS38. The result shows that PE_PGRS38 is expressed in the cell wall of M. smegmatis. PE_PGRS38 contributes to biofilm formation, confers permeability to the cell wall, and shows variable responses to exogenous stresses. PE_PGRS38 downregulated TLR4/NF-κB signaling in RAW264.7 macrophages and lung tissues of infected mice. In addition, PE_PGRS38 decreased NLRP3-dependent IL-1ß release and limited pathogen-mediated inflammasome activity during infection. Moreover, PE_PGRS38 inhibited the apoptosis of RAW264.7 cells by downregulating the expression of apoptotic markers including Bax, cytochrome c, caspase-3, and caspase-9. In a nutshell, our findings demonstrate that PE_PGRS38 is a virulence factor for Mtb that enables recombinant M. smegmatis to survive by resisting and evading the host's immune responses during infection.
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BACKGROUND: Rheumatoid arthritis, a condition characterized by inflammation, has a substantial influence on both the worldwide economy and public health. Prior studies indicate that probiotics have the potential to enhance the composition of gut microbiota in instances of intestinal dysbiosis resulting from different disorders and contribute to the regulation of inflammation. The objective of this study is to investigate the impact of Saccharomyces boulardii on the gut microbiome in arthritis and its implications on inflammation. METHODS: The study utilized the Collagen Induced Arthritis (CIA) Sprague-Dawley (SD) rat model. After administering Saccharomyces boulardii (150 mg/kg/day) six days a week and Methotrexate (MTX) (0.2 mg/week) treatment for eight weeks, microbial DNA from the feces was sequenced using 16S rRNA. The evaluation of histopathology, bone loss, and cartilage degradation was conducted using histology, immunohistology assays, and micro-computed tomography (µCT) examinations. The enzyme-linked immunosorbent assay (ELISA) was used to analyze proinflammatory cytokines, while the western blot technique was applied to detect protein in the gut and in cell lines. The quantification of gene expression in gut,joint and cell lines was performed using real-time polymerase chain reaction. The cell lines were activated and then treated with the culture supernatant of S. boulardii for an in vitro investigation. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was utilized to assess cell proliferationand viability. Cellular motility was measured in a wound healing experiment, whereas apoptotic proteins were analyzed using Western blotting. RESULTS: S. boulardii has been found to enhance bone and joint integrity, modulate gut microbiota, and mitigate proinflammatory cytokine levels in rats with arthritis. It decreases the permeability of the intestines and promotes the production of gut tight-junction proteins. The administration of S. boulardii inhibits the proliferation of T-helper-17 (Th17) and Type 3 innate lymphoid cells (ILC3). Additionally, it elicits apoptosis in MH7A cell lines and hinders their migratory activity. CONCLUSION: This study provides valuable insights into the therapeutic potential of S. boulardii for treating and preventing arthritis in rats with collagen-induced arthritis by modulating gut microbiota and inflammation.
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Artrite Experimental , Microbioma Gastrointestinal , Mucosa Intestinal , NF-kappa B , Probióticos , Ratos Sprague-Dawley , Saccharomyces boulardii , Transdução de Sinais , Receptor 2 Toll-Like , Animais , Artrite Experimental/imunologia , Artrite Experimental/terapia , Probióticos/uso terapêutico , NF-kappa B/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Ratos , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Humanos , Citocinas/metabolismo , Linhagem Celular , Artrite Reumatoide/terapia , Artrite Reumatoide/imunologia , Fator 88 de Diferenciação MieloideRESUMO
Mycobacterium tuberculosis (Mtb) is the pathogenic agent of tuberculosis (TB). Intracellular survival plays a central role in the pathogenesis of Mtb, a process that depends on an array of virulence factors for Mtb to colonize and proliferate within a host. Reactive nitrogen and oxygen species (RNS and ROS) are among the most effective antimycobacterial molecules generated by the host during infection. However, Mtb has evolved a number of proteins and enzymes to detoxify ROS and RNS. Secretory protein Rv1324, as a possible thioredoxin, might also have oxidoreductase activity against ROS and RNS during Mtb infection, and it is a potential virulence factor of Mtb. In this study, we investigated the biochemical properties of Mtb Rv1324 and its role in mycobacterial survival and virulence. The results showed that the Rv1324 protein had antioxidant activity and increased the survival of M. smegmatis that was exposed to ROS and RNS. In addition, Rv1324 enhanced the colonization ability of M. smegmatis in the lungs of mice. Further, mice infected with M. smegmatis harboring Rv1324 exhibited pathological injury and inflammation in the lung, which was mediated by ferroptosis. In summary, this study advances our understanding of the mechanisms of mycobacterial survival and pathogenesis, and it reveals a novel target for TB treatment. IMPORTANCE The intracellular survival of M. tuberculosis (Mtb) plays a crucial role in its pathogenesis, which depends on various Mtb oxidoreductases that are resistant to reactive oxygen and nitrogen species (ROS and RNS) that are generated by the host during Mtb infection. Secretory protein Rv1324 is a potential virulence factor of Mtb and is a possible thioredoxin that has oxidoreductase activity against ROS and RNS during Mtb infection. We investigated the biochemical properties of Mtb Rv1324 and its role in mycobacterial survival and virulence. It was confirmed that the Rv1324 protein had antioxidant activity and an increased mycobacterial resistance to ROS and RNS. In addition, Rv1324 enhanced mycobacterial persistence and induced pathological injury and inflammation in the lungs of mice by activating ferroptosis. This study advances our understanding of the mechanisms of mycobacterial survival and pathogenesis, and it reveals a novel target for TB treatment.
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Ferroptose , Lesão Pulmonar , Mycobacterium tuberculosis , Tuberculose , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Tuberculose/microbiologia , Oxirredutases/metabolismo , Fatores Imunológicos/farmacologia , Fatores de Virulência/metabolismo , Inflamação , Oxigênio/metabolismo , Tiorredoxinas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
INTRODUCTION: Viruses have been reported as inducers of tumorigenesis. Little studies have explored the impact of the gut virome on the progression of colorectal cancer. However, there is still a problem with the repeatability of viral signatures across multiple cohorts. OBJECTIVES: The present study aimed to reveal the repeatable gut vial signatures of colorectal cancer and adenoma patients and decipher the potential of viral markers in disease risk assessment for diagnosis. METHODS: 1,282 available fecal metagenomes from 9 published studies for colorectal cancer and adenoma were collected. A gut viral catalog was constructed via a reference-independent approach. Viral signatures were identified by cross-cohort meta-analysis and used to build predictive models based on machine learning algorithms. New fecal samples were collected to validate the generalization of predictive models. RESULTS: The gut viral composition of colorectal cancer patients was drastically altered compared with healthy, as evidenced by changes in some Siphoviridae and Myoviridae viruses and enrichment of Microviridae, whereas the virome variation in adenoma patients was relatively low. Cross-cohort meta-analysis identified 405 differential viruses for colorectal cancer, including several phages of Porphyromonas, Fusobacterium, and Hungatella that were enriched in patients and some control-enriched Ruminococcaceae phages. In 9 discovery cohorts, the optimal risk assessment model obtained an average cross-cohort area under the curve of 0.830 for discriminating colorectal cancer patients from controls. This model also showed consistently high accuracy in 2 independent validation cohorts (optimal area under the curve, 0.906). Gut virome analysis of adenoma patients identified 88 differential viruses and achieved an optimal area under the curve of 0.772 for discriminating patients from controls. CONCLUSION: Our findings demonstrate the gut virome characteristics in colorectal cancer and adenoma and highlight gut virus-bacterial synergy in the progression of colorectal cancer. The gut viral signatures may be new targets for colorectal cancer treatment. In addition, high repeatability and predictive power of the prediction models suggest the potential of gut viral biomarkers in non-invasive diagnostic tests of colorectal cancer and adenoma.
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Adenoma , Neoplasias Colorretais , Microbioma Gastrointestinal , Vírus , Humanos , Viroma , Adenoma/diagnóstico , Medição de Risco , Biomarcadores , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/microbiologiaRESUMO
Mycobacterium tuberculosis cell wall consist variety of mannose containing glycoconjugates including lipomannan (LM) and lipoarabinomannan (LAM). These lipoglycans are involved in cell wall integrity and play role in virulence of M. tuberculosis by modulating host immune response. GDP-mannose, required for the synthesis of lipoglycans, is catalyzed by enzyme Mannose-1-phosphate guanylyl transferase (ManB). The enzyme with similar function has been studied in variety of species of prokaryotes and eukaryotes. However, biological role of ManB and its enzymatic activity remains uncharacterized in M. tuberculosis. In present study, we elucidated the role of enzyme by constructing manB knockdown strain of M. tuberculosis H37Ra. The manB knockdown decreased the cell growth and also effected the morphology of M. tuberculosis by altering the permeability of cell membrane. These findings provide the understanding on ManB function and suggesting that ManB could be the potential target for novel anti-tuberculosis drug. Furthermore, we also characterized ManB enzyme by establishing 96 well plate colorimetric assay and determined the kinetic properties including initial velocity, optimum temperature, optimum pH and other kinetic parameters. Our established assay will be helpful for further high throughput screening of potential inhibitors against ManB.
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Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis , Nucleotidiltransferases/metabolismo , Parede Celular/metabolismo , Lipopolissacarídeos/metabolismo , Manose/metabolismo , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/genética , Fosfatos/metabolismo , Transferases/análise , Transferases/metabolismoRESUMO
Rheumatoid arthritis (RA) is influenced by oral and gut bacteria; however, much less is known about the relationship between oral or gut viromes and RA. Here, we performed whole-oral- and whole-gut-virome analyses based on shotgun sequencing of 497 samples. A comparative analysis of the oral and gut viromes in healthy controls and untreated and treated RA patients was performed, and system interaction networks among viruses, bacteria, and RA-associated clinical indices were constructed to address the potential relationship between the virome and RA by principal-coordinate analysis, distance-based redundancy analysis, permutational multivariate analysis, Spearman correlation coefficient analysis, and random-forest model analysis. The results showed that the viromes could be profiled in dental plaque, saliva, and fecal samples, among which saliva had the highest within-sample diversity. Importantly, significantly different diversities and compositions of the oral (i.e., dental plaque and saliva) viromes were observed not only between RA patients and healthy controls but also between untreated and treated RA patients, yet there were relatively minor differences in the gut viromes. Furthermore, to understand how these viruses affected the bacteriome, a virus-bacterium interaction network was constructed from dental plaque, saliva, and fecal samples of RA patients. Additionally, some RA-associated oral taxa, including Lactococcus phage (vOTU70), Bacteroides vulgatus, Lactococcus lactis, Escherichia coli, and Neisseria elongata, were correlated with the RA-related clinical indices. Whole-virome analysis illustrated the potential role of the oral and gut viromes in affecting our body either directly or via bacteria, which characterized neglected and new candidates contributing to the development of RA. IMPORTANCE Our results demonstrated community variation among dental plaque, saliva, and fecal viromes. In oral and gut samples from untreated and treated RA patients, the perturbance of viral composition and the correlation network of microbes and RA-associated clinical indices might be involved in the pathogenicity of RA. The findings in this study expand the knowledge of the potential role of oral and gut viral communities in the development of RA and may contribute to research on correlations between viruses and other diseases.
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Artrite Reumatoide , Placa Dentária , Vírus , Humanos , Viroma , Disbiose , Vírus/genética , Bactérias/genéticaRESUMO
Background: Systemic 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. Methods: Herein, 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. Results: SLE 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. Conclusion: Our 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.