Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation which are reversed by inflammation control.

OBJECTIVE: to assess how rheumatoid arthritis (RA) and Disease Modifying Anti Rheumatic Drugs (DMARDs) affect gut permeability. METHODS: to explore colonic mucosa integrity, tight junction proteins ZO-1, occludin and claudin 2 were quantified by immunohistochemistry on colonic biopsies in 20 RA patients and 20 age- and sex-matched controls. Staining intensity was assessed by two blinded independent readers. To explore intestinal permeability, serum concentrations of LPS-binding protein (LBP), sCD14 and zonulin-related proteins (ZRP) were evaluated by ELISA in another cohort of 59 RA: 21 patients naive of DMARDs (17 before and after introduction of a conventional synthetic (cs) DMARDs), 38 patients with severe RA (before and after introduction of a biological (b) DMARDs), and 33 healthy controls. RESULTS: Z0-1 protein was less expressed in colon of RA patients than controls (mean score ± SEM of 1.6 ± 0.56 vs 2.0 ± 0.43; p= 0.01), while no significant difference was detected for occludin and claudin-2. RA patients had higher serum LBP and sCD14 concentrations than controls. LBP and sCD14 levels were significantly correlated with DAS28 (r = 0.61, p= 0.005 and r = 0.57, p= 0.01, respectively) while ZRP did not. bDMARD responders had significantly reduced LBP and sCD14 concentrations unlike bDMARDs non-responders and patients treated with csDMARDs. CONCLUSION: RA patients have altered colonic tight junction proteins and increased serum biomarkers of intestinal permeability. There was a correlation between serological markers of intestinal permeability and disease activity as well as bDMARD response. These results suggest a link between impaired gut integrity and systemic inflammation in RA.

Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation which are reversed by inflammation control.

OBJECTIVE: to assess how rheumatoid arthritis (RA) and Disease Modifying Anti Rheumatic Drugs (DMARDs) affect gut permeability. METHODS: to explore colonic mucosa integrity, tight junction proteins ZO-1, occludin and claudin 2 were quantified by immunohistochemistry on colonic biopsies in 20 RA patients and 20 age- and sex-matched controls. Staining intensity was assessed by two blinded independent readers. To explore intestinal permeability, serum concentrations of LPS-binding protein (LBP), sCD14 and zonulin-related proteins (ZRP) were evaluated by ELISA in another cohort of 59 RA: 21 patients naive of DMARDs (17 before and after introduction of a conventional synthetic (cs) DMARDs), 38 patients with severe RA (before and after introduction of a biological (b) DMARDs), and 33 healthy controls. RESULTS: Z0-1 protein was less expressed in colon of RA patients than controls (mean score ± SEM of 1.6 ± 0.56 vs 2.0 ± 0.43; p= 0.01), while no significant difference was detected for occludin and claudin-2. RA patients had higher serum LBP and sCD14 concentrations than controls. LBP and sCD14 levels were significantly correlated with DAS28 (r = 0.61, p= 0.005 and r = 0.57, p= 0.01, respectively) while ZRP did not. bDMARD responders had significantly reduced LBP and sCD14 concentrations unlike bDMARDs non-responders and patients treated with csDMARDs. CONCLUSION: RA patients have altered colonic tight junction proteins and increased serum biomarkers of intestinal permeability. There was a correlation between serological markers of intestinal permeability and disease activity as well as bDMARD response. These results suggest a link between impaired gut integrity and systemic inflammation in RA.

Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease activity in inflammatory rheumatic diseases: a systematic literature review and meta-analysis.

BACKGROUND: Polyunsaturated fatty acid (PUFA) supplementation has been reported to improve disease activity in inflammatory rheumatic diseases (IRDs). However, data are often conflicting and studies insufficiently large to draw conclusions. This systematic literature review and meta-analysis aimed to better estimate the effect of oral supplementation with omega (n)-3 and n-6 PUFA on IRD activity in terms of duration, dose, type, and source. METHODS: The literature was searched in PubMed, EMBASE, and Cochrane Library databases up to October 2020. Studies were reviewed in accordance with PRISMA guidelines. The effect of PUFA supplementation on disease activity was expressed as the standardized mean difference (95% CI). Metaregression and subgroup analyses involved type of IRD, Jadad score, PUFA source (animal or vegetable), and doses. RESULTS: We obtained 42 references; 30 randomized controlled studies were included comparing the effects of PUFA versus control on disease activity (710 IRD patients receiving PUFA supplementation and 710 controls, most with rheumatoid arthritis). We found a significant improvement in pain, swollen and tender joint count, Disease Activity Score in 28 joints, and Health Assessment Questionnaire score in IRD patients receiving PUFA supplementation as compared with controls, with a significant decrease in erythrocyte sedimentation rate but not C-reactive protein level. Although meta-regression revealed no difference by IRD type or source or dose of PUFA supplementation, subgroup analysis revealed more parameters significantly improved with animal- than vegetable-derived PUFAs and 3- to 6-month supplementation. Most studies examined high-dose supplementation (>2 g/day). CONCLUSION: PUFA consumption, especially omega-3 from animal source >2 g/day, may improve IRD activity and might be an adjuvant therapy in rheumatoid arthritis. TRIAL REGISTRATION: The protocol was registered at PROSPERO ( CRD42021253685 ).

Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). METHODS: A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. RESULTS: The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) -3.04 (95% CI -4.47, -1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD -0.54; 95% CI -1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. CONCLUSIONS: Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies' heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.

Dietary recommendations of the French Society for Rheumatology for patients with chronic inflammatory rheumatic diseases.

This article presents the 1st set of dietary recommendations of the French Society for Rheumatology for patients suffering from chronic inflammatory rheumatic diseases (IRD) made by a working group consisting of 12 rheumatology experts, 3 physician nutrition specialists, 1 internal medicine specialist, 1 registered dietician and 3 representatives from patient associations. This group relied on a systematic literature review and on expert opinions, while taking into consideration not only the joint effects of diet in IRD but also the extra-articular ones. Eight general principles and nine recommendations were established. The general principles emphasize that nutritional advice is not a substitute for pharmacological treatment of IRD and that it is an integral part of the patients' overall care, which could help the patient actively participate in their care. The recommendations propose supporting weight loss in subjects who are overweight or obese, a Mediterranean-type diet and supplementation in polyunsaturated fatty acids, mainly omega-3. Conversely, gluten-free diets (in the absence of celiac disease), vegetarian/vegan diets, fasting and elimination of dairy products should not be proposed. Supplementation with vitamins or trace elements is not indicated for controlling chronic IRD activity, while the use of probiotics or spices is not recommended given the limited or disparate data.

Efficacy of Spice Supplementation in Rheumatoid Arthritis: A Systematic Literature Review.

BACKGROUND: Spices, i.e., curcumin, ginger, saffron, and cinnamon, have a thousand-year history of medicinal use in Asia. Modern medicine has begun to explore their therapeutic properties during the last few decades. We aimed to perform a systematic literature review (SLR) of randomized controlled trials (RCTs) assessing the effect of spice supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis, or psoriatic arthritis). METHODS: An SLR of RCTs, reviews, and meta-analyses was performed, searching for articles in MEDLINE/PubMed. Abstracts from international rheumatology and nutrition congresses (2017-2020) were also scrutinized. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration's tool and the Jadad scale. RESULTS: Altogether, six studies, assessing the use of spice supplementation only in RA patients, were included: one on garlic supplementation, two on curcumin, one on ginger, one on cinnamon, and one on saffron supplementation. Garlic, ginger, cinnamon, or saffron supplementation was associated with a decrease in RA clinical activity. However, several points limit the external validity of these studies. No conclusion on the impact of curcumin supplementation on RA activity could be drawn due to low-quality studies. CONCLUSIONS: Garlic, ginger, cinnamon, and saffron supplementation could have a beneficial effect on RA activity, but the risk of bias of these studies is difficult to assess and data are too limited to recommend them in daily practice.

Efficacy of Oral Vitamin Supplementation in Inflammatory Rheumatic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation. RESULTS: The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares. CONCLUSIONS: Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications.