Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 477 - 477

Published: March 8, 2024

The gut mucosal epithelium is one of the largest organs in body and plays a critical role regulating crosstalk between resident microbiome host. To this effect, tight control what permitted through barrier high importance. There should be restricted passage harmful microorganisms antigens while at same time allowing absorption nutrients water. An increased permeability, or “leaky gut”, has been associated with variety diseases ranging from infections, metabolic diseases, inflammatory autoimmune to neurological conditions. Several factors can affect including cytokines, dietary components, microbiome. Here, we discuss how impacts permeability epithelial harnessed for therapeutic purposes.

Language: Английский

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Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 27, 2023

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by loss of immune tolerance and chronic inflammation. It pathogenesis complex includes interaction between genetic environmental factors. Current evidence supports the hypothesis that gut dysbiosis may play role triggers arthritis in animals humans. Progress understanding microbiome RA. has been remarkable last decade. In vitro vivo experiments revealed could shape system cause persistent inflammatory responses. Furthermore, induce alterations intestinal permeability, which have found to predate onset. contrast, metabolites derived from microbiota immunomodulatory anti-inflammatory effect. However, precise underlying mechanisms induces development remain elusive. This review aimed highlight contribute The overall data showed RA multiple pathways, including barrier function, molecular mimicry, influences activation differentiation innate acquired cells, cross-talk microbiota-derived microenvironment. relative weight each these remains uncertain. Recent studies a substantial for pathway, especially butyrate, pathogenesis.

Language: Английский

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Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares

Annals of the Rheumatic Diseases, Journal Year: 2023, Volume and Issue: 82(10), P. 1315 - 1327

Published: June 26, 2023

Objective Whereas genetic susceptibility for systemic lupus erythematosus (SLE) has been well explored, the triggers clinical disease flares remain elusive. To investigate relationships between microbiota community resilience and activity, we performed first longitudinal analyses of gut-microbiota communities. Methods In an observational study, taxononomic analyses, including multivariate analysis ß-diversity, assessed time-dependent alterations in faecal communities from patients healthy controls. From gut blooms, strains were isolated, with genomes associated glycans analysed. Results Multivariate documented that, unlike controls, significant temporal community-wide ecological instability was common SLE patients, transient intestinal growth spikes several pathogenic species documented. Expansions only anaerobic commensal, Ruminococcus (blautia) gnavus (RG) occurred at times high-disease detected almost half during nephritis (LN) flares. Whole genome sequence RG isolated these 34 genes postulated to aid adaptation expansion within a host inflammatory condition. Yet, most specific feature found expression novel type cell membrane-associated lipoglycan. These lipoglycans share conserved structural features by mass spectroscopy, highly immunogenic repetitive antigenic-determinants, recognised high-level serum IgG2 antibodies, that spontaneously arose, concurrent blooms Conclusions Our findings rationalise how pathobiont may be drivers often remitting-relapsing disease, highlight potential properties active LN patients.

Language: Английский

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Modifiable risk factors linked to the development of rheumatoid arthritis: evidence, immunological mechanisms and prevention

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 12, 2023

Rheumatoid Arthritis (RA) is a common autoimmune disease that targets the synovial joints leading to arthritis. Although etiology of RA remains largely unknown, it clear numerous modifiable risk factors confer increased developing RA. Of these factors, cigarette smoking, nutrition, obesity, occupational exposures and periodontal all incrementally increase risk. However, precise immunological mechanisms by which lead are not well understood. Basic translational studies have provided key insights into relationship between inflammation, antibody production influence in other cellular events such as T cell polarization Improving our general understanding will help identify for prevention trials, underway at-risk populations. Herein, we review linked development describe immune may be involved. We highlight few sought understand if modification reduces Finally, speculate an appealing avenue some individuals, specifically those who prefer lifestyle interventions due safety economic reasons.

Language: Английский

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Microbiota-dependent indole production stimulates the development of collagen-induced arthritis in mice

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 134(4)

Published: Dec. 19, 2023

Altered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking metabolites to disease are unknown. Using collagen-induced (CIA) model, we alterations metabolism, specifically indole, that correlated with disease. We demonstrated both bacteria dietary were required for indole supplementation was sufficient induce their absence. When mice CIA on a low-tryptophan diet supplemented observed significant increases serum IL-6, TNF, IL-1β; splenic RORγt+CD4+ T cells ex vivo collagen-stimulated IL-17 production; pattern of anti-collagen antibody isotype switching glycosylation corresponded increased complement fixation. IL-23 neutralization reduced severity indole-induced CIA. Finally, exposure human colonic lymphocytes expression genes involved signaling plasma cell activation. Altogether, propose mechanism by which intestinal dysbiosis during results altered catabolism, leading stimulation development. Blockade generation may present unique therapeutic pathway RA SpA.

Language: Английский

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Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 5, 2024

Abstract Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability disease impedes their study. Addressing this critical knowledge gap, we use experimental medicine approach immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes allowing detailed characterisation. Exploratory mass cytometry analyses reveal three circulating cellular subsets heralding onset – CD45RO + PD1 hi CD4 CD8 T cells, CD27 CD86 CD21 - B cells further single-cell sequencing. Distinct lymphocyte including cytotoxic exhausted memory CXCR5 IGHA1 plasma primed for activation patients. Regulatory (Treg cells) increase at onset, but with dysfunctional regulatory marker expression compared drug-free remission. Significant clonal expansion is observed not after cessation; widespread throughout cell limited granzyme-expressing subset within cells. Based on our observations, suggest a model immune dysregulation understanding RA flare, potential translational research towards novel avenues its treatment prevention.

Language: Английский

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Rheumatoid Arthritis: The Continuum of Disease and Strategies for Prediction, Early Intervention, and Prevention

The Journal of Rheumatology, Journal Year: 2024, Volume and Issue: 51(4), P. 337 - 349

Published: Jan. 15, 2024

Rheumatoid arthritis (RA) is known to include a pre-RA stage that can be defined as the presence of familial or genetic risk factors, biomarker abnormalities (eg, anticitrullinated protein antibodies [ACPA]), symptoms, and even abnormal imaging findings prior development onset clinical RA with inflammatory apparent on physical examination. Indeed, there are multiple completed ongoing retrospective case-control well prospective observational studies identify key biologic drivers disease. Further, building predictive ability combinations biomarkers, for future RA, trials completed, underway, in approaches may prevent, delay, ameliorate at-risk individuals. Importantly, however, although an effective preventive intervention has not yet been identified, individuals being increasingly identified care; this presents challenge how manage these practice. This review will discuss current understanding biology natural history development, nomenclature, models prediction evaluate prevention overall goal provide insights into challenges opportunities field prevention. Moreover, up-to-date options management at RA.

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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Microbial Mechanisms of Rheumatoid Arthritis Pathogenesis

Current Rheumatology Reports, Journal Year: 2024, Volume and Issue: 26(4), P. 124 - 132

Published: Feb. 1, 2024

Language: Английский

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The gut microbiome in systemic lupus erythematosus: lessons from rheumatic fever

Nature Reviews Rheumatology, Journal Year: 2024, Volume and Issue: 20(3), P. 143 - 157

Published: Feb. 6, 2024

Language: Английский

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