Objective. Systemic sclerosis (SSc) gastrointestinal (GI) disease is heterogeneous in presentation, with individual symptoms lacking specificity for specific anatomical and functional abnormalities. We used factor analysis to investigate whether latent subgroups of SSc-GI symptoms can be detected. Methods. Using the University of California, Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal 2.0 (GIT 2.0) questionnaire data from 773 Australian Scleroderma Cohort Study participants, we performed a factor analysis of, firstly, GIT 2.0 domains scores, and then individual GIT 2.0 question responses to identify latent factors. A subsequent cluster analysis was performed to explore whether clinically definable SSc phenotypes were associated with specific GI symptoms. Results. SSc-GI symptoms were highly correlated. Factor analysis of individual GIT 2.0 question responses revealed 4 latent factors within the dataset that could be clinically described as upper GI tract symptoms, bloating, diarrhea and incontinence, and constipation. Cluster analysis revealed 2 patient clusters, distinguished by disease duration and severity of GI manifestations. Anticentromere antibodies and pulmonary arterial hypertension were more common in participants with severe GI disease. Conclusion. Despite the high correlation between GI manifestations, it is possible to detect subgroups of SSc-GI symptoms. Improved understanding of these subgroups of SSc-GI disease may advance the discovery of targeted interventions to improve the daily function and quality of life of those living with SSc.

Background:Gastro-esophageal reflux disease (GERD) occurs in most (~75%) patients with systemic sclerosis (SSc) and significantly impacts quality of life. Current recommendations lack depth and therefore, our aim was to produce practical, consensus-based recommendations for refractory SSc-related GERD. Methods:An international, multidisciplinary Steering Board (SB) was assembled (n=19) consisting of clinicians (rheumatologists, gastroenterologists, GI surgeons), an expert methodologist, and patient representation. After reviewing the latest definitions of GERD and refractory GERD in the published literature, the SB collectively devised a practical definition of SSc refractory-GERD. Initial recommendations were drafted/agreed upon by the SB based on review of the existing guidelines, published literature, and expert opinion. Two online voting rounds were conducted to determine whether items should be accepted, with >75% and >60% SB agreement required for first and second rounds, respectively. Results:There was a good response/completion rate for the initial (74%) and final (84%) voting rounds. The SB agreed on all 36 draft recommendations. The majority (n=34) were approved in the first round. Recommendations were organized according to the following categories: general approach to management (n=5), assessment (n=6), non-pharmacological (n=2) and pharmacological (n=10) management, endoscopic and surgical treatment (n=3), and special circumstances, including refractory GERD and SSc-ILD (n=3), myositis and SSc CTD-overlap (n=3) and peri-lung transplant (n=4). Conclusion:The group of experts has drafted extended and practical recommendations for the management of SSc refractory-GERD. The necessity of a structured approach and a patient assessment is highlighted in order to provide a multi-disciplinary approach to the tailored choice of the treatment. Our work also has also identified significant unmet needs and has provided a research agenda to advance the field.

OBJECTIVE:This study aims to identify factors associated with patient global assessment (PtGA) and physician global assessment (PhGA) and discordance between them in systemic sclerosis (SSc). METHODS:Data from adults with early SSc (<5 years) from the Collaborative National Quality and Efficacy Registry were included. PtGA and PhGA (0-10 scale), clinical evaluations, and patient-reported outcomes (PROs) were collected every six months. Multivariable mixed-effects linear regression identified factors associated with PtGA and PhGA using (1) clinical variables and (2) clinical variables plus PROs. Relative weight analysis (RWA) determined the relative importance of each variable. Discordance (≥2 points between PtGA and PhGA) was assessed using multinomial mixed-effects logistic regression. RESULTS:Among 956 patients (83% women, 33% limited disease), mean PtGA and PhGA at enrollment were 4.2 (SD 2.6) and 3.4 (SD 2.0), respectively (P < 0.001). RWA of clinical variables identified modified Rodnan skin score (mRSS) and New York Heart Association (NYHA) functional class as most influential for both global assessments. After including PROs, PtGA was most influenced by measures of pain, skin symptoms, and physical function. Discordance occurred in 53% of patients (35% PtGA worse, 18% PhGA worse). Worse PtGA was associated with higher overall pain and discomfort. Worse PhGA was associated with higher mRSS, worse NYHA class, higher pain interference, and lower diffusing capacity of the lung. CONCLUSION:Discordance between PtGA and PhGA occurs commonly, highlighting the need for comprehensive symptom management and measurement of disease burden in this complex disease. In SSc, differences in PtGA and PhGA reflect dissimilar weighting of data elements.

PURPOSE OF THE REVIEW:Respiratory disease is a major cause of morbidity and mortality for patients with systemic autoimmune diseases. Chronic exertional fatigue, breathlessness, and cough all cause significant impairment of quality of life. In this review, we summarize the major respiratory complications of systemic autoimmune diseases and consider the evidence supporting the role that palliative care can play in the management of systemic autoimmune disease. RECENT FINDINGS:The symptom burden suffered by patients with systemic autoimmune diseases is equivalent to that of patients with active malignancy. Recent studies have explored how palliative care could be integrated with rheumatology care to improve symptom control and address the high psychosocial burden associated with living with a systemic autoimmune disease. Both rheumatologists and palliative care providers are uncertain as to the role of palliative care in the management of systemic autoimmune diseases, with the optimal model of integrated palliative care yet to be defined. SUMMARY:Emerging evidence supports the acceptability and value of palliative care to patients living with a systemic autoimmune disease and their caregivers. However, there are both patient and physician associated barriers to the integration of palliative care with rheumatology care. Studies are required to demonstrate the efficacy of palliative care in the management of systemic autoimmune diseases.

INTRODUCTION:Our understanding of the pathogenesis of systemic sclerosis-associated gastrointestinal (SSc-GI) disease is limited. This has hindered progress in the management of SSc-GI disease as objective measures to assess the extent of disease and monitor treatment response are lacking. We propose a conceptual model for understanding pathogenic mechanisms of SSc-GI symptoms. A multi-dimensional model of understanding the etiology of symptoms may enable an improved understanding of patients' symptom experience and opportunities for development of therapies. AREAS COVERED:We reviewed literature from the past 5 years pertaining to SSc-GI symptoms and their etiology. When gaps in data were identified, we evaluated research from general gastroenterology and inflammatory bowel disease. We describe evolving concepts of pathologic mechanisms of SSc-GI disease, including motility, the gut-brain axis, diet, the microbiome and pelvic floor dysfunction. EXPERT OPINION:A broad understanding of factors that contribute to symptoms is necessary to understand the experience of SSc-GI disease and develop targeted therapies that modify the SSc-GI disease course. Due to a lack of objective clinical outcome measures in SSc-GI disease, qualitative research methodologies are essential for deepening our understanding of these patient experiences and developing new outcome measures to enable trials to establish an evidence-based approach to SSc-GI disease.

Background:Fecal incontinence (FI) affects up to 50% of patients with systemic sclerosis (SSc), significantly impairing quality of life and daily functioning. Despite its prevalence, patients may not disclose their symptoms and there is limited guidance on evaluation and management. Given the complexity of SSc and delays in gastroenterology referrals, rheumatologists often initiate care. To address this gap, an expert panel was convened to develop practical, consensus-based recommendations for assessing and managing SSc-FI. Methods:An international Steering Board (n=19) was assembled under the auspices of the World Scleroderma Foundation GI ad hoc committee, including clinicians from rheumatology, gastroenterology, and GI surgery, as well as a methodology expert and a patient representative. A working definition of SSc-FI was established. Draft recommendations were developed through a literature review and expert consensus. Two rounds of online voting were conducted, requiring ≥75% agreement in round one and ≥60% in round two for inclusion. Results:In the first and second voting rounds, participation rates were 63.2% and 84.2%, respectively. All 22 draft recommendations were approved, with most (21) reaching consensus in the first round. Recommendations span five domains: general management approach (n=3); clinical assessment and non-pharmacological interventions (n=7 and n=3, respectively); management of FI in the context of diarrhea (n=5); and alternative interventions and strategies (n=4). Conclusion:These are the first practical recommendations for managing SSc-related FI. They emphasize a structured, multidisciplinary approach to care, highlight unmet clinical needs, and lay the foundation for a research agenda to advance the understanding and treatment of this underrecognized complication in patients with SSc.

OBJECTIVE:We evaluated baseline characteristics, treatment patterns, and outcomes in patients with systemic autoimmune rheumatic disease-associated progressive pulmonary fibrosis (SARD-PPF) and evaluated whether outcomes differed by SARD subtype. METHODS:The ILD-PRO Registry is a prospective multicenter US registry of patients with PPF. Eligible participants had an ILD other than idiopathic pulmonary fibrosis with reticulation and traction bronchiectasis on high-resolution computed tomography and/or lung biopsy, and met criteria for PPF within the prior 24 months. Among patients with SARD-PPF, we described baseline characteristics and evaluated associations between SARD subtype and clinical outcomes. RESULTS:Among 585 patients with SARD-PPF, physiologic impairment at enrollment was substantial (median FVC 64.5% predicted; median DLco 38.0% predicted); 39.2% used supplemental oxygen, 73.9% were receiving immunomodulatory therapy, and 22.6% were taking nintedanib. By 24 months, 31.3%-62.1% of patients experienced ILD progression across SARD subtypes, and 9.3%-37.6% experienced death or lung transplant. Rheumatoid arthritis-PPF showed the highest unadjusted probability of ILD progression; however, no significant subtype-associated differences were observed in analyses adjusted for age, sex, and/or baseline FVC % predicted. CONCLUSION:In a large prospective multicenter US cohort, SARD-PPF was characterized by advanced physiologic impairment, high treatment burden, and high risk for further progression and death or lung transplant. After accounting for demographic factors and baseline severity, outcomes were broadly similar across SARD diagnoses, supporting phenotype-focused risk stratification and underscoring the need for systematic monitoring and timely optimization of management for SARD-ILD.

Sex differences in the prevalence, clinical phenotypes and therapeutic responses of rheumatic diseases have been recognized for decades, but the underlying mechanisms remain largely unknown. Accumulating evidence highlights the critical roles of both immune and non-immune cells in disease pathogenesis and the influence of sex hormones on cellular function. In addition, factors such as sex chromosomes, hormonal regulation, antiviral immune response, the gut microbiome and genetic and epigenetic variation probably contribute to the divergent features of rheumatic diseases between women and men. A deeper understanding of these intersecting pathways might uncover novel therapeutic targets. Thus far, treatment strategies for rheumatic diseases largely focus on immunomodulation; however, elucidating the biological basis of sex differences could enable the development of preventative therapies that target hormonal pathways and the gut microbiome, with the potential to avert both the onset and progression of these debilitating diseases to improve health for all patients.

PURPOSE OF REVIEW:A central challenge in systemic sclerosis (SSc) is the inability to distinguish active, potentially reversible disease, from damage, irreversible fibrosis. Current imaging modalities, including high-resolution computed tomography (HRCT) and echocardiography, predominantly capture structural damage and cannot resolve this distinction. This review outlines next generation imaging modalities for SSc with focus on quantitative machine learning algorithms and molecular imaging. RECENT FINDINGS:The unifying advance across organ systems is a shift from documenting damage to measuring disease activity directly. Machine-learning-derived quantitative HRCT detects radiological patterns of ILD sensitive to change in SSc-associated interstitial lung disease. Parametric cardiac magnetic resonance mapping resolves diffuse interstitial fibrosis missed by late gadolinium enhancement. Fibroblast activation protein inhibitor PET (FAPI-PET) visualizes active fibrogenesis in lung and myocardium, identifying biologically active disease even before structural distortion occurs. [18F]Sodium fluoride PET detects metabolically active calcinosis. High-frequency ultrasound, elastography, and optical coherence tomography (OCT)-angiography extend objective assessment of cutaneous and microvascular involvement. SUMMARY:Emerging imaging modalities in SSc may enable earlier detection of active disease amenable to treatment modification and yield more sensitive endpoints for SSc clinical trials.

In the past 3 years key recommendations for the management of systemic sclerosis (SSc) have been published, including updated EULAR recommendations and British Society for Rheumatology (BSR) guidelines. These recommendations are generally aligned but also reflect differences in the methodology and scope of the responsible organizations. For both EULAR and BSR, the methodology is robust and aligns with recommendations and guidelines developed for other rheumatic conditions and produced by other specialist societies. Advances in treatment and a growing evidence base for management of interstitial lung disease (ILD), a frequent complication of SSc, have informed additional relevant recommendations that include SSc-ILD. Some of these cover a broad range of ILDs that occur across systemic autoimmune rheumatic diseases, including those developed by the ACR-American College of Chest Physicians and the 2025 European Respiratory Society-EULAR clinical-practice guidelines. The American Thoracic Society has also developed recommendations for SSc-ILD. Taken together, a comparison of these published guidelines provides an overview of best practice evidence-based management that is supported by expert opinion and relevant stakeholders. By considering the overlap and similarity in recommendations and highlighting differences in approach and scope, this article helps readers to navigate an evolving treatment landscape of SSc.

Objective. Dysregulated collagen turnover is implicated in systemic sclerosis (SSc) pathogenesis. We evaluated collagen turnover biomarkers in relation to the severity of fibrotic manifestations, key cytokines, and progression in SSc. Methods. Baseline and 6-month serum samples of patients with early SSc in the Collaborative National Quality and Efficacy Registry (CONQUER) cohort were analyzed for type III (pro-collagen III [PRO-C3] and collagen III M [C3M]) and type VI (pro-collagen VI [PRO-C6] and collagen VIM [C6M]) collagen turnover biomarkers, as well as C-reactive protein (CRP), interleukin 6 (IL-6), and interferon (IFN)-inducible proteins. The modified Rodnan skin score and % predicted forced vital capacity (FVC%) served as surrogate markers of disease severity. Results. A total of 222 patients were included. PRO-C3 (P < 0.001) and PRO-C6 (P < 0.001) concentrations were higher in patients with diffuse disease, whereas C6M (P = 0.04) was higher in those with interstitial lung disease. Baseline PRO-C3 (P < 0.001) and PRO-C6 (P < 0.001) positively correlated with mRSS, whereas C3M (P = 0.03) and C6M (P = 0.01) negatively correlated with FVC%, although the magnitude of the observed correlations was in the weak range (rs < 0.4). Collagen biomarker concentrations positively correlated with CRP, IL-6, and IFN-inducible proteins at baseline. Although changes in CRP positively correlated with changes in collagen degradation protein levels (C3M and C6M), they did not correlate with changes in collagen formation protein levels (PRO-C3 and PRO-C6). In contrast, changes in IFN score showed the highest correlation with changes in PRO-C6. Conclusion. PRO-C3 and PRO-C6 correlated with skin disease severity, whereas C3M and C6M correlated with lung disease severity. Collagen turnover biomarkers correlated with CRP, IL-6, and IFN-inducible proteins, providing support for the link between inflammation and fibrosis in SSc.

OBJECTIVE:Pulmonary complications, including interstitial lung disease (ILD), are common and contribute to morbidity and mortality in mixed connective tissue disease (MCTD). However, risk factors for ILD in MCTD are poorly understood, which can hinder early detection of this fatal complication. The purpose of this study was to identify predictors of ILD presence in MCTD using structured electronic health record (EHR) data. METHODS:We performed a retrospective EHR-based investigation of adults with MCTD evaluated at a large urban academic medical center between 2014 and 2026. Patients were identified using an adapted Kasukawa classification algorithm. Univariable and multivariable logistic regression were used to assess associations between clinical features and ILD. Cox proportional hazards models with time-dependent ILD status were used to examine mortality. A prespecified sensitivity analysis was performed using a more restrictive cohort definition. RESULTS:Among 120 patients, 61 (50.8%) had ILD. In multivariable logistic regression, pulmonary hypertension (PH) was independently associated with ILD (OR 5.10, 95% CI 1.91-13.63, p = 0.001). Age 55-74 years was independently associated with ILD (OR 7.61, 95% CI 1.74-33.33, p = 0.007). Gastroesophageal reflux disease (GERD) was associated with higher odds of ILD, although the association did not reach statistical significance after adjustment (OR 3.16, 95% CI 0.92-10.79, p = 0.067). In the survival analysis (n = 120, 11 deaths), the time-dependent hazard ratio for ILD was 2.57 (95% CI 0.74-8.94, p = 0.137); the age-adjusted HR was 2.60 (95% CI 0.75-9.03, p = 0.134). CONCLUSION:ILD affected roughly half of patients with MCTD in this EHR-based cohort. PH and older age were independently associated with ILD, suggesting that patients with these features may warrant heightened pulmonary surveillance. Survival analyses were hypothesis-generating, with ILD associated with numerically higher mortality that did not reach statistical significance. Structured EHR methods can delineate real-world disease patterns in rare systemic autoimmune disease like MCTD. Standardized classification and routine pulmonary screening may enable earlier recognition and targeted intervention.

TOPIC IMPORTANCE:Interstitial lung disease encompasses > 200 disorders characterized by lung parenchymal inflammation and fibrosis, presenting significant diagnostic challenges that often require invasive procedures with substantial morbidity and mortality risks. Diagnostic approaches have traditionally relied on surgical lung biopsy for definitive histopathologic evaluation, a procedure carrying a 1.7% to 3.6% mortality rate; however, its use has declined recently. Bronchoscopy offers a safer alternative that provides direct access to the lung microenvironment through bronchoalveolar lavage, tissue sampling, and airway visualization. REVIEW FINDINGS:Traditional bronchoscopic applications include cellular analysis of bronchoalveolar lavage fluid, which shows promise in differentiating hypersensitivity pneumonitis from idiopathic pulmonary fibrosis through lymphocyte percentages; however, limitations in sensitivity and specificity persist. Transbronchial lung cryobiopsy has emerged as a safer tissue sampling method with 0.0% to 0.3% mortality compared with surgical approaches, albeit with reduced diagnostic yield. Novel genomic classifiers using RNA sequencing from transbronchial biopsies demonstrate high specificity (92%) for identifying usual interstitial pneumonia patterns; however, sensitivity remains limited (68%). Advanced technologies including systems biology approaches through proteomics and metabolomics of bronchoalveolar lavage fluid reveal distinct molecular endotypes with differential survival trajectories, offering potential for personalized treatment strategies. Endobronchial optical coherence tomography provides real-time microscopic visualization with resolution exceeding high-resolution CT scan, enabling accurate diagnosis of fibrotic patterns with excellent concordance to surgical biopsy. SUMMARY:Emerging bronchoscopic technologies could represent a paradigm shift toward precision medicine in interstitial lung disease, potentially transforming diagnostic approaches while maintaining superior safety profiles compared with current invasive standards.

Objectives Physician global assessments (PhyGAs) are commonly performed in randomized controlled trials (RCTs) in SSc. However, there is no single PhyGA applied across RCTs. We performed an exploratory qualitative study to explore perceptions of the PhyGA, its role in RCTs and how physicians perform their own assessment.Methods Participants with expertise in the clinical assessment and, or actively involved in research on SSc were invited to participate. Participants were asked to define disease constructs of activity, damage, severity, and overall health, and to describe how they perform a PhyGA and their perception of what a PhyGA should assess. Interview transcripts were analysed using deductive and inductive thematic analysis.Results Eighteen rheumatologists and one patient research partner were interviewed. Four major themes were identified: (i) physician uncertainty; (ii) variation in the conduct of a PhyGA; (iii) physician efforts to improve PhyGA consistency; (iv) utility of a PhyGA. Most participants felt a PhyGA should assess changeable aspects of SSc, commonly conceived of as disease activity. There was considerable uncertainty about the optimal method for assessing disease activity. Participants were uncertain about their own methods of performing a PhyGA, and variability in the application of the instrument was identified. Despite these limitations, physicians generally agreed that the PhyGA is useful and can assess unquantifiable aspects of SSc.Conclusion We identified significant heterogeneity in the approach to PhyGAs in SSc. This variation was considered a limitation of the PhyGA. Overall, a PhyGA was viewed as a useful instrument that can aid the assessment of treatment response in RCTs.

TOPIC IMPORTANCE:Interstitial lung disease (ILD) affects 40% to 60% of patients with systemic sclerosis (SSc) and represents the leading cause of death. Although treatment options for SSc with ILD remain limited, randomized controlled trials have demonstrated the safety and efficacy of approved and unapproved therapies. However, numerous unanswered questions remain regarding management of SSc with ILD, and 3 recently published clinical practice guidelines highlight the complexity of treating this condition. These guidelines offer distinct and sometimes contrasting views on treatment of SSc with ILD, creating unique challenges for clinicians. The present review aimed to synthesize evidence regarding the management of SSc with ILD with a focus on how to apply the recent guidelines into practice, beginning with screening for disease and extending to the intricate decision-making surrounding treatment. REVIEW FINDINGS:Although an abundance of evidence supports screening all patients with SSc for ILD with high-resolution CT imaging of the chest at the time of diagnosis, emerging evidence underscores the importance of rescreening patients who possess ≥ 1 high-risk factors (male sex, Black race, advanced age, diffuse cutaneous disease, high modified Rodnan skin score, antitopoisomerase antibody positivity, nucleolar antinuclear antibodies, and impaired lung function) or if physiologic changes, new respiratory symptoms, or both attributable to ILD emerge. Patients with established SSc with ILD should be monitored closely for the development of progressive pulmonary fibrosis. The guidelines all recommended, with varying degrees of conditionality, treatment with mycophenolate, tocilizumab, rituximab, cyclophosphamide, and nintedanib. The quality of evidence was rated as low for most therapies, and the only therapy strongly recommended for SSc with ILD was mycophenolate. SUMMARY:This review provides a comprehensive appraisal of current approaches to the diagnosis and treatment of SSc with ILD. It also highlights gaps in knowledge and proposes future opportunities to develop a precision-guided approach to diagnosing and treating SSc with ILD.

Background Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) portends a devastating prognosis for patients, with survival typically being < 5 to 8 years after diagnosis. Limited clinical trial data exist to guide treatment strategies, and the efficacy of current strategies—immunomodulation and antifibrotics—remains uncertain. Large randomized controlled trials are costly, but pragmatic trial designs could reduce expenses. Establishing equipoise and assessing feasibility from both patient and expert perspectives are essential for developing these trials. Research Question What are the perceptions of RA-ILD experts and patients with interstitial lung disease surrounding equipoise, feasibility, and trial design? Study Design and Methods A qualitative study involving a panel of 10 RA-ILD experts and 3 patient panels was conducted. Experts were recruited via snowball sampling, and patient panels included 29 individuals with interstitial lung disease or their caregivers. Discussions were transcribed and analyzed using inductive coding, creating a thematic network based on the Attride-Stirling guidelines. Results Expert themes included variability in treatment strategies, prioritizing patient-reported outcomes and balancing pragmatism with data collection in trial design. Patient themes highlighted outcomes of importance, participation barriers, and the need for patient-centered research. Interpretation Both expert and patient panels endorsed using real-world clinical outcomes and patient-reported outcomes as primary trial end points. Pragmatic trials could reduce costs and expand inclusion criteria, highlighting the potential of patient-centered approaches in RA-ILD research.

BackgroundAlterations in the gastrointestinal (GI) microbiome (i.e., dysbiosis) are a feature of systemic sclerosis (SSc). Diet is a known modifier of the GI microbiome, and ultra-processed food (UPF) consumption has been associated with adverse changes in GI microbial composition. This study aimed to determine whether UPF consumption affects the GI microbiota and GI symptoms in patients with SSc.MethodsAdult SSc patients provided stool samples and completed both the Diet History Questionnaire II (DHQ-2) and the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0). Shotgun metagenomics were performed using the Illumina NovaSeq 6000 with a target depth of 10 million 150x2 sequences per sample. UPF items (N=54) on the DHQ-2 were identified using the NOVA scale of food classification, and UPF intake was calculated as gram-per-week consumption according to patient reported frequency. General linear models were created to identify differentially abundant species based on UPF consumption and to evaluate the relationship between UPF consumption and GI symptoms as measured by the GIT 2.0. These models adjusted for body mass index (BMI), current proton pump inhibitor (PPI) use, current probiotic use, current or prior immunomodulatory therapy, and presence of small intestinal bacterial overgrowth (SIBO).ResultsOf the 65 total SSc patients included, 84.6% were female. The mean age was 53.83 ± 13.19 years, and the mean BMI was 25.25 ± 4.75. The median UPF consumption was 2395.82 g/week. Increased UPF consumption was significantly associated with increased GI symptoms in our multivariate model (β=0.34; p<0.01). Among 257 species analyzed, 5 bacterial species were significantly associated with UPF consumption in the multivariate models, including Limosilactobacillus fermentum (β=0.32; p<0.01) and Faecalicatena fissicatena (β= -0.36; p-value<0.01), while the abundance of 6 bacterial species was significantly associated with GI symptom severity after adjusting for the aforementioned covariates.ConclusionsSSc patients reporting a higher UPF consumption demonstrated alterations in GI microbial composition as well as increased GI symptoms, even after adjusting for factors known to affect the microbiota of patients with SSc. Future studies are needed to determine whether interventions aimed at lowering UPF consumption may improve GI outcomes for patients with SSc.

OBJECTIVE:To evaluate the fecal metabolome in patients with early systemic sclerosis (SSc) compared with unaffected controls and to determine if altered metabolites are associated with specific bacterial genera in patients with early SSc. METHODS:Stool samples and clinical data were collected from 106 patients with early SSc and 79 unaffected control patients. Targeted metabolomics was performed on fecal samples using liquid chromatography mass spectrometry, and 16S ribosomal RNA gene sequencing was used to determine the microbial composition of fecal samples. RESULTS:Compared with unaffected controls, patients with early SSc had higher levels of nicotinamide, 5'-methylthioadenosine, and several short-chain fatty acids (SCFAs) including valeric acid, propionic acid, and caproic acid. Conversely, patients with early SSc had lower levels of xylonic acid, orotate, methionine sulfoxide, and sarcosine. SCFAs were associated with unique bacterial genera, several of which were more abundant in patients with SSc compared with unaffected controls. CONCLUSION:The fecal metabolome is altered in patients with early SSc, with a shift toward increased SCFAs.