Dysbiotic Oral and Gut Viromes in Untreated and Treated Rheumatoid Arthritis Patients

Guo, Ruochun; Li, Shenghui; Zhang, Yue; Wang, Guangyang; Ullah, Hayan; Ma, Yufang; Yan, Qiulong

doi:10.1128/spectrum.00348-22

Cited by 23 publications

(15 citation statements)

References 67 publications

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“…Notably, 19,844 of 67,096 vOTUs accounted for 99% of mapping reads across all samples ( Figure 1B ) and were further used to characterize the gut viral composition of the two cohorts. Similar to previous studies ( 30 , 31 ), the dominant families in the gut viral composition included Siphoviridae (mean relative abundance, 13.7%), Myoviridae (6.4%), Quimbyviridae (6.1%), and crAss-like viruses (1.4%), in addition to unclassified viruses ( Figure 1C ).…”

Section: Resultssupporting

confidence: 86%

Alterations in the gut virome in patients with ankylosing spondylitis

Zhang

Yan

et al. 2023

Front. Immunol.

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IntroductionAnkylosing spondylitis (AS), a chronic autoimmune disease, has been linked to the gut bacteriome.MethodsTo investigate the characteristics of the gut virome in AS, we profiled the gut viral community of 193 AS patients and 59 healthy subjects based on a metagenome-wide analysis of fecal metagenomes from two publicly available datasets.ResultsAS patients revealed a significant decrease in gut viral richness and a considerable alteration of the overall viral structure. At the family level, AS patients had an increased abundance of Gratiaviridae and Quimbyviridae and a decreased abundance of Drexlerviridae and Schitoviridae. We identified 1,004 differentially abundant viral operational taxonomic units (vOTUs) between patients and controls, including a higher proportion of AS-enriched Myoviridae viruses and control-enriched Siphoviridae viruses. Moreover, the AS-enriched vOTUs were more likely to infect bacteria such as Flavonifractor, Achromobacter, and Eggerthellaceae, whereas the control-enriched vOTUs were more likely to be Blautia, Ruminococcus, Collinsella, Prevotella, and Faecalibacterium bacteriophages. Additionally, some viral functional orthologs differed significantly in frequency between the AS-enriched and control-enriched vOTUs, suggesting the functional role of these AS-associated viruses. Moreover, we trained classification models based on gut viral signatures to discriminate AS patients from healthy controls, with an optimal area under the receiver operator characteristic curve (AUC) up to 0.936, suggesting the clinical potential of the gut virome for diagnosing AS.DiscussionThis work provides novel insight into the AS gut virome, and the findings may guide future mechanistic and therapeutic studies for other autoimmune diseases.

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Section: Resultssupporting

confidence: 86%

Alterations in the gut virome in patients with ankylosing spondylitis

Zhang

Yan

et al. 2023

Front. Immunol.

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“…reported enrichment of Lactococcus phages in the dental plaques of treated patients with RA as compared to untreated RA. However, minor changes in the gut virome were observed along with a significantly decreased abundance of the family Phycodnaviridae in treated patients with RA ( 45 ). As the role of the bacteriome in autoimmunity development has been well-established ( 46 ), the changes of bacteriophage abundance in at-risk individuals suggests that they might be involved in RA pathogenesis, perhaps by modulating bacterial taxa or by directly interacting with the host immune system.…”

Section: Gut Microbial Dysbiosis In Ramentioning

confidence: 99%

“…Thus, the symbiotic relationship of Faecalibacterium and Podoviridae could be important to maintain immune homeostasis. Another study has reported that the bacteria-virus interaction network is disrupted in treated patients with RA compared to untreated patients and healthy controls ( 45 ). Moreover, phages can affect gut bacteria pathogenicity by altering their adhesion, invasion, colonization, and toxin production ( 53 ).…”

Section: Crosstalk Between the Bacteriome Mycobiome And Viromementioning

confidence: 99%

Gut bacteriome, mycobiome and virome alterations in rheumatoid arthritis

et al. 2023

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Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease of the joints which causes significant pain, functional disability, and mortality. Although aberrant immune cell activation induced by the imbalance between T helper Th1/Th17 and Treg cells is implicated in the RA development, its etiopathogenesis remains unclear. The presence of mucosal inflammation and systemic IgA-isotype-autoantibodies (anti-citrullinated peptide antibodies and rheumatoid factor) in pre-clinical RA supports the mucosal origin hypothesis involving altered microbiota in disease development. The gut microbiota comprises diverse bacteria, fungal and viral components, which are critical in developing host immunity. Alterations in microbial abundance are known to exacerbate or attenuate immune responses in the gut microenvironment subsequently affecting the joints. Further, these changes can provide biomarkers for disease activity and outcome in RA. Most of the research till date has been focused on describing gut bacterial components in RA. Studies on gut mycobiome and virome components in RA are relatively new and burgeoning field. Given the paucity of mycobiome or virome specific studies in RA, this review, discusses the recent findings on alterations in gut bacterial, fungal, and viral components as well as their role in regulating the spectrum of immune-pathogenic events occurring in RA which might be explored in future as a potential therapeutic target. Further, we provide an overview on inter-kingdom interactions between bacteria, fungi, and viruses in RA. The current understanding on gut microbiota modulation for managing RA is also summarised.

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“…One additional limitation applies to phage therapeutics in a microbiome setting, namely the vital emerging roles of non-bacterial drivers of dysbiosis. These include viruses other than phages, which are increasingly recognized as important in maintaining gut ecological balance and contributors to dysbiosis in disease [ 109 , 110 , 111 , 112 ], as well as fungi and protozoa [ 113 , 114 , 115 , 116 , 117 ]. Phages targeting bacteria exclusively are unable to directly affect these organisms of emerging importance.…”

Section: Targeted Microbiome Therapeutics: Opportunities and Challengesmentioning

confidence: 99%

A Taxonomy-Agnostic Approach to Targeted Microbiome Therapeutics—Leveraging Principles of Systems Biology

et al. 2023

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The study of human microbiomes has yielded insights into basic science, and applied therapeutics are emerging. However, conflicting definitions of what microbiomes are and how they affect the health of the “host” are less understood. A major impediment towards systematic design, discovery, and implementation of targeted microbiome therapeutics is the continued reliance on taxonomic indicators to define microbiomes in health and disease. Such reliance often confounds analyses, potentially suggesting associations where there are none, and conversely failing to identify significant, causal relationships. This review article discusses recent discoveries pointing towards a molecular understanding of microbiome “dysbiosis” and away from a purely taxonomic approach. We highlight the growing role of systems biological principles in the complex interrelationships between the gut microbiome and host cells, and review current approaches commonly used in targeted microbiome therapeutics, including fecal microbial transplant, bacteriophage therapies, and the use of metabolic toxins to selectively eliminate specific taxa from dysbiotic microbiomes. These approaches, however, remain wholly or partially dependent on the bacterial taxa involved in dysbiosis, and therefore may not capitalize fully on many therapeutic opportunities presented at the bioactive molecular level. New technologies capable of addressing microbiome-associated diseases as molecular problems, if solved, will open possibilities of new classes and categories of targeted microbiome therapeutics aimed, in principle, at all dysbiosis-driven disorders.

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Dysbiotic Oral and Gut Viromes in Untreated and Treated Rheumatoid Arthritis Patients

Cited by 23 publications

References 67 publications

Alterations in the gut virome in patients with ankylosing spondylitis

Alterations in the gut virome in patients with ankylosing spondylitis

Gut bacteriome, mycobiome and virome alterations in rheumatoid arthritis

A Taxonomy-Agnostic Approach to Targeted Microbiome Therapeutics—Leveraging Principles of Systems Biology

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