Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(668)

Published: Oct. 26, 2022

The mucosal origins hypothesis of rheumatoid arthritis (RA) proposes a central role for immune responses in the initiation or perpetuation systemic autoimmunity that occurs with disease. However, connection between mucosa and RA remains unclear. Using dual immunoglobulin A (IgA) IgG family plasmablast–derived monoclonal autoantibodies obtained from peripheral blood individuals at risk RA, we identified cross-reactivity RA-relevant autoantigens bacterial taxa closely related families Lachnospiraceae Ruminococcaceae . After generating isolates within Lachnospiraceae/Ruminococcaceae genus Subdoligranulum feces an individual, confirmed antibody binding CD4 + T cell activation compared to control individuals. In addition, when isolate 7 but not 1 colonized germ-free mice, it stimulated H 17 expansion, serum RA–relevant autoantibodies, joint swelling reminiscent early histopathology characterized by deposition complement activation. Systemic were likely due invasion along generation colon-isolated lymphoid follicles driving increased fecal IgA 7, because B depletion only halted intestinal also eliminated detectable clinical aggregate, these findings demonstrate mechanism pathogenesis through which specific strain bacteria can drive autoantibody joint-centered

Language: Английский

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Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression

Journal of Autoimmunity, Journal Year: 2023, Volume and Issue: 141, P. 103001 - 103001

Published: March 15, 2023

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA prolonged state before clinical develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due the breakdown of immunologic self-tolerance. As early treatment initiation onset may achieve sustained remission, optimize outcomes, even prevent progression, pre-clinical stage showing prospect window opportunity for treatment. Growing evidence has shown role gut microbiota inducing systemic inflammation via multiple mechanisms, involve molecular mimicry, impaired intestinal barrier function, microbiota-derived metabolites mediated immune regulation, modulation microbiota's effect on cells, epithelial cells autophagy, interaction between microbiome human leukocyte antigen alleles as well microRNAs. Since alterations have been reported, potential therapies modifying RA, including natural products, antibiotic therapy, fecal transplantation, probiotics, microRNAs vitamin D supplementation, autophagy inducer-based treatment, prebiotics, diet, holds great promise successful prevention altering ongoing inflammation. In this review, we summarized current studies include pathogenesis progression promising therapeutic strategies provide novel ideas management possibly preventing progression.

Language: Английский

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Ecological and functional roles of bacteriophages in contrasting environments: marine, terrestrial and human gut

Current Opinion in Microbiology, Journal Year: 2022, Volume and Issue: 70, P. 102229 - 102229

Published: Nov. 5, 2022

While they are the most abundant biological entities on planet, role of bacteriophages (phages) in microbiome remains enigmatic and understudied. With a rise number metagenomics studies publication highly efficient phage mining programmes, we now have extensive data genomic taxonomic diversity (mainly) DNA wide range environments. In addition, higher throughput quality sequencing is allowing for strain-level reconstructions genomes from metagenomes. These factors will ultimately help us to understand these phages play as part specific microbial communities, enabling tracking individual virus through space time. Using lessons learned latest metagenomic studies, focus two explicit aspects within microbiome, their ecological structuring bacterial populations, contribution functioning by encoding auxiliary metabolism genes.

Language: Английский

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Intestinal phages interact with bacteria and are involved in human diseases

Gut Microbes, Journal Year: 2022, Volume and Issue: 14(1)

Published: Aug. 29, 2022

Phages are the most abundant and diverse biological entities on Earth exert specific effects bacterial hosts. The coexistence of phages bacteria in intestinal tract is dynamic interdependent. involved maintaining stability composition community, an imbalance can cause diseases. This review elucidates interactions between human their roles pathogenesis treatment Understanding relationship among phages, host diseases conducive to promoting application diseases.List abbreviations EMBL-EBI European Bioinformatics Institute; E. coli Escherichia coli; faecalis Enterobacter faecalis; B. fragilis Bacteroides fragilis; vulgatus vulgatus; SaPIs Staphylococcus aureus pathogenicity islands; ARGs Antibiotic resistance genes; STEC Shiga toxigenic Stx toxin; BLAST Basic Local Alignment Search Tool; TSST-1 Toxic shock toxin 1; RBPs Receptor-binding proteins; LPS lipopolysaccharide; OMVs Outer membrane vesicles; PT Phosphorothioate; BREX Bacteriophage exclusion; OCR Overcome classical restriction; Pgl Phage growth limitation; DISARM Defense island system associated with restrictionmodification; R-M Restriction-modification system; exclusion CRISPR Clustered regularly interspaced short palindromic repeats; Cas CRISPR-associated; PAMs Prospacer adjacent motifs; crRNA RNA; SIE; OMPs; Superinfection Abi Abortive infection; TA Toxin-antitoxin; TLR Toll-like receptor; APCs Antigen-presenting cells; DSS Dextran sulfate sodium; IELs Intraepithelial lymphocytes; FMT Fecal microbiota transfer; IFN-γ Interferon-gamma; IBD Inflammatory bowel disease; AgNPs Silver nanoparticles; MDSC Myeloid-derived suppressor cell; CRC Colorectal cancer; VLPs Virus-like particles; TMP Tape measure protein; PSMB4 Proteasome subunit beta type-4; ALD Alcohol-related liver GVHD Graft-versus-host ROS Reactive oxygen species; RA Rheumatoid arthritis; CCP Cyclic citrullinated AMGs Accessory metabolic T1DM Type 1 diabetes mellitus; T2DM 2 SCFAs Short-chain fatty acids; GLP-1 Glucagon-like peptide-1; A. baumannii Acinetobacter baumannii; CpG Deoxycytidylinate-phosphodeoxyguanosine; PEG Polyethylene glycol; MetS Metabolic syndrome; OprM porin M.

Language: Английский

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Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis

Microbiome, Journal Year: 2022, Volume and Issue: 10(1)

Published: July 8, 2022

Abstract Background Inflammatory bowel diseases (IBDs) including Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by chronic debilitating gut inflammation. Altered bacterial communities of the intestine strongly associated with IBD initiation progression. The virome, which is primarily composed viruses (bacteriophages, phages), thought to be an important factor regulating shaping microbial in gut. While alterations virome have been observed patients, contribution these community heightened inflammatory responses patients remains largely unknown. Results Here, we performed vivo cross-infection experiments follow effects fecal virus-like particles (VLPs) isolated from UC healthy controls on diversity severity experimental human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred HMA mice, resulting treatment-specific virome. VLPs also shifted effect was amplified during colitis. specifically altered relative abundance taxa previously implicated Additionally, VLP administration as indicated shortened colon length increased pro-inflammatory cytokine production. Importantly, this dependent intact VLPs. Conclusions Our findings build recent literature indicating dynamic regulators implicate intestinal modulating inflammation disease.

Language: Английский

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Benzo[a]pyrene stress impacts adaptive strategies and ecological functions of earthworm intestinal viromes

The ISME Journal, Journal Year: 2023, Volume and Issue: 17(7), P. 1004 - 1014

Published: April 17, 2023

The earthworm gut virome influences the structure and function of microbiome, which in turn worm health ecological functions. However, despite its soil quality implications, it remains elusive how intestinal phages respond to different environmental stress, such as pollution. Here we used metagenomics metatranscriptomics investigate interactions between their bacteria under benzo[a]pyrene (BaP) concentrations. Low-level BaP (0.1 mg kg-1) stress stimulated microbial metabolism (1.74-fold control), enhanced antiphage defense system (n = 75) against infection (8 phage-host pairs). exposure resulted highest proportion lysogenic (88%), prophages expressed auxiliary metabolic genes (AMGs) associated with nutrient transformation (e.g., amino acid metabolism). In contrast, high-level (200 disrupted suppressed systems 29), leading increase phage-bacterium association (37 pairs) conversion lytic (lysogenic ratio declined 43%). Despite fluctuating interactions, phage-encoded AMGs related antioxidant pollutant degradation were enriched, apparently alleviate pollution stress. Overall, these findings expand our knowledge complex pollution-stressed guts, deepen understanding evolutionary roles phages.

Language: Английский

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Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis

Nature Reviews Rheumatology, Journal Year: 2024, Volume and Issue: 20(10), P. 601 - 613

Published: Sept. 9, 2024

Language: Английский

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Rheumatoid arthritis and the intestinal microbiome: probiotics as a potential therapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 6, 2024

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by swollen joints, discomfort, stiffness, osteoporosis, and reduced functionality. Genetics, smoking, dust inhalation, high BMI, hormonal gut microbiota dysbiosis are all likely causes of the onset or development RA, but underlying mechanism remains unknown. Compared to healthy controls, patients with RA have significantly different composition microbiota. It well known that human plays key role in initiation, maintenance, operation host immune system. Gut has local systematic adverse effects on system, resulting susceptibility various diseases, including RA. Studies intestinal modulation immunomodulatory properties probiotics been reported, order identify their potential possibility prevention disease activity control This review summarized current studies mechanisms progression as preventative therapeutic Additionally, we proposed challenges difficulties application providing direction for research

Language: Английский

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Efficient Recovery of Complete Gut Viral Genomes by Combined Short‐ and Long‐Read Sequencing

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 19, 2024

Abstract Current metagenome assembled human gut phage catalogs contained mostly fragmented genomes. Here, comprehensive virome detection procedure is developed involving virus‐like particle (VLP) enrichment from ≈500 g feces and combined sequencing of short‐ long‐read. Applied to 135 samples, a Chinese Gut Virome Catalog (CHGV) consisting 21,499 non‐redundant viral operational taxonomic units (vOTUs) that are significantly longer than those obtained by short‐read ≈35% (7675) complete genomes, which ≈nine times more in the Database (GVD, ≈4%, 1,443). Interestingly, majority (≈60%, 13,356) CHGV vOTUs either long‐read or hybrid assemblies, with little overlap only data. With this dataset, vast diversity elucidated, including identification 32% (6,962) novel compare public databases, dozens phages prevalent crAssphages and/or Gubaphages, several clades diverse two. Finally, functional capacities also characterized encoded proteins constructed viral‐host interaction network facilitate future research applications.

Language: Английский

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Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease

Annals of the Rheumatic Diseases, Journal Year: 2021, Volume and Issue: 81(2), P. 278 - 288

Published: Dec. 8, 2021

Objective The relationship between autoimmune diseases and the gut microbiome has been intensively studied, several autoimmunity-associated bacterial taxa have identified. However, much less is known about roles of virome in diseases. Methods Here, we performed a whole analysis based on shotgun sequencing 476 Japanese which included patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis healthy control subjects. Results Our case–control comparison viral abundance revealed that crAss-like phages, are one main components virome, significantly decreased disease, specifically RA SLE. In addition, Podoviridae To understand how these viruses affected bacteriome, quantitative virus–bacterium association clustered regularly interspaced short palindromic repeat-based interaction analysis. We identified symbiosis Podovirida e Faecalibacterium . targets phages were (eg, Ruminococcus spp). Conclusion data suggest can affect our body either directly or via bacteria. analyses elucidated previously missing part presented new candidates contribute to development

Language: Английский

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