scholarly journals Probiotic Supplementation for Rheumatoid Arthritis: A Promising Adjuvant Therapy in the Gut Microbiome Era

2021 ◽  
Vol 12 ◽  
Author(s):  
Margarida Ferro ◽  
Sofia Charneca ◽  
Eduardo Dourado ◽  
Catarina Sousa Guerreiro ◽  
João Eurico Fonseca

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuvant therapy for RA. Benefits of probiotic supplementation were reported in animal models of arthritis and human studies, but the current evidence regarding the effect of probiotic supplementation in the management of RA remains insufficient to make definite recommendations. Several different strains of Lactobacillus and Bifidobacteria, as single species or in mixed culture, have been investigated, and some have demonstrated beneficial effects on disease activity in RA human subjects. As of now, L.casei probiotic bacteria seems to be the strongest candidate for application as adjuvant therapy for RA patients. In this review, we highlight the role of GM in the development and progression of RA and summarize the current knowledge on the use of probiotics as a potential adjuvant therapy for RA. We also review the proposed mechanisms whereby probiotics regulate inflammation. Finally, the role of fermented foods is discussed as a possible alternative to probiotic supplements since they have also been reported to have health benefits.

Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Eugenie Macfarlane ◽  
Markus J. Seibel ◽  
Hong Zhou

Abstract Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.


2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.

2005 ◽  
Vol 11 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Ingmar Meinecke ◽  
Edita Rutkauskaite ◽  
Steffen Gay ◽  
Thomas Pap

2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4968
Author(s):  
Samuel García-Arellano ◽  
Luis Alexis Hernández-Palma ◽  
Sergio Cerpa-Cruz ◽  
Gabriela Athziri Sánchez-Zuno ◽  
Melva Guadalupe Herrera-Godina ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.


2018 ◽  
Vol 77 (9) ◽  
pp. 1345-1353 ◽  
Author(s):  
Azita Sohrabian ◽  
Linda Mathsson-Alm ◽  
Monika Hansson ◽  
Ann Knight ◽  
Jörgen Lysholm ◽  
...  

IntroductionIndividual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.MethodsWe have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.ResultsThe majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.ConclusionsOur data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.


Arthritis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Misato Hashizume ◽  
Masahiko Mihara

Several clinical studies have demonstrated that the humanized anti-interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) improves clinical symptoms and prevents progression of joint destruction in rheumatoid arthritis (RA). However, the precise mechanism by which IL-6 blockade leads to the improvement of RA is not well understood. IL-6 promotes synovitis by inducing neovascularization, infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration by producing matrix metalloproteinases (MMPs) in synovial cells and chondrocytes. Moreover, IL-6 is involved in autoimmunity by altering the balance between Th17 cells and Treg. IL-6 also acts on changing lipid concentrations in blood and on inducing the production of hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major player in the pathogenesis of RA, and current evidence indicates that the blockade of IL-6 is a beneficial therapy for RA patients.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3155 ◽  
Author(s):  
Mrinalini Dey ◽  
Maurizio Cutolo ◽  
Elena Nikiphorou

Background: The role of nutrition in the pathogenesis of rheumatic diseases, including rheumatoid arthritis (RA), has gained increasing attention in recent years. A growing number of studies have focussed on the diverse nutritional contents of beverages, and their possible role in the development and progression of RA. Main body: We aimed to summarise the current knowledge on the role of a range of beverages in the context of RA. Beverages have a key role within the mosaic of autoimmunity in RA and potential to alter the microbiome, leading to downstream effects on inflammatory pathways. The molecular contents of beverages, including coffee, tea, and wine, have similarly been found to interfere with immune signalling pathways, some beneficial for disease progression and others less so. Finally, we consider beverages in the context of wider dietary patterns, and how this growing body of evidence may be harnessed by the multidisciplinary team in patient management. Conclusions: While there is increasing work focussing on the role of beverages in RA, integration of discussions around diet and lifestyle in our management of patients remains sparse. Nutrition in RA remains a controversial topic, but future studies, especially on the role of beverages, are likely to shed further light on this in coming years.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Samuel García ◽  
Carmen Conde

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.


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