Spondyloarthritis (SpA) is the most common extraintestinal manifestation of inflammatory bowel disease (IBD). The application of screening tools to detect SpA in patients with IBD may lead to earlier recognition of SpA and affect treatment decisions.

A combination of two previously described SpA screening questionnaires, the Detection of Arthritis in Inflammatory Bowel Disease (DETAIL) and IBD Identification of Spondyloarthritis Questionnaire (IBIS-Q), was administered to consecutive patients with IBD attending IBD specialty clinics in six US academic medical centers. Demographic data, IBD, and rheumatology history were extracted by chart review.

A total of 669 patients were analyzed. The median age was 40 years (interquartile range [IQR] 30-54) with a median disease duration of 12 years (IQR 6-22) and moderate to severe IBD based on medication exposure and history of bowel surgery. A total of 81 patients (12%) carried a diagnosis of an inflammatory rheumatic disease, whereas 75 (11%) had consulted a rheumatologist during the previous year. Using published cutoffs, 180 out of 669 patients (27%) screened positive with DETAIL, 266 (40%) with IBIS-Q, and 275 (41%) with either questionnaire. Axial symptoms were more frequently reported than peripheral musculoskeletal complaints. Notably, 189 out of 275 (69%) screen-positive patients had neither a documented inflammatory rheumatic disease diagnosis nor a visit with a rheumatologist within the past year.

A substantial proportion of patients with IBD have symptoms suggestive of SpA, and many of these may have undiagnosed SpA. The IBIS-Q questionnaire appears to identify more potential SpA cases than DETAIL. Strategies are needed to prioritize rheumatology consultations for those patients with IBD who are most likely to benefit.

Fucoxanthin, an abundant carotenoid in marine algae, has garnered attention for its diverse health benefits, including anti-inflammatory and anticancer properties. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage. This study investigated the therapeutic potential of fucoxanthin extracted from Phaeodactylum tricornutum in collagen-induced RA. Our results demonstrated that fucoxanthin significantly alleviated RA symptoms, including weight loss, joint swelling, and decreased appetite. Histological analysis revealed that fucoxanthin mitigated synovial inflammation, cartilage damage, and bone erosion. Mechanistically, transcriptomic analysis and cell experiments indicated that fucoxanthin suppressed the JAK-STAT signaling pathway by downregulating the expression of inflammatory cytokines, such as IL-6 and IL-1β. Furthermore, metagenomic analysis suggested that fucoxanthin restored the altered gut microbiota composition associated with RA. These findings highlight the therapeutic potential of fucoxanthin from P. tricornutum in the management of RA by targeting multiple pathways, including inflammation and gut microbiota.

Study DesignRetrospective cohort study.ObjectivesPatients with IBD are at an increased risk for postoperative complications following surgery. The goal of this study is to investigate if inflammatory bowel disease (IBD) is a risk factor for complications following lumbar discectomy.MethodsWe identified IBD patients who underwent lumbar discectomy for lumbar disc herniation (LDH) and matched to them with controls without IBD in a1:5 ratio. We excluded patients with a history of spinal injury, cancer, infection, trauma, or surgery to remove the digestive tract. We used multivariate logistic regression analyses to compare postoperative outcomes, including 90-day complications, 90-day emergency department visits, and 90-day readmissions. In addition, 2-year re-discectomy rates and a 3-year lumbar fusion rate were compared between the cohorts.ResultsAfter applying the study criteria, we identified 6134 IBD patients with LDH for further analysis. With the exception of dura tears, patients with IBD had significantly higher rates of medical complications, incision-related complications, ED visits, and readmission rates compared to patients without IBD, especially for the 2-year and 3-year rates of disc recurrence and revision surgery.ConclusionsPatients with IBD who underwent lumbar discectomy are at a significantly higher rate of complications. Therefore, spine surgeons and other health care providers should be aware of this higher risk associated with IBD patients and properly treat the patients' IBD before surgery to lower these risks.

Musculoskeletal involvement in inflammatory bowel disease (IBD) patients contributes to poorer outcomes and reduced quality of life (QoL). We aimed to describe the prevalence and distribution of peripheral and axial musculoskeletal symptoms and clinical findings in patients with IBD prior to biological treatment.

Bio-naïve patients with IBD were consecutively recruited. Musculoskeletal symptoms were assessed using questionnaires and a structured interview. A rheumatologist conducted a clinical evaluation of peripheral joints and entheses, spine mobility, and considered various differential diagnoses.

Of 82 patients (ulcerative colitis (UC): 33, Crohn's disease (CD): 49, mean age 46 years, 55% male), 51 (62.2%) had musculoskeletal symptoms and 51 (62.2%) had clinical findings. Peripheral joint pain was reported by 39 (47.6%) patients, entheseal pain by 15 (18.3%), and back pain by 33 (40.2%) patients. Clinical evaluation revealed arthritis in 24 (29%) patients and enthesitis in 50 (61%); enthesitis was asymptomatic in 72% of the cases. The Assessment of Spondyloarthritis international Society (ASAS) classification criteria for peripheral spondyloarthritis were met in 36 (44%) patients, and for fibromyalgia in 7 (8.5%) patients. Being female was associated with more frequent musculoskeletal symptoms and clinical findings. Significantly more patients with CD reported joint pain, but no differences in clinical findings were observed between UC and CD, nor between those with active and inactive IBD.

Two-thirds of patients with IBD scheduled for their first biological treatment exhibited musculoskeletal involvement, sometimes asymptomatically. Axial and peripheral symptoms were equally common. A multidisciplinary approach is crucial for early detection and integrated treatment aiming for remission in all disease domains to improve patients' QoL.

Tristetraprolin (TTP, encoded by Zfp36) is an RNA-binding protein that plays a major role in the control of inflammation. Zfp36-/- mice spontaneously develop a complex multiorgan inflammatory syndrome but no overt intestinal inflammation, suggesting the involvement of local regulatory mechanisms. In this study, we observed local expansion of IL-22-producing type 3 innate lymphoid cells (ILC3s) in the lamina propria of Zfp36-/- mice. Our findings demonstrate that this expansion was primarily influenced by cell-extrinsic cues. In the absence of IL-22, we observed delayed onset of arthritis in Zfp36-/- mice but no clear evidence of exacerbated intestinal inflammation under steady-state conditions. However, we show that Zfp36-/- mice were paradoxically protected from dextran sulfate sodium (DSS)-induced colitis and suggest that increased IL-22 production by ILC3 might contribute to this observation. Taken together, these data highlight the complex interplay between systemic inflammation and gut mucosal immune homeostasis.

Spondyloarthritis (SpA) exhibits predominantly musculoskeletal symptoms but also significant gastrointestinal (GI) and psychological manifestations. Subclinical gut inflammation is common in SpA, with frequent symptoms such as abdominal pain and diarrhea. Psychological issues like depression and anxiety are also prevalent, with a negative impact on quality of life. This study aimed to evaluate the presence of GI and psychiatric symptoms in SpA patients without inflammatory bowel disease (IBD) and their association with disease characteristics.

Cross-sectional study, which included SpA patients from two rheumatology outpatient clinics. Patients were assessed for GI, and depressive symptoms (PHQ-9), perceived stress (PSS-10), disease activity (ASDAS, BASDAI) and functionality (BASFI). Laboratory tests included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and Secretory IgA. Statistical analysis involved Spearman correlation, linear regression, and multiple correspondence discriminant analysis (MCDA).

Among 98 SpA patients, 79.6% had axial SpA. High disease activity and functional impairment were common. 65.3% reported ≥ 2 GI symptoms, predominantly abdominal pain and diarrhea. Depression (PHQ-9 ≥ 10) was observed in 46.7% of patients, being moderate to severe in 25.0%. Depression, perceived helplessness, and lack of self-efficacy were associated with high disease activity and GI symptoms. MCDA identified strong correlations between depression, GI symptoms, and disease activity.

This study highlights the association between GI and psychological symptoms with disease activity and functionality in SpA patients. Depression and perceived helplessness are prevalent and closely associated with high disease activity and GI symptoms, suggesting the need for interdisciplinary management from early stages to improve patient outcomes.

Arthritis is associated with varying degrees of intestinal inflammation and microbiota dysbiosis, leading to the 'gut-joint axis hypothesis' in which intestinal and joint inflammation are suggested to be interconnected through immune-microbiota interactions. While clinical observations support this, causality remains uncertain. Rodent models have provided insights into potential mechanisms by uncovering microbial influences and immune pathways that either connect or uncouple gut and joint inflammation. Based on recent findings, we propose the 'immune hypersensitivity hypothesis' whereby central immune hyper-reactivity can independently drive joint inflammation via local sterile triggers, and gut inflammation via microbial triggers. We argue that this suggests a more nuanced role of the microbiota in arthritis pathogenesis that varies according to the predominant immune mechanisms in disease subtypes. We explore gut-immune interactions in arthritis, highlight ongoing challenges, and propose future research directions.

Reactive arthritis (ReA) provides a unique opportunity to comprehend how a mucosal infection leads to inflammatory arthritis at a distant site without the apparent invasion of the pathogen. Unfortunately, conventional stool cultures after ReA provide limited information, and there is a dearth of metagenomic studies in ReA. The objective of this study was to identify gut microbiota associated with the development of ReA.

Patients with ReA or undifferentiated peripheral spondyloarthritis (UpSpA) were included if they presented within 4 weeks of the onset of the current episode of arthritis. Metagenomic DNA was extracted from the stools of these patients and of 36 age- and sex-similar controls. Sequencing and analysis were done using a standard 16S ribosomal pipeline.

Of 55 patients, there was no difference between the gut microbiota of postdiarrheal ReA (n = 20) and of upSpA (n = 35). Comparing the gut microbiota of patients vs healthy controls, the patients had significantly higher alpha and beta diversity measures. After stringency filters, Proteobacteria had high abundance while Firmicutes had lesser as compared with the controls. Six families were overexpressed in patients, while another five were overexpressed in controls. Sixteen genera and 18 species were significantly different between patients and controls. At the species level there was strong association of Staphylococcus aureus, Clostridium septicum Klebsiella pneumoniae, Escherichia coli, Empedobacter brevis, Roseburia hominis, Bacillus velezensis and Crassaminicella with ReA.

The microbiota of classical gut-associated ReA and upSpA is similar. Patients have higher diversities in their gut microbiota compared with healthy controls. Both known and previously unreported species associated with ReA/upSpA were identified.

The strong association of the human leukocyte antigen B∗27 alleles (HLA-B∗27) with spondyloarthritis and related rheumatic conditions has long fascinated researchers, yet the precise mechanisms underlying its pathogenicity remain elusive. Here, we review how interplay between the microbiome, the immune system, and the enigmatic HLA-B∗27 could trigger spondyloarthritis, with a focus on whether HLA-B∗27 presents an arthritogenic peptide. We propose mechanisms by which the unique biochemical characteristics of the HLA-B∗27 protein structure, particularly its peptide binding groove, could dictate its propensity to induce pathological T cell responses. We further provide new insights into how TRBV9+ CD8+ T cells are implicated in the disease process, as well as how the immunometabolism of T cells modulates tissue-specific inflammatory responses in spondyloarthritis. Finally, we present testable models and suggest approaches to this problem in future studies given recent advances in computational biology, chemical biology, structural biology, and small-molecule therapeutics.

Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased functional genomics approach. We integrated genome-wide association study (GWAS) data with epigenomic and transcriptomic datasets of human immune cells. To quantify enrichment of cell type-specific open chromatin or gene expression in AS risk loci, we used three published methods-LDSC-SEG, SNPsea, and scDRS-that have successfully identified relevant cell types in other diseases. Natural killer (NK) cell-specific open chromatin regions are significantly enriched in heritability for AS, compared to other immune cell types such as T cells, B cells, and monocytes. This finding was consistent between two AS GWAS. Using RNA sequencing data, we validated that genes in AS risk loci are enriched in NK cell-specific gene expression. Using the human Space-Time Gut Cell Atlas, we also found significant upregulation of AS-associated genes predominantly in NK cells. We performed co-localization analyses between GWAS risk loci and genetic variants associated with gene expression (eQTL) to find putative target genes. This revealed four AS risk loci affecting regulation of candidate target genes in NK cells: two known loci, ERAP1 and TNFRSF1A, and two understudied loci, ENTR1 (SDCCAG3) and B3GNT2. Our findings suggest that NK cells may play a crucial role in AS development and highlight four putative target genes for functional follow-up in NK cells.

Osteoarthritis (OA) is a common progressive degenerative disease. Gut microbiota (GM) and their metabolites have been closely associated with the onset, progression, and pathology of OA. GM and their metabolites may influence the cartilage directly, or indirectly by affecting the gut, the immune system, and the endocrine system. They function through classical pathways in cartilage metabolism and novel pathways that have recently been discovered. Some of them have been used as targets for the prevention and treatment of OA. The current study sought to describe the major pathological signaling pathways in OA chondrocytes and the potential role of gut-related factors in these pathways.

In patients with inflammatory bowel disease (IBD), co-occurring spondyloarthritis (SpA) leads to poorer outcomes and impaired quality of life, highlighting the importance of early detection and effective treatment. This is the first study to assess the prevalence and distribution of axial symptoms and magnetic resonance imaging (MRI)-detected involvement of the spine and sacroiliac joints (SIJs) in early IBD.

Newly diagnosed patients with IBD from a prospective, population-based cohort were consecutively recruited. Rheumatological interview, clinical, ultrasound, and MRI assessment for SIJ and spine inflammatory and structural lesions were made using validated scoring methods and consensus definitions of axial SpA (axSpA).

Of 110 patients (ulcerative colitis: 70, Crohn's disease: 40, mean age of 42 years, and 40% male), 48 (44.9%) reported back and/or buttock pain, and 10 (9.1%) had inflammatory back pain. Seventeen (16.7%) patients had MRI findings indicative of axSpA; only 10 of these patients had axial symptoms. Inflammatory MRI lesions were present in SIJs and the spine of 27 (26.5%) and 30 (30.3%) patients, respectively. The Assessment of SpondyloArthritis International Society classification criteria for axSpA were met in 11 (10%) cases. MRI findings typical of axSpA were associated with peripheral joint and entheseal inflammation detected by ultrasound ( P = 0.04). No differences in clinical or imaging findings were found between patients with ulcerative colitis and Crohn's disease.

One-in-6 newly diagnosed patients with IBD had MRI findings indicative of axSpA. As 40% of these patients were asymptomatic, this suggests that axSpA is underdiagnosed in early IBD. Multidisciplinary collaboration is essential to ensure early detection of axial inflammation and to enable optimal therapy preventing future structural damage and disability.

The objective of this study is to investigate lipopolysaccharid-binding protein (LBP), zonulin and calprotectin as markers of bacterial translocation, disturbed gut barrier and intestinal inflammation in patients with radiographic axial spondyloarthritis (r-axSpA) during tumour necrosis factor inhibitor (TNFi) therapy and to analyze the association between disease activity, response to treatment and biomarker levels.

Patients with active r-axSpA of the German Spondyloarthritis Inception Cohort starting TNFi were compared with controls with chronic back pain. Serum levels of LBP, zonulin and calprotectin were measured at baseline and after 1 year of TNFi therapy. We analysed the longitudinal association between biomarkers and disease activity, and the relationship between biomarkers and treatment response with regression analysis.

121 patients with r-axSpA were compared with 63 controls. At baseline, patients with r-axSpA had higher levels of LBP and calprotectin than controls, which decreased significantly during TNFi treatment. LBP showed a positive association in longitudinal analyses with Axial Spondyloarthritis Disease Activity Score (ASDAS) (ß=0.08, 95% CI 0.06 to 0.10), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (ß=0.08, 95% CI 0.04 to 0.12) and C reactive protein (CRP) (ß=1.69, 95% CI 1.04 to 2.34). Calprotectin was associated with ASDAS (ß=0.04, 95% CI 0.01 to 0.07) and CRP (ß=0.82, 95% CI 0.27 to 1.37). Furthermore, LBP and calprotectin levels at baseline showed an association with a subsequent change in BASDAI. Baseline zonulin levels were not significantly associated with disease activity or treatment response.

Serum levels of LBP and calprotectin are associated with disease activity in patients with r-axSpA and decrease with TNFi response. In contrast, serum zonulin levels showed no association with disease activity or treatment response, arguing against a strict correlation between intestinal permeability and disease activity in axSpA.

Ankylosing spondylitis (AS) patients often present with microscopic signs of gut inflammation. We used proteomic techniques to identify the differentially expressed proteins (DEPs) in the colon tissues of patients with AS and patients with gut inflammation, and then used investigated the influence of NMRAL1 protein on inflammatory cytokines to explore its potential role in the pathogenesis of AS and gut inflammation.

Colonic mucosal tissues were collected from four different groups: healthy individuals (group A), patients with gut inflammation only (group B), patients with AS only (group C), and patients with AS combined with gut inflammation (group D). A total of 20 samples were processed for proteomic analysis, wherein proteins were extracted using SDT lysis, followed by separation via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The proteins were digested using the filter-aided sample preparation (FASP) method and then analyzed using a timsTOF Pro mass spectrometer. The resulting peptide data were used to identify differentially expressed proteins (DEPs) across the different groups. To further explore the inflammation-related function of NMRAL1 protein, the murine monocyte/macrophage cell line RAW264.7 was used. NMRAL1 mRNA expression levels were assessed via RT-qPCR, and inflammatory cytokine levels (TNF-α, IL-1β, IL-17 and IL-23) were measured using ELISA following NMRAL1 siRNA transfection in LPS-treated macrophages.

We collected colonic mucosa specimens from 20 patients, including groups A,B, C and D with 5 patients in each group. We established a database of DEPs and identified 107 (63 upregulated and 44 downregulated) between group B and group A, 78 (16 upregulated and 62 downregulated) between group D and group C, 45 (8 upregulated and 37 downregulated) between group D and group B, and 57 (33 upregulated and 24 downregulated) between group C and group A. Further analysis revealed that the NmrA-like family domain containing 1 (NMRAL1) protein was identified as a DEP specifically associated with group D. The results of in vitro results showed a significant decrease in NMRAL1 mRNA expression in LPS-treated cells (P<0.001), which was further reduced in NMRAL1 siRNA-transfected cells (P<0.0001), confirming successful transfection. ELISA results revealed that the levels of key inflammatory cytokines (TNF-α, IL-1β, IL-17 and IL-23) were significantly elevated in the LPS-treated model group (P<0.0001, P<0.001), but these levels were significantly decreased after NMRAL1 siRNA transfection (P<0.0001, P<0.01, P<0.05).

NMRAL1 is identified as a key differentially expressed protein in AS patients with gut inflammation. Knockdown of NMRAL1 significantly reduced the levels of inflammatory cytokines, suggesting its potential role in the pathogenesis of AS and gut inflammation, and as a possible therapeutic target.

Liver metabolites are involved in the progression of rheumatoid arthritis (RA), indicating a connection between the liver and joints. However, the impact and mechanism of Hepatitis B virus (HBV), a hepatotropic virus, on RA are still unclear. We investigated the correlation between HBV and RA using Mendelian randomization analysis. Single-cell transcriptome analysis was conducted to investigate changes in cell subtypes in synovial tissue of HBV-RA patients. Fibroblast-like synoviocytes (FLS) were used to create a cell model, and the transcriptome was examined to identify the key downstream molecules of FMT regulated by HBx. CIA model was constructed using HBV transgenic, HBx transgenic, and TRADF1 knockout mice to investigate the impact and mechanism of HBV on CIA. The results of our study revealed a significant positive correlation between HBV and RA. The functional studies identified a crucial role of fibroblast-myofibroblast transition (FMT) in the progression of RA. The results suggest that HBV-encoded HBx may promote FMT in RA by upregulating TRAFD1. Furthermore, trans-ferulic acid (TFA) was identified by screening for common metabolites in the liver, joints, and peripheral blood using the metabolome and WGCNA. Interestingly, we found that TFA ameliorated HBx-induced RA by suppressing TRAFD1 expression. Our study demonstrates that hidden liver-joint axis, an imbalance between TFA and HBx, plays a critical role in HBV-induced RA, which could be a potential strategy for preventing RA development.

With the imbalance of intestinal microbiota, the body will then face an inflammatory response, which has serious implications for human health. Bodily allergies, injury or pathogens infections can trigger or promote inflammation and alter the intestinal environment. Meanwhile, excessive changes in the intestinal environment cause the imbalance of microbial homeostasis, which leads to the proliferation and colonization of opportunistic pathogens, invasion of the body's immune system, and the intensification of inflammation. Some natural compounds and gut microbiota and metabolites can reduce inflammation; however, the details of how they interact with the gut immune system and reduce the gut inflammatory response still need to be fully understood. The review focuses on inflammation and intestinal microbiota imbalance caused by pathogens. The body reacts differently to different types of pathogenic bacteria, and the ingestion of pathogens leads to inflamed gastrointestinal tract disorders or intestinal inflammation. In this paper, unraveling the interactions between the inflammation, pathogenic bacteria, and intestinal microbiota based on inflammation caused by several common pathogens. Finally, we summarize the effects of intestinal metabolites and natural anti-inflammatory substances on inflammation to provide help for related research of intestinal inflammation caused by pathogenic bacteria.

The IL-23 signaling pathway in both innate and adaptive immune cells is vital for orchestrating type 17 immunity, which is marked by the secretion of signature cytokines such as IL-17, IL-22, and GM-CSF. These proinflammatory mediators play indispensable roles in maintaining intestinal immune equilibrium and mucosal host defense; however, their involvement has also been implicated in the pathogenesis of chronic inflammatory disorders, such as inflammatory bowel diseases and autoimmunity. However, the implications of type 17 immunity across diverse inflammation models are complex. This review provides a comprehensive overview of the multifaceted roles of these cytokines in maintaining gut homeostasis and in perturbing gut barrier integrity, leading to acute and chronic inflammation in various models of gut infection and colitis. Additionally, this review focuses on type 17 immunity interconnecting multiple organs in autoimmune conditions, with a particular emphasis on the pathogenesis of autoimmune arthritis and neuroinflammation driven by T cells primed within the gut microenvironment.

Closed-loop bowel obstruction and contained perforation secondary to acute on chronic jejunal diverticulitis is rare and should be included in the differential diagnosis of acute abdomen. The association between polymyalgia rheumatica and diverticular disease requires further research but may prompt clinicians to consider appropriate therapies in patients with both diseases.

Jejunal diverticulosis is a sac-like outpouching of the intestinal wall that can cause complications such as diverticulitis, obstruction, abscess, perforation, or fistula formation. Complicated jejunal diverticulosis may present with acute abdomen and nonspecific symptoms which can lead to misdiagnosis and delayed treatment. A 76-year-old male with a remote history of polymyalgia rheumatica (PMR) presented with sudden onset abdominal pain, fever, nausea, vomiting, and inability to pass flatus. Physical exam revealed a distended and diffusely tender abdomen with signs of peritonitis. Laboratory test results were significant for neutrophil-dominant leukocytosis and elevated inflammatory markers. CT scan of the abdomen with IV contrast revealed a contained perforation and a closed-loop small bowel obstruction in the mid-abdomen. The patient underwent emergent exploratory laparotomy and resection of 100 cm of mid-jejunum which was found to have numerous diverticula surrounding the closed-loop obstruction and contained perforation. Pathology findings showed evidence of acute on chronic jejunal diverticulitis. Jejunal diverticulosis with complications may present with an acute abdomen and peritonitis. Closed-loop bowel obstruction and contained perforation secondary to acute on chronic jejunal diverticulitis is uncommonly thought of and should be considered in the differential diagnosis. Additionally, the association between PMR and diverticular disease is notable. While the patient had a remote history but no active PMR on presentation, studies suggest a possible association between gut inflammation and rheumatologic disease. This association should prompt clinicians to consider appropriate therapies and bear in mind the potential risk for diverticular perforation if glucocorticoids are given to treat PMR. Jejunal diverticulosis with multiple complications such as closed-loop bowel obstruction and contained perforation secondary to acute on chronic jejunal diverticulitis is rare and may present with an acute abdomen and nonspecific symptoms. Including rare pathologies as such in the differential diagnosis may prevent misdiagnosis and delayed treatment. While further investigation is needed, the association between diverticulosis and PMR is noteworthy as patients who present with both diseases would require mindful management due to the potential risk of diverticular perforation after treatment with steroids.

Inflammatory bowel disease (IBD)-related arthritis is recognized as the most prevalent extraintestinal manifestation (EIM) of IBD. The objective of this study was to determine the prevalence and characteristics of undiagnosed IBD-related arthritis and to compare two screening questionnaires, DETection of Arthritis in Inflammatory boweL diseases (DETAIL) and IBd Identification of Spondyloarthritis Questionnaire (IBIS-q), for early disease detection.

Between April and October 2023, both the DETAIL and IBIS-q questionnaires were administered to consecutive IBD outpatients visiting the University Hospital of Udine, Italy. During routine gastroenterology evaluations, patients aged > 18 years with Crohn's disease (CD) or ulcerative colitis (UC) were requested to complete both questionnaires. Subsequently, all patients who completed the questionnaires underwent a blinded rheumatological evaluation within 2 weeks. Patients with a previous diagnosis of IBD-related SpA were then excluded.

Overall, 203 patients were enrolled, of whom 26 were excluded because of a prior diagnosis of inflammatory arthritis. Among the remaining 177 patients, 10/177 (5.6%) received a new diagnosis of IBD-related arthritis. The median duration of symptoms before diagnosis was 4 (IQR 1.8-10.5) months. Imaging-confirmed enthesitis was the predominant pattern in 8 out 10 cases (80%, with 8 out 8 lacking concomitant peripheral arthritis), axial involvement in 1 out 10 cases (10%), and peripheral arthritis in 1 out 10 cases (10%). The DETAIL questionnaire exhibited higher specificity, but lower sensitivity compared to the IBIS-q, with a sensitivity of 40.0% (12.2-73.8) and specificity of 84.4% (78.0-89.6) versus a sensitivity of 70.0% (34.8-93.3) and specificity of 74.3% (66.9-80.7). Both questionnaires performed less effectively than in other studies.

This study highlights a significant proportion of undiagnosed IBD-related arthritis (5.6%). Enthesitis emerged as the predominant pattern of newly diagnosed arthritis in our cohort, likely due to the recent onset of symptoms. Our study underscores the importance of entheseal involvement in early IBD-related arthritis and the importance of incorporating entheseal involvement into screening questionnaires.

This study aimed to determine the effect of the probiotic Saccharomyces boulardii (S. boulardii) in patients with knee osteoarthritis (KOA).

In this study, 70 patients with KOA were recruited via outpatient clinics between 2020 and 2021 and randomly assigned to receive probiotics or placebo supplements for 12 weeks. The primary outcome was a change in pain intensity according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.

Sixty-three patients completed the trial. A linear mixed analysis of covariance (ANCOVA) model analysis showed that probiotic was better than placebo in decreasing the pain intensity measured by visual analogue scale (VAS) [-2.11 (-2.59, -1.62) in probiotic group and -0.90 (-1.32, -0.48) in placebo group, p = 0.002] and WOMAC pain score [-3.57 (-4.66, -2.49) in probiotic group and -1.43 (-2.33, -0.53) in placebo group, p < 0.001]. The daily intake of acetaminophen for pain management significantly decreased in the probiotic group [-267.18 (-400.47, -133.89) mg, p < 0.001] that was significantly better than placebo (p = 0.006). Probiotic significantly decreased the serum levels of high-sensitivity C-reactive protein (hs-CRP) inflammatory index [-2.72 (-3.24, -2.20) µg/ml] and malondialdehyde (MDA) oxidative stress index [-1.61 (-2.11, -1.11) nmol/ml] compared to the placebo (p = 0.002 and p < 0.001, respectively). Probiotic was better than placebo in increasing the scores of role disorder due to physical health (p = 0.023), pain (p = 0.048) and physical health (p = 0.031).

Probiotic S. boulardii supplementation in patients with KOA significantly improved pain intensity, some dimensions of QoL, and inflammatory and oxidative stress biomarkers with no severe side effects.

Registered on the Iranian clinical trial website ( http://www.irct.ir : IRCT20161022030424N4) on 2019-09-02.

Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2-3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA.

To investigate the psoriatic disease risk among patients with previous appendicitis.

This study was a nationwide population-based case-control study about the association between the psoriatic disease risk among patients with a history of appendicitis in Taiwan. The study population consisted of newly diagnosed psoriatic disease with at least two outpatient visits, and the control group included those patients without psoriatic disease at the same index date. Patients with a previous diagnosis of appendicitis or who underwent appendectomy surgery prior to their psoriatic disease diagnosis were recorded. The odds ratio of psoriatic disease diagnosis in the two groups with and without a history of appendicitis were analyzed and compared.

A total of 48 894 individuals diagnosed with psoriatic disease were matched with 292 656 controls by age and gender. Notably, the proportion of patients with a history of appendicitis or primary appendectomy was significantly elevated among those with psoriatic disease compared with the control cohort (both p < .05). On average, the occurrence of appendicitis preceded the index date by 3.3 ± 2.3 years. Multivariate analysis revealed a heightened incidence rate of psoriatic disease in patients previously diagnosed with appendicitis, periodontal disease, Charlson comorbidity index score (CCIS) ≧1, and ill-defined intestinal infections. This association persisted after adjusting for confounding factors, such as periodontal disease, CCIS, Salmonella, and ill-defined intestinal infections. The odds ratios for psoriatic disease in individuals with a history of appendicitis, periodontal disease, CCIS ≧1, and ill-defined intestinal infections were 1.16, 1.008, 1.69, and 1.23, respectively, with corresponding 95% confidence intervals of 1.03-1.31, 1.05-1.11, 1.65-1.74, and 1.20-1.26. These findings underscore the independent association between appendicitis and subsequent development of psoriatic disease, even after adjusting for relevant comorbidities and potential confounders.

Our research illustrates that appendicitis is associated with an increased likelihood of developing a psoriatic disease, despite several limitations. These limitations encompass variables such as dietary and smoking habits, alongside other potential confounding factors that were not fully considered. Moreover, inherent biases in utilizing national health insurance data, such as the absence of laboratory information, as well as the constraints inherent in a retrospective study design, should be acknowledged.

A significant number of patients with axial spondyloarthritis (axSpA) do not respond to biological therapy. Therefore, we decided to investigate the specificity of this group of patients and, in particular, whether haptoglobin (Hp), its polymorphism and zonulin, in addition to other clinical features, are predictors of poor response to biological treatment.

48 patients with axSpA who were unsuccessfully treated with standard drugs were converted to biological treatment, and from this time on, a 12-week follow-up was started to assess the failure of biological treatment (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decrease < 2 points). Predictors of treatment failure were identified using logistic regression analysis.

21% of subjects had biological treatment failure. Patients who had a higher zonulin level, a history of frequent infections, were older, had inflammatory bowel disease (IBD), had a lower Hp level at the time of inclusion in biological therapy showed an increased risk of treatment failure.

The results of the study support the hypothesis that the effectiveness of biological treatment of axSpA is limited by changed microbiota and intestinal epithelial barrier dysfunction, as an increased risk of biological treatment failure was observed in patients who were older, had higher zonulin level, IBD and repeated courses of antibiotics due to frequent infections. Therefore, starting biological treatment should be followed by reducing intestinal permeability and regulating the disturbed gut microbiome.

Early periprosthetic joint infection constitutes one of the most frightening complications of joint replacement. Recently, some evidence has highlighted the potential link between dysregulation of the gut microbiota and degenerative diseases of joints. It has been hypothesized that microbiome dysbiosis may increase the risk of periprosthetic joint infection by facilitating bacterial translocation from these sites to the bloodstream or by impairing local or systemic immune responses. Although the processes tying the gut microbiome to infection susceptibility are still unknown, new research suggests that the presurgical gut microbiota-a previously unconsidered component-may influence the patient's ability to resist infection. Exploring the potential impact of the microbiome on periprosthetic joint infections may therefore bring new insights into the pathogenesis and therapy of these disorders. For a successful therapy, a proper surgical procedure in conjunction with an antibacterial concept is essential. As per the surgical approach, different treatment strategies include surgical irrigation, debridement, antibiotic therapy, and implant retention with or without polyethylene exchange. Other alternatives could be one-stage or two-stage revisions surgery. Interventions that either directly target gut microbes as well as interventions that modify the composition and/or function of the commensal microbes represent an innovative and potentially successful field to be explored. In recent times, innovative therapeutic methods have arisen in the realm of microbiome restoration and the management of gut-related ailments. These progressive approaches offer fresh perspectives on tackling intricate microbial imbalances in the gastrointestinal tract. These emerging therapies signify a shift towards more precise and individualized approaches to microbiome restoration and the management of gut-related disorders. Once a more advanced knowledge of the pathways linking the gut microbiota to musculoskeletal tissues is gained, relevant microbiome-based therapies can be developed. If dysbiosis is proven to be a significant contributor, developing treatments for dysbiosis may represent a new frontier in the prevention of periprosthetic joint infections.

We aimed to study trabecular bone score (TBS) association with disease parameters and vertebral fractures (VFs) in patients with axial spondyloarthritis.

Patients diagnosed with axial spondyloarthritis were included in this cross-sectional study. Dual-energy X-ray absorptiometry was used to measure BMD in the lumbar spine and TBS. Low TBS was defined as ≤1.31. The association between TBS and disease parameters including Ankylosing Spondylitis Disease Activity Score (ASDAS), BASDAI, BASFI and BASMI was studied using logistic regressions.

Our study included 56 patients, with a mean age of 38.9 ± 13.5 years and a mean disease duration of 12.7 ± 7.7 years. Patients with low TBS were significantly older and had higher waist circumference and body mass index. These patients also showed greater clinical activity, as evidenced by higher ASDAS-CRP, BASFI and BASMI scores (P < 0.05). In multivariate logistic regression, low TBS was associated with all disease parameters, except for BASMI: BASDAI (OR [95% CI] = 3.68 [1.48-9.19], P = 0.005), ASDAS-CRP (OR [95% CI] = 2.92 [1.20-7.10], P = 0.018), BASFI (OR [95% CI] = 1.04 [1.01-1.08], P = 0.018), BASMI (OR [95% CI] = 1.36 [0.99-1.87], P = 0.062). However, no association was observed between TBS and VFs.

TBS was associated with active spondyloarthritis, suggesting increased bone fragility in these patients. However, TBS failed to demonstrate an association with VFs.

Inflammatory bowel disease (IBD) is strongly associated with Spondylarthritis (SpA), but the causal relationship remains unclear. This study explores the causal associations between IBD (Crohn's disease [CD] and ulcerative colitis [UC]) and several common subtypes of SpA (Ankylosing Spondylitis [AS], Psoriatic Arthritis [PsA], and Reactive Arthritis [ReA]), using bidirectional two-sample Mendelian randomization (TSMR).

The causal effects of genetically predicted IBD on AS, PsA, and ReA were firstly investigated in this forward study. The causal effects from AS, PsA, and ReA on IBD were analyzed in the reverse MR. Inverse variance weighted, weighted median, and MR-Egger were applied in the MR analyses. The pleiotropic effects, heterogeneity, and leave-one-out sensitivity analysis were also evaluated.

The forward MR analysis demonstrated that IBD increased risk for AS (OR:1.278; P = 1.273 × 10-5), PsA (OR:1.192; P = 1.690 × 10-5), and ReA (OR:1.106; P = 1.524 × 10-3). Among them, CD increased risk of AS (OR:1.196; P = 3.424 × 10-4), PsA (OR:1.101; P = 1.537 × 10-3), ReA (OR:1.079; P = 6.321 × 10-3) whereas UC increased risk of AS (OR:1.166; P = 2.727 × 10-2), PsA (OR:1.110; P = 1.944 × 10-2), and ReA (OR:1.091; P = 1.768 × 10-2). The reverse-direction MR disclosed no notable association; neither was any evidence of pleiotropy detected.

Our study verifies a causal effect of IBD to AS, PsA as well as ReA, but not vice versa. This might bring new insights for the management of IBD and SpA in clinical practice.

Most host-microbiota interactions occur within the intestinal barrier, which is essential for separating the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. Gut inflammation allows pathogenic bacteria to enter the blood stream, forming immune complexes which may deposit on organs. Despite increased circulating immune complexes (CICs) in patients with inflammatory bowel disease (IBD) and discussions among IBD experts regarding their potential pathogenic role in extra-intestinal manifestations, this phenomenon is overlooked because definitive evidence demonstrating CIC-induced extra-intestinal manifestations in IBD animal models is lacking. However, clinical observations of elevated CICs in newly diagnosed, untreated patients with IBD have reignited research into their potential pathogenic implications. Musculoskeletal symptoms are the most prevalent extra-intestinal IBD manifestations. CICs are pivotal in various arthritis forms, including reactive, rheumatoid, and Lyme arthritis and systemic lupus erythematosus. Research indicates that intestinal barrier restoration during the pre-phase of arthritis could inhibit arthritis development. In the absence of animal models supporting extra-intestinal IBD manifestations, this paper aims to comprehensively explore the relationship between CICs and arthritis onset via a multifaceted analysis to offer a fresh perspective for further investigation and provide novel insights into the interplay between CICs and arthritis development in IBD.

Dysregulation of the gut microbiota and their metabolites is involved in the pathogenic process of intestinal diseases, and several pieces of evidence within the current literature have also highlighted a possible connection between the gut microbiota and the unfolding of inflammatory pathologies of the joints. This dysregulation is defined as the "gut-joint axis" and is based on the joint-gut interaction. It is widely recognized that the microbiota of the gut produce a variety of compounds, including enzymes, short-chain fatty acids, and metabolites. As a consequence, these proinflammatory compounds that bacteria produce, such as that of lipopolysaccharide, move from the "leaky gut" to the bloodstream, thereby leading to systemic inflammation which then reaches the joints, with consequences such as osteoarthritis, rheumatoid arthritis, and spondylarthritis. In this state-of-the-art research, the authors describe the connections between gut dysbiosis and osteoarthritis, rheumatoid arthritis, and spondylarthritis. Moreover, the diagnostic tools, outcome measures, and treatment options are elucidated. There is accumulating proof suggesting that the microbiota of the gut play an important part not only in immune-mediated, metabolic, and neurological illnesses but also in inflammatory joints. According to the authors, future studies should concentrate on developing innovative microbiota-targeted treatments and their effects on joint pathology as well as on organizing screening protocols to predict the onset of inflammatory joint disease based on gut dysbiosis.

According to the Assessment of SpondyloArthritis International Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axial spondyloarthritis (axSpA), patients should undergo at least two courses of non-steroidal anti-inflammatory drugs (NSAIDs) therapy. In our study, we enrolled axSpA patients both at onset and in a flare who had already been treated with NSAIDs ineffectively. Subsequently, according to the recommendations, they received modified NSAID treatment as another attempt to the first-line drug therapy and were monitored from there. We aimed to identify risk factors for treatment failure after 4 weeks (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4) especially amongst zonulin and haptoglobin concentrations, and haptoglobin polymorphism. Treatment failure was observed in 71% of patients, and the following variables were contributed for occurrence of this state: higher zonulin levels, ankylosing spondylitis, X-ray sacroiliitis, magnetic resonance imaging sacroiliitis, long duration of symptoms, high BASDAI, and high value of spinal pain intensity on visual analogue scale. In addition, the following positive correlations were found: haptoglobin concentration with C-reactive protein (r = 0.56; p = 0.0004), and erythrocyte sedimentation rate (r = 0.62; p < 0.0001), as well as between zonulin levels and white blood count (r = 0.5; p = 0.0003). The results of the study presented the identified factors related to the standard treatment failure in axSpA, amongst them zonulin levels. They might be applied to point out the patients for whom the search for a more appropriate method of treatment should be considered.

Despite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear.

Gut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships.

We identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29-2.69); p = 8.63E-04). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47-0.93); p = 1.81E-02) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50-0.97); p = 3.00E-02). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00-1.51); p = 4.94E-02) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35-0.88); p = 1.14E-02). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota.

Our MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.

The role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease combined with axial spondyloarthritis (axSpA) is gaining widespread interest.

This study was conducted to investigate the clinical and fecal microbiota characteristics of patients with both ulcerative colitis (UC) and axSpA.

Clinical data were collected from patients with UC. Patients were divided into the axSpA and non-axSpA groups according to human leukocyte antigen-B27 serology and sacroiliac joint imaging results. We obtained fecal specimens from 14 axSpA and 26 non-axSpA patients. All samples underwent 16S ribosomal DNA sequencing.

Seventy-three patients with UC were included in this study, and the axSpA incidence was 19.2%. This incidence was significantly higher in patients with C-reactive protein > 10 mg/L. Firmicutes and Faecalibacterium abundances were decreased, and Proteobacteria and Escherichia_Shigella abundances were increased in the axSpA group compared with those of the non-axSpA group. Indicator analysis showed that Escherichia_Shigella was more likely to be an indicator species of axSpA. Additionally, many biosynthetic and metabolic pathways, including glutathione metabolism, fatty acid degradation, geraniol degradation, and biosynthesis of siderophore group nonribosomal peptides, were upregulated in the axSpA group.

Patients with UC have a high axSpA incidence, which may be related to the relative abundances of Escherichia_Shigella in these patients. The abundances of various biosynthetic and metabolic pathways of the fecal flora were upregulated in patients with axSpA.

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

Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear. Here, we find that systemic single injections of Akkermansia muciniphila (A. m.), a mucin-degrading bacterium, rapidly activate BM myelopoiesis and slow but long-lasting hepato-splenomegaly, characterized by the expansion and differentiation of functional HSPCs, which we term delayed EMH. Mechanistically, delayed EMH triggered by A. m. is mediated entirely by the MYD88/TRIF innate immune signaling pathway, which persistently stimulates splenic myeloid cells to secrete interleukin (IL)-1α, and in turn, activates IL-1 receptor (IL-1R)-expressing splenic HSPCs. Genetic deletion of Toll-like receptor-2 and -4 (TLR2/4) or IL-1α partially diminishes A. m.-induced delayed EMH, while inhibition of both pathways alleviates splenomegaly and EMH. Our results demonstrate that cooperative IL-1R- and TLR-mediated signals regulate commensal bacteria-driven EMH, which might be relevant for certain autoimmune disorders.

The gut microbiome represents a potential promising therapeutic target for autoimmune diseases. This review summarizes the current knowledge on the links between the gut microbiome and several autoimmune rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) spondyloarthropathies (SpA), Sjogren's syndrome (SS), and systemic sclerosis (SSc). Evidence from studies of RA and SLE patients suggests that alterations in the gut microbiome composition and function contribute to disease development and progression through increased gut permeability, with microbes and microbial metabolites driving an excessive systemic activation of the immune system. Also, there is growing evidence that gut dysbiosis and subsequent immune cell activation may contribute to disease pathogenesis in SpA and SS. For SSc, there are fewer, but these are still informative, reports on alterations in the gut microbiome. In general, the complex interplay between the microbiome and the immune system is still not fully understood. Here we discuss the current knowledge of the link between the gut microbiome and autoimmune rheumatic diseases, highlighting potentially fertile areas for future research and make considerations on the potential benefits of strategies that restore gut microbiome homeostasis.

Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients.

To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients.

The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%.

From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups.

No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection.

This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).

This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1 H Nuclear Magnetic Resonance.

Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).

Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.