Mucosal immunity and rheumatoid arthritis: An update on mechanisms and therapeutic potential

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: 24(5), P. 103775 - 103775

Published: Feb. 13, 2025

Rheumatoid Arthritis (RA) is a persistent autoimmune inflammatory disorder that arises from the intricate interaction between genetic predisposition and environmental influences. The progression of RA can be delineated into four distinct phases: initially, influence risk factors; followed by emergence systemic autoimmunity; subsequently, an asymptomatic phase; ultimately, manifestation clinical arthritis. Recently, role mucosal immunity in has gained significant attention research. Evidence published studies suggests not only influences onset but also plays crucial its progression. Scholars have begun to unravel links barriers gastrointestinal tract, respiratory system, oral cavity. Specifically, shifts microbiota, dysfunction barriers, abnormal activation immune tissues are all implicated pathogenesis RA.Despite this growing body knowledge, comprehensive review therapeutic implications yet conducted. This emphasizes driving abnormalities development autoimmunity rheumatoid arthritis (RA). It further explores potential RA, as well issues challenges need addressed current research field, providing new perspective targets for prevention treatment RA.

Language: Английский

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Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut

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

Published: Sept. 26, 2023

Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA produce variable haplotypes that specifically correlated pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share same risk-associated often resulting in comorbidity. This shared risk remains an unanswered question field. Yet, several groups have revealed links between gut microbial community composition and diseases. Autoimmunity is frequently dysbiosis, loss barrier function permeability tight junctions, which increases class II expression levels thus further influences microbiome. However, autoimmune-risk-associated connected to dysbiosis long before autoimmunity even begins. review evaluates current research on HLA-microbiome-autoimmunity triplex proposes pre-autoimmune bacterial important determinant comorbidities systemic inflammation as a common denominator.

Language: Английский

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Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(13), P. 4359 - 4359

Published: June 28, 2023

Rheumatoid arthritis (RA) synovitis is dominated by monocytes/macrophages with inflammatory patterns resembling microbial stimulation. In search of triggers, we reduced the intestinal microbiome in 20 RA patients (open label study DRKS00014097) bowel cleansing and 7-day fasting (≤250 kcal/day) performed immune monitoring sequencing. Patients metabolic syndrome (n = 10) served as a non-inflammatory control group. Scores disease activity (DAS28/SDAI) declined within few days were improved 19 after breaking fast (median ∆DAS28 -1.23; ∆SDAI -43%) or even achieved remission (DAS28 < 2.6/n 6; SDAI 3.3/n 3). Cytometric profiling 46 different surface markers revealed most pronounced phenomenon to be an initially increased monocyte turnover, which microbiota reduction fasting. Serum levels IL-6 zonulin, indicator mucosal barrier disruption, decreased significantly. Endogenous cortisol during but insufficient explain marked improvement. Sequencing indicated that potentially arthritogenic bacteria changed composition species broader capabilities. More eukaryotic, predominantly fungal colonizers observed RA, suggesting possible involvement. This demonstrates direct link between RA-specific inflammation could etiologically relevant would support targeted nutritional interventions against gut dysbiosis causal therapeutic approach.

Language: Английский

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Impact of Preoperative Biliary Stenting on Intestinal Dysfunction and Perioperative Complications After Pylorus-Preserving Pancreaticoduodenectomy

Medicina, Journal Year: 2025, Volume and Issue: 61(3), P. 391 - 391

Published: Feb. 24, 2025

Background and Objectives: Preoperative biliary stenting (PBS) is commonly used to manage obstructive jaundice in patients undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). However, the impact of PBS on intestinal barrier function perioperative complications remains controversial. This study aims evaluate effect dysfunction surgical outcomes, focusing influence stent duration. Materials Methods: In this prospective cohort study, 235 PPPD for resectable pancreatic neoplasms at Timișoara Municipal Emergency Clinical Hospital (2016–2024) were analyzed. Patients divided into two groups: those with (n = 98) without 137). Intestinal was assessed pre- postoperatively using biomarkers such as zonulin, fecal calprotectin, serum lipopolysaccharides (LPS). Perioperative including fistula, delayed gastric emptying (DGE), infections, hospital stay, compared. Additionally, outcomes stratified based duration (2–3 weeks vs. 3–4 weeks). Results: associated significantly higher levels LPS postoperatively, indicating compromised function. The stented group had a incidence fistulas (Grade B/C: 27.5% 13.1%, p < 0.01), DGE (25.5% 0.008), postoperative infections (34.7% 17.5%, 0.002), prolonged stay (16.9 ± 4.2 days 14.5 3.7 days, 0.019). Prolonged (3–4 weeks) worse compared shorter durations weeks), increased rates sepsis, ICU (p 0.05 all comparisons). Conclusions: dysfunction, systemic inflammation, following PPPD. (>3 further exacerbate these risks. Limiting 2–3 weeks, alongside optimized management, may help reduce morbidity improve outcomes.

Language: Английский

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Dual regulatory effects of gut microbiota and their metabolites in rheumatoid arthritis: balancing pathogenic and protective mechanisms

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Rheumatoid arthritis is a chronic autoimmune disorder characterized by destructive, symmetric joint inflammation and synovitis, resulting in substantial disability that profoundly compromises patients' quality of life. Its pathogenesis encompasses complex interactions between genetic environmental factors. Recent advances bacterial DNA sequencing technologies have uncovered significant correlation the human gut microbiota composition rheumatoid progression. Growing clinical experimental evidence establishes gut-joint axis as crucial mediator pathogenesis. Comprehensive investigation microbial communities their metabolites' influence on mechanisms, coupled with elucidation microbiome's bidirectional regulatory effects disease development, not only deepens our understanding pathological processes but also theoretical framework for developing novel diagnostic biomarkers personalized therapeutic interventions to enhance patient outcomes.

Language: Английский

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Profiling of fecal analytes as a potential biomarker in rheumatoid arthritis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 19, 2025

Background Loss of gut barrier integrity has been observed in rheumatoid arthritis (RA). While systemic inflammation RA extensively investigated, intestinal-specific inflammatory processes remain poorly understood. This study is designed to identify a novel biomarker panel combining fecal cytokine profiles with biomarkers discriminate patients varying disease progression. Methods Feces (Fc) and plasma (Pl) were obtained from 62 Naive (NA), 47 remission (RE), 28 difficult-to-treat patients(D2T), 70 healthy controls (HC). A 12 cytokines markers, including intestinal Fatty-Acid-Binding Protein-2 (FABP2), zonulin, Hypoxia-Inducible Factor-2α (HIF-2α), D-lactate, LBP calprotectin (FCAL), was quantified by ELISA. Statistical integration clinical parameters performed using univariate multivariate approaches. Results NA D2T demonstrated marked elevations pro-inflammatory compared RE HC groups, IL-6, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), IL-1 beta (IL-1β), Interferon-gamma (INF-γ), IL-23, Tumor Necrosis Factor-Alpha (TNF-α), IL-21, IL-17A/F, IL-22. Fecal zonulin HIF-2α significantly elevated both whereas D-lactate showed pronounced decrease the groups. These strongest correlation severity indices. Receiver operating characteristic (ROC) analysis revealed that FABP2, exhibited superior discriminative capacity between remarkable diagnostic potential for distinguishing groups counterparts. The discriminant scores (DS) model incorporating discriminatory performance utilizing top five parameters. Conclusions Our profiling methodology provides insights into mucosal microenvironment during dissociation underscores critical importance localized immune monitoring management.

Language: Английский

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Ernährung bei rheumatischen Erkrankungen – Bedeutung für Erkrankungsrisiko und Aktivität

Arthritis und Rheuma, Journal Year: 2025, Volume and Issue: 45(02), P. 117 - 121

Published: April 1, 2025

Zusammenfassung Individuelle Ernährungsgewohnheiten können auf die entzündliche Aktivität rheumatischer Erkrankungen Einfluss nehmen. Eine hyperkalorische Ernährung mit einem hohen Anteil prozessierter, zucker- und fettreicher sowie ballaststoffarmer Nahrungsmittel kann nicht nur zu einer metabolischen Fehlregulation führen, sondern auch inflammatorische Prozesse fördern. Obgleich Evidenz schwach ist, scheint insbesondere eine hohe Adhärenz zur mediterranen einen günstigen Effekt haben. individuelle Ernährungsberatung ist ein modernes Beispiel für personalisierte Medizin ermutigt Betroffene, das „Selbst-Management“ stärken. So Ernährungsinterventionen als Ergänzung (nicht jedoch Ersatz) der medikamentösen Basistherapie betrachtet werden.

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Exploring the pathogenesis of RA through the gut‐articular axis‐dysbiosis a potential factor

Clinical Anatomy, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 27, 2024

Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex etiology. It has been suggested that the pathogenesis of RA begins in mucosa and then transitions to joints when many factors interact, including microbial dysbiosis, inflammatory responses, immune abnormalities at mucosal site. Data from animals patients suggest there are changes microflora before onset RA, dysbiosis ecology continues play role development arthritis. Microbial reduces normal barrier function intestinal tract, promotes reactions areas intestines, activates cells abnormally produce large number auto-reactive antibodies exacerbate Current findings do not clarify whether only potential trigger for RA. If it possible intervene such could clinical symptoms be prevented or reduced? Finding new ways regulate gut flora composition maintain an ongoing challenge prevention treatment

Language: Английский

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Gut Dysbiosis and Dietary Interventions in Rheumatoid Arthritis—A Narrative Review

Nutrients, Journal Year: 2024, Volume and Issue: 16(18), P. 3215 - 3215

Published: Sept. 23, 2024

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease. The pathogenesis of RA complex involves interactions between articular cells, such as fibroblast-like synoviocytes, immune cells. These cells secrete pro-inflammatory cytokines, chemokines, metalloproteinases other molecules that together participate in joint degradation. current evidence suggests the important immunoregulatory role gut microbiome, which can affect susceptibility to diseases infections. An altered phenomenon known dysbiosis, associated with development inflammatory diseases. Importantly, profile microbiome depends on dietary habits. Therefore, elements interventions indirectly impact progression This review summarises involvement dysbiosis diet RA.

Language: Английский

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Mechanism of action of Nrf2 and its related natural regulators in rheumatoid arthritis

Journal of Orthopaedic Surgery and Research, Journal Year: 2024, Volume and Issue: 19(1)

Published: Nov. 14, 2024

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis that can lead to joint deformities. To date, more than 18 million individuals worldwide have been diagnosed with RA, making it one of the most prevalent diseases globally and posing a significant threat public health safety. Due complex pathogenesis disease, which involves autoimmunity, genetics, inflammation oxidative stress in body's tissues, current drug therapy generally targets single molecule, effective efficient drugs involving multiple levels are lacking; thus, there urgent need for high-quality research treatment this field. Nuclear transcription factor erythroid 2-associated 2 (Nrf2) plays crucial role cellular resistance electrophilic attacks potential pharmacological target chronic treatment. While currently no Nrf2 approved specifically RA treatment, such approach holds great significance. In recent years, use natural products treat other conditions has become increasingly widespread because their superior efficacy minimal side effects. Therefore, article provides review mechanism summarizes its associated pathways aiming offer new insights strategies prevention management RA.

Language: Английский

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