Long-term evolution of gut inflammation in patients with spondyloarthropathy
Abstract
BACKGROUND & AIMS: Intestinal inflammation has been observed in patients with spondyloarthropathy (SpA). This prospective study reports the evolution of the intestinal inflammation observed in patients with SpA. METHODS: One hundred twenty-three patients with SpA who had undergone initial endoscopy were clinically reassessed. Intestinal evolution was evaluated by ileocolonoscopy and the histological study of biopsy specimens in 49 patients. RESULTS: Articular remission rates were independent of initial gut inflammation and associated with endoscopic and histological remission. Persistent gut inflammation was observed in active joint disease. Gut inflammation rarely disappeared, despite the persistence of articular complaints. Initial chronic gut inflammation implied a high risk of evolution to ankylosing spondylitis. Evolution to inflammatory bowel disease (IBD) was observed in 7% of patients. Mainly patients with initial chronic inflammation and mild complaints of diarrhea were at risk. Sulfasalazine was more frequently needed in the treatment of patients with gut inflammation with a beneficial effect on articular and intestinal evolution but did not prevent evolution to IBD. CONCLUSIONS: This study supports the etiopathogenetic role of the gut in SpA. Presence of chronic gut inflammation and mild complaints of diarrhea implies a high risk of evolution to ankylosing spondylitis and IBD. Sulfasalazine has a beneficial effect on articular activity by controlling gut inflammation, but it cannot prevent evolution to overt IBD. (Gastroenterology 1996 Jun;110(6):1696-703)
References (0)
Cited by (200)
Serum biomarkers and their relationship to axial spondyloarthritis associated with inflammatory bowel diseases
2024, Autoimmunity ReviewsSpondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.
SpA plus IBD or IBD plus SpA: Does commutative property apply?
2023, Autoimmunity ReviewsThe term spondyloarthritis (SpA) encompasses a group of interrelated disorders characterised by the involvement of the musculoskeletal system as well as extra-articular manifestations like acute anterior uveitis, psoriasis and inflammatory bowel diseases (IBD). Likewise, IBD may present with various extra-intestinal manifestations among which those involving the musculoskeletal system, namely peripheral and axial SpA are the most common. The identification of patients with both SpA and IBD is of paramount importance in clinical practice since the coexistence of these two entities has been associated with great disability and decreased quality of life. In order to achieve an early diagnosis of IBD-SpA it is instrumental that rheumatologists seek for gastrointestinal symptoms in SpA patients and likewise that gastroenterologists seek for inflammatory musculoskeletal symptoms in patients with IBD. This narrative review aims at critically appraising the available evidence about SpA occurring in IBD patients versus IBD occurring in patients with SpA and at highlighting similarities and differences between the two scenarios.
Cytokines and intestinal epithelial permeability: A systematic review
2023, Autoimmunity ReviewsThe intestinal mucosa is composed of a well-organized epithelium, acting as a physical barrier to harmful luminal contents, while simultaneously ensuring absorption of physiological nutrients and solutes. Increased intestinal permeability has been described in various chronic diseases, leading to abnormal activation of subepithelial immune cells and overproduction of inflammatory mediators. This review aimed to summarize and evaluate the effects of cytokines on intestinal permeability.
A systematic review of the literature was performed in the Medline, Cochrane and Embase databases, up to 01/04/2022, to identify published studies assessing the direct effect of cytokines on intestinal permeability. We collected data on the study design, the method of assessment of intestinal permeability, the type of intervention and the subsequent effect on gut permeability.
A total of 120 publications were included, describing a total of 89 in vitro and 44 in vivo studies. TNFα, IFNγ or IL-1β were the most frequently studied cytokines, inducing an increase in intestinal permeability through a myosin light-chain-mediated mechanism. In situations associated with intestinal barrier disruption, such as inflammatory bowel diseases, in vivo studies showed that anti-TNFα treatment decreased intestinal permeability while achieving clinical recovery. In contrast to TNFα, IL-10 decreased permeability in conditions associated with intestinal hyperpermeability. For some cytokines (e.g. IL-17, IL-23), results are conflicting, with both an increase and a decrease in gut permeability reported, depending on the study model, methodology, or the studied conditions (e.g. burn injury, colitis, ischemia, sepsis).
This systematic review provides evidence that intestinal permeability can be directly influenced by cytokines in numerous conditions. The immune environment probably plays an important role, given the variability of their effect, according to different conditions. A better understanding of these mechanisms could open new therapeutic perspectives for disorders associated with gut barrier dysfunction.
Interactions between NSAIDs, opioids and the gut microbiota - Future perspectives in the management of inflammation and pain
2023, Pharmacology and TherapeuticsThe composition of intestinal microbiota is influenced by a number of factors, including medications, which may have a substantial impact on host physiology. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are among those widely used medications that have been shown to alter microbiota composition in both animals and humans. Although much effort has been devoted to identify microbiota signatures associated with these medications, much less is known about the underlying mechanisms. Mucosal inflammation, changes in intestinal motility, luminal pH and bile acid metabolism, or direct drug-induced inhibitory effect on bacterial growth are all potential contributors to NSAID- and opioid-induced dysbiosis, however, only a few studies have addressed directly these issues. In addition, there is a notable overlap between the microbiota signatures of these drugs and certain diseases in which they are used, such as spondyloarthritis (SpA), rheumatoid arthritis (RA) and neuropathic pain associated with type 2 diabetes (T2D). The aims of the present review are threefold. First, we aim to provide a comprehensive up-to-date summary on the bacterial alterations caused by NSAIDs and opioids. Second, we critically review the available data on the possible underlying mechanisms of dysbiosis. Third, we review the current knowledge on gut dysbiosis associated with SpA, RA and neuropathic pain in T2D, and highlight the similarities between them and those caused by NSAIDs and opioids. We posit that drug-induced dysbiosis may contribute to the persistence of these diseases, and may potentially limit the therapeutic effect of these medications by long-term use. In this context, we will review the available literature data on the effect of probiotic supplementation and fecal microbiota transplantation on the therapeutic efficacy of NSAIDs and opioids in these diseases.
Novel therapies in axial spondyloarthritis
2022, Best Practice and Research: Clinical RheumatologyOver the past two decades, advancements in understanding the pathogenesis of axial spondyloarthritis have led to discoveries of new therapeutic targets, particularly the interleukin-17, tumor necrosis factor axis, and Janus kinase-signal transducer and activator of transcription pathway. While many of the available agents have proven to be efficacious and safe for the treatment of axial spondyloarthritis, a remarkable percentage of patients either fail or cannot tolerate these medications. This has prompted researchers to look for new targets that would maximize efficacy and minimize toxicity. In this article, we review novel agents that were recently approved, in trials, and possible future targets or mechanisms. We also discuss their role as it pertains to the prevention of radiographic progression and the management of extra-musculoskeletal manifestations.
The association between intestinal microbiome and autoimmune uveitis
2022, Archivos de la Sociedad Espanola de OftalmologiaEl microbioma está fuertemente implicado en un amplio espectro de enfermedades inmunomediadas, mientras que la microbiota comensal intestinal juega un papel fundamental en la homeostasis inmunológica e intestinal.
Se realizó una búsqueda exhaustiva de la literatura en la base de datos PubMed. Se realizó una búsqueda adicional en Google Scholar para completar los elementos recopilados.
Debido a las complejas interacciones con la genética del huésped y otros factores, la disbiosis intestinal se ha relacionado con varios trastornos inmunomediados. En particular, el papel de la microbiota intestinal en la patogenia de la uveítis ha sido demostrado por varios estudios, lo que indica que los cambios en el microbioma pueden desencadenar procesos inflamatorios oculares autoinmunes o afectar su gravedad.
Esta revisión resume cómo las alteraciones en la microbiota intestinal pueden conducir a patologías oculares inmunomediadas y cómo el microbioma puede ser dirigido para formar nuevos enfoques terapéuticos para tratar estas condiciones severas y potencialmente cegadoras.
The microbiome is strongly implicated in a wide spectrum of immune-mediated diseases, whereas gut commensal microbiota plays a pivotal role in immune and intestinal homeostasis.
A thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items.
Due to complex interactions with the host genetics and other factors, intestinal dysbiosis has been linked to various immune-mediated disorders. In particular, the role of intestinal microbiota in the pathogenesis of uveitis has been demonstrated by several studies, indicating that changes in the microbiome can trigger autoimmune ocular inflammatory processes or affect their severity.
This review summarizes how alterations in the intestinal microbiota can conduce to immune-mediated ocular pathologies and how microbiome can be targeted in order to form novel therapeutic approaches to treat these severe and potentially blinding conditions.