Linking serum vitamin D levels with gut microbiota after 1-year lifestyle intervention with Mediterranean diet in patients with obesity and metabolic syndrome: a nested cross-sectional and prospective study.

Vitamin D, microbiota, and the Mediterranean diet (MedDiet) have been the focus of recent research due to their potential role in maintaining overall health. We hypothesize that MedDiet may alter the gut microbiota profile through changes in vitamin D levels. We aimed to investigate changes in gut microbiota and serum vitamin D levels after a MedDiet within a lifestyle intervention. The study included 91 patients with obesity and metabolic syndrome, who were categorized based on their serum vitamin D levels as having either optimal or low 25-hydroxyvitamin D [25(OH)D levels]. The profile of the gut microbiota was analyzed by the 16S rRNA sequencing, inferring its functionality through PICRUsT. Participants underwent a hypocaloric MedDiet and change in their lifestyle for 1 year, and the profile and functionality of their gut microbiota were evaluated by analyzing inter-individual differences in time. At baseline, gut microbiota profiles qualitatively differed between participants with Optimal or Low 25(OH)D levels [Unweighted (p = 0.016)]. Moreover, participants with Optimal 25(OH)D levels showed a higher gut microbiota diversity than those with Low 25(OH)D levels (p < 0.05). The differential analysis of abundance between the Low and Optimal 25(OH)D groups revealed differences in the levels of Bacteroides, Prevotella, and two Clostridiales features. After 1-year dietary intervention, both groups increased their 25(OH)D levels. Furthermore, both groups did not show significant differences in gut microbiota diversity, although the Low 25(OH)D group showed greater improvement in gut microbiota diversity by comparing at baseline and after dietary intervention (p < 0.05). Changes in specific bacterial taxa were observed within each group but did not differ significantly between the groups. Metabolic pathway analysis indicated differences in microbial functions between the groups (p < 0.05). These findings suggest that 25(OH)D status is associated with gut microbiota composition, diversity, and functionality, and lifestyle intervention can modulate both gut microbiota and 25(OH)D levels, potentially influencing metabolic pathways.

Inflammatory Biomarkers in the Diagnosis and Prognosis of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case-control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. The study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR (p = 0.032) and HAQ values (p = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17-5.22]; p = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24-6.78]; p = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00-1.12]; p = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00-1.06]; p = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00-1.00]; p = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07-1.46]; p = 0.004). Our data support that the inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD.

Adiposity is associated with expansion of the genus Dialister in rheumatoid arthritis patients.

OBJECTIVE: To analyze the intestinal microbiota of patients with rheumatoid arthritis (RA) and obesity and a higher percentage of fatty tissue. METHODS: Nested case-control study of 80 RA patients and 80 age and sex-matched controls. Obesity was defined as a body mass index ≥ 30, and body composition using dual-energy x-ray absorptiometry. The gut microbiota was analyzed using 16 S rRNA gene sequencing; bioinformatics analysis was performed using QIIME2 and PICRUSt. Other variables included averaged 28-joint Disease Activity Score (DAS28-ESR), cytokines and adipokines. Two multivariate were constructed with obesity and fat mass index (FMI). RESULTS: Obesity was more frequent in RA patients than in controls (36.3 % vs 25.1 %; p = 0.026), as was a higher FMI value (mean [SE]=11.6 [3.9] vs 10.2 [3.9]; p = 0.032). Alpha and beta diversity analysis revealed differences in gut microbiota between RA patients with and without obesity. Dialister and Odoribacter were more abundant in RA patients with obesity than in RA patients without obesity, while the genus Clostridium was more abundant in RA patients without obesity. The factors associated with obesity in RA patients were age (OR [95 % CI], 1.09 [1.02-1.17]), mean DAS28-ESR (OR [95 % CI], 1.46 [1.12-1.67]), leptin levels (OR [95 % CI], 1.06 [1.01-1.10]), the genus Dialister (OR [95 % CI], 1.03 [1.01-1.07]), and the genus Clostridium (OR [95 % CI], 0.013 [0.00-0.36]). The associations observed for FMI were similar. CONCLUSIONS: In patients with RA, obesity, and a higher percentage of fatty tissue, intestinal microbiota differed from that of controls and of the other patients. The genus Dialister was associated with obesity and FMI.

Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study.

Objectives: To describe the characteristics of patients between late-onset rheumatoid arthritis (LORA) with young-onset (YORA), and analyze their association with cumulative inflammatory burden. Methods: We performed a nested cohort study in a prospective cohort comprising 110 patients with rheumatoid arthritis (RA) and 110 age- and sex-matched controls. The main variable was cumulative inflammatory activity according to the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). High activity was defined as DAS28 ≥ 3.2 and low activity as DAS28 < 3.2. The other variables recorded were inflammatory cytokines, physical function, and comorbid conditions. Two multivariate models were run to identify factors associated with cumulative inflammatory activity. Results: A total of 22/110 patients (20%) met the criteria for LORA (≥ 60 years). Patients with LORA more frequently had comorbid conditions than patients with YORA and controls. Compared with YORA patients, more LORA patients had cumulative high inflammatory activity from onset [13 (59%) vs. 28 (31%); p = 0.018] and high values for CRP (p = 0.039) and IL-6 (p = 0.045). Cumulative high inflammatory activity in patients with RA was associated with LORA [OR (95% CI) 4.69 (1.49-10.71); p = 0.008], smoking [OR (95% CI) 2.07 (1.13-3.78); p = 0.017], anti-citrullinated peptide antibody [OR (95% CI) 3.24 (1.15-9.13); p = 0.025], average Health Assessment Questionnaire (HAQ) score [OR (95% CI) 2.09 (1.03-14.23); p = 0.034], and physical activity [OR (95% CI) 0.99 (0.99-0.99); p = 0.010]. The second model revealed similar associations with inflammatory activity in patients with LORA. Conclusion: Control of inflammation after diagnosis is poorer and comorbidity more frequent in patients with LORA than in YORA patients and healthy controls.

Collinsella is associated with cumulative inflammatory burden in an established rheumatoid arthritis cohort.

OBJECTIVE: To analyze the gut microbiota of patients with rheumatoid arthritis (RA) according to disease activity. METHODS: An observational cross-sectional study of 110 patients with RA and 110 age- and sex-matched controls was performed. Patients were classified according to the disease activity (DAS28 ≥3.2 or DAS28 <3.2). Clinical and epidemiological variables were included. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics analysis based on QIIME and PICRUSt. A multivariate analysis was performed to identify factors associated with inflammatory activity. RESULTS: The mean DAS28 indicated remission/low inflammatory activity in 71 patients (64.5 %) and moderate/high activity in 39 (35.5 %) during follow-up. Alpha and beta diversity analysis revealed differences in gut microbiota between the 3 study groups. In the moderate/high activity RA, we observed a significant change in the abundance of genera compared with the other groups. The abundance of Collinsella and Bifidobacterium was increased in RA patients compared with controls. The metabolic profile of gut microbiota was characterized by differences in pathways related to Biosynthesis, Generation of Precursor Metabolites/Energy, and Degradation/Utilization/Assimilation between the 3 groups. The factors associated with cumulative inflammatory activity in RA were age (OR [95 % CI], 1.065 [1.002-1.131]), obesity (OR [95% CI], 3.829 [1.064-8.785]), HAQ score (OR [95% CI], 2.729 [1.240-5.009]), and expansion of the genus Collinsella (OR [95% CI], 3.000 [1.754-9.940]). CONCLUSIONS: The composition of gut microbiota differed between patients with RA and moderate/high activity, patients with remission/low activity, and controls. The genus Collinsella, age, obesity, and physical function were associated with cumulative inflammatory burden in RA.

Longitudinal Study of Cognitive Functioning in Adults with Juvenile Idiopathic Arthritis.

OBJECTIVE: To prospectively evaluate possible decline of cognitive functions in adult patients with juvenile idiopathic arthritis (JIA) and identify associated factors. PATIENTS AND METHODS: We performed a 24-month prospective observational study of adults (≥16 years) with JIA. The primary outcome measure was decline in cognitive function defined as a worsening of ≥2 points on the scales of the subsets administered to evaluate the different cognitive areas using the Wechsler Adult Intelligence Scale (WAIS) after 24 months: attention/concentration (digit span); verbal function (vocabulary); visual-spatial organization (block design); working memory (letter-number sequencing); and problem solving (similarities). Other variables included average inflammatory activity using C-reactive protein and composite activity indexes, comorbidity, and treatment. Logistic regression was performed to identify factors associated with cognitive decline. RESULTS: The study population comprised 52 patients with JIA. Of these, 15 (28.8%) had cognitive decline at V24. The most affected functions were working memory (17.3%), attention/concentration (9.6%), verbal function (7.7%), visual-spatial organization (7.7%), and problem solving (3.8%). There were no significant differences in the median direct or scale scores for the cognitive functions evaluated between V0 and V24 for the whole sample. The factors associated with cognitive decline in patients with JIA were average C-reactive protein (OR [95% CI], 1.377 [1.060-1.921]; p = 0.039), depression (OR [95% CI], 3.691 [1.294-10.534]; p = 0.015), and treatment with biologics (OR [95% CI], 0.188 [0.039-0.998]; p = 0.046). CONCLUSION: Cognitive decline was detected in almost one third of adults with JIA after 24 months of follow-up. Systemic inflammatory activity in JIA patients was related to cognitive decline. Patients treated with biologics had a lower risk of decline in cognitive functions.

Importance of Vaccination against SARS-CoV-2 in Patients with Interstitial Lung Disease Associated with Systemic Autoimmune Disease.

Objectives: To describe the frequency of COVID-19 and the effect of vaccination in patients with interstitial lung disease and systemic autoimmune disease (ILD-SAD) and to identify factors associated with infection and severity of COVID-19. Methods: We performed a cross-sectional multicenter study of patients with ILD-SAD followed between June and October 2021. The main variable was COVID-19 infection confirmed by a positive polymerase chain reaction (PCR) result for SARS-CoV-2. The secondary variables included severity of COVID-19, if the patient had to be admitted to hospital or died of the disease, and vaccination status. Other variables included clinical and treatment characteristics, pulmonary function and high-resolution computed tomography. Two logistic regression was performed to explore factors associated with "COVID-19" and "severe COVID-19". Results: We included 176 patients with ILD-SAD: 105 (59.7%) had rheumatoid arthritis, 49 (27.8%) systemic sclerosis, and 22 (12.54%) inflammatory myopathies. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/22 (13.22%) died. As to the vaccination, 163/176 (92.6%) patients received the complete doses. The factors associated with SARS-CoV-2 infection were FVC (OR (95% CI), 0.971 (0.946−0.989); p = 0.040), vaccination (OR (95% CI), 0.169 (0.030−0.570); p = 0.004), and rituximab (OR (95% CI), 3.490 (1.129−6.100); p = 0.029). The factors associated with severe COVID-19 were the protective effect of the vaccine (OR (95% CI), 0.024 (0.004−0.170); p < 0.001) and diabetes mellitus (OR (95% CI), 4.923 (1.508−19.097); p = 0.018). Conclusions: Around 13% of patients with ILD-SAD had SARS-CoV-2 infection, which was severe in approximately one-third. Most patients with severe infection were not fully vaccinated.

Postprandial Hyperlipidemia: Association with Inflammation and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis.

OBJECTIVE: To describe postprandial lipidemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis and inflammatory activity. METHODS: Observational study of 80 cases of RA and 80 sex- and age-matched controls. We excluded individuals with dyslipidemia. Postprandial hyperlipidemia (PPHL) was defined as postprandial triglycerides >220 mg/dL and/or postprandial ApoB48 levels >75th percentile (>p75). Plasma lipids, cholesterol, triglycerides, ApoB48, and total ApoB were evaluated at baseline and after a meal. Other variables analyzed included subclinical atherosclerosis (defined as presence of carotid atheromatous plaque), inflammatory activity (disease activity score (DAS28-ESR)), cytokines, apolipoproteins, and physical activity. A multivariate analysis was performed to identify factors associated with PPHL in patients with RA. RESULTS: A total of 75 patients with RA and 67 healthy controls fulfilled the inclusion criteria. PPHL was more frequent in patients with RA than controls (No. (%), 29 (38.70) vs. 15 (22.40); p = 0.036), as was subclinical atherosclerosis (No. (%), 22 (30.10) vs. 10 (14.90); p = 0.032). PPHL in patients with RA was associated with subclinical atherosclerosis (OR (95% CI) 4.69 (1.09-12.11); p = 0.037), TNF-α (OR (95% CI) 2.00 (1.00-3.98); p = 0.048), high-sensitivity C-reactive protein (OR (95% CI) 1.10 (1.01-1.19); p = 0.027), and baseline triglycerides (OR (95% CI) 1.02 (1.00-1.04); p = 0.049). CONCLUSION: PPHL was more frequent in patients with RA than in controls. PPHL in patients with RA was associated with inflammation and subclinical atherosclerosis.