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Rheumatoid arthritis (RA) is an autoimmune disorder with multifactorial etiology; both genetic and environmental factors are known to be involved in pathogenesis. Treatment with disease-modifying antirheumatic drugs (DMARDs) plays an essential role in controlling disease progression and symptoms. DMARDs have immunomodulatory properties and suppress...
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Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the mi...
Recent evidence has demonstrated that Crohn’s disease may have its roots in dysbiosis of the microbiome and other environmental factors. One of the strongest risk factors linked to immune activation appears to be diet. Exclusion diets have been shown to ameliorate inflammation and induce remission in 70–80% of treatment-naïve children at disease on...
Aim
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Me...
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Citations
... Understanding the metabolic signaling between microbes and host is essential for unraveling the mechanistic basis of their interaction. 86,87 The question we need to ask is "can we balance our microbiome from within?" It is known that treatment with drugs can modulate gut microbiota. ...
... Many scientists have theorized probiotic effects of Lactobacillus and tested its use for treating RA. 86,87 An intervention with the combination of L. rhamnosus GR-1and L. reuteri RC-14 in a F I G U R E 2 Modulation of gut microbiota for suppressing inflammation. Microbial surfaces share microbiota and dysbiosis at any mucosal surface leads to immune dysregulation. ...
... A growing body of evidence suggests a role of mucosal surfaces, especially dysbiosis of the gut microbiome in pathogenesis of RA.24,41,81,84,85 Recent advances in biotechnology has of fecal samples has discovered an expansion of certain taxa in RA patients,86,87 which could be due to microbiota's inability to regulate itself. There is a high likelihood that the perturbation induces dysbiosis resulting in a functional and metabolic profile shift which could directly contribute to chronic inflammation in RA. ...
Rheumatoid arthritis (RA) is considered a multifactorial condition where interaction between the genetic and environmental factors lead to immune dysregulation causing autoreactivity. While among the various genetic factors, HLA‐DR4 and DQ8, have been reported to be the strongest risk factors, the role of various environmental factors has been unclear. Though events initiating autoreactivity remain unknown, a mucosal origin of RA has gained attention based on the recent observations with the gut dysbiosis in patients. However, causality of gut dysbiosis has been difficult to prove in humans. Mouse models, especially mice expressing RA‐susceptible and ‐resistant HLA class II genes have helped unravel the complex interactions between genetic factors and gut microbiome. This review describes the interactions between HLA genes and gut dysbiosis in sex‐biased preclinical autoreactivity and discusses the potential use of endogenous commensals as indicators of treatment efficacy as well as therapeutic tool to suppress pro‐inflammatory response in rheumatoid arthritis.
... These include the immune system, glucose homeostasis, lipid metabolism, energy balance, nonalcoholic fatty liver disease, obesity, associated comorbidities, and other metabolic disorders. This is particularly relevant for autoinflammatory diseases like asthma, arthritis, colitis, diabetes, and lupus (Lo et al., 1991;Bach, 2002;Bodkhe et al., 2019;Marietta et al., 2019). Consequently, strategies focusing on the regulation of gut microbiota could offer new perspectives and approaches for treating autoimmune diseases. ...
Background
Recent studies have emphasized the role of gut microbiota in the onset and progression of osteomyelitis. However, the exact types of gut microbiota and their mechanisms of action remain unclear. Additionally, there is a lack of theoretical support for treatments that improve osteomyelitis by altering the gut microbiota.
Methods
In our study, we utilized the largest genome-wide association study (GWAS) meta-analysis to date from the MiBioGen consortium, involving 13,400 participants. The GWAS data for osteomyelitis were sourced from the UK Biobank, which included 4,836 osteomyelitis cases and 486,484 controls. We employed a two-sample Mendelian randomization framework for a detailed investigation into the causal relationship between gut microbiota and osteomyelitis. Our methods included inverse variance weighting, MR-Egger, weighted median, and weighted mode approaches. Additionally, we applied Cochran’s Q statistic to assess the heterogeneity of the instrumental variable.
Results
At the class level, Bacilli and Bacteroidia were positively correlated with the risk of osteomyelitis. At the order level, only Bacteroidales showed a positive association with osteomyelitis. At the genus level, an increased abundance of Butyricimonas, Coprococcus3, and Tyzzerella3 was positively associated with the risk of osteomyelitis, whereas Lachnospira was negatively associated. Sensitivity analyses showed no evidence of heterogeneity or pleiotropy.
Conclusion
This study reveals that classes Bacilli and Bacteroidia, order Bacteroidales, and genera Butyricimonas, Coprococcus3, and Tyzzerella3 are implicated in increasing the risk of osteomyelitis, while the genus Lachnospira is associated with a reduced risk. Future investigations are warranted to elucidate the precise mechanisms through which these specific bacterial groups influence the pathophysiology of osteomyelitis
... Research literature focuses on the direct immunological repercussions of dysbiosis, which has already revealed some new therapy prospects, such as those of maintaining and restoring a functioning gut barrier or of inhibiting the migration of gut-primed immune cells out of the intestines [93]. These therapy options also provide an opportunity to intervene early in the disease cycle, potentially reducing RA symptoms and the need for lifetime pharmaceutical medications. ...
... These therapy options also provide an opportunity to intervene early in the disease cycle, potentially reducing RA symptoms and the need for lifetime pharmaceutical medications. Thus, the notion that existing successful RA medications might also affect the intestinal bacterial flora increases the prospect that gut microbiota modification could be exploited for therapeutic reasons for RA patients [93]. ...
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.
... Several mechanisms by which gut microbiota are associated with arthritis have been proposed. These include regulating the host's immune system (triggering T-cell differentiation), activating APCs through an effect on TLRs or NOD-like receptors (NLRs), aiding in the enzymatic citrullination of peptides, molecular mimicry of antigens, and increasing the intestinal mucosal permeability [62][63][64][65][66][67]. These pathways coalesce to cause an imbalance in the Th17/Treg cell ratio, and this local immune response results in systemic autoimmunity. ...
... The sequence of events occurring in RA confirms the increase in Gram-positive bacteria and depletion of Gram-negative bacteria [64]. The dysbiosis of the gut microbiome leads to the downregulation of TLRs while simultaneously activating pattern recognition receptors (PRRs), which sets into motion a systemic inflammatory response [57,60]. ...
... Probiotics play a pivotal role in reducing the inflammatory manifestations in RA by significantly reducing inflammatory indicators such as C-reactive protein (CRP) [67]. The gut seems to have an increased permeability towards probiotics, which reduces intestinal inflammation [64]. Currently, probiotic supplementation with L. casei is at the forefront of probiotics used in therapy for RA [64,67]. ...
Allergy and immunological disorders like autoimmune diseases are vastly prevalent worldwide. These conditions account for a substantial amount of personal and social burden. Such illnesses have lengthy, uncertain, and spotted courses with unpredictable exacerbations. A definite tendency for improving the overall quality of life of individuals suffering from such diseases is crucial to tackling these diseases, especially through diet or lifestyle modification. Further, interventions like microbiome-based therapeutics such as prebiotics or probiotics were explored. Changes in the microbial population were evident during the flare-up of autoimmune and allergic conditions. The realization that the human microbiome is a central player in immunological diseases is a hallmark of its potential usefulness in therapy for such illnesses. This review focuses on the intricate symphony in the orchestra of the human microbiome and the immune system. New therapeutic strategies involving probiotics appear to be the future of personalized medicine. Through this review, we explore the narrative of probiotics and reaffirm their use as therapeutic and preventive agents in immunological disorders.
... Up to 100 trillion symbiotic microbes live in the gut, and these microbes are involved in the digestion, metabolism, nutrition, disease control, and maintenance of general well-being (26,27). The imbalance of gastrointestinal homeostasis, especially dysbiosis in gut microbiota composition and diversity, results in inflammatory responses and further triggers the occurrence of diseases such as RA (28,29). Probiotics are a potential adjuvant to restore their original intestinal balance and behavior, and to modulate both innate and adaptive immunity in the host. ...
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by swollen joints, discomfort, stiffness, osteoporosis, and reduced functionality. Genetics, smoking, dust inhalation, high BMI, and hormonal and gut microbiota dysbiosis are all likely causes of the onset or development of RA, but the underlying mechanism remains unknown. Compared to healthy controls, patients with RA have a significantly different composition of gut microbiota. It is well known that the human gut microbiota plays a key role in the initiation, maintenance, and operation of the host immune system. Gut microbiota dysbiosis has local or systematic adverse effects on the host immune system, resulting in host susceptibility to various diseases, including RA. Studies on the intestinal microbiota modulation and immunomodulatory properties of probiotics have been reported, in order to identify their potential possibility in prevention and disease activity control of RA. This review summarized current studies on the role and potential mechanisms of gut microbiota in the development and progression of RA, as well as the preventative and therapeutic effects and potential mechanisms of probiotics on RA. Additionally, we proposed the challenges and difficulties in the application of probiotics in RA, providing the direction for the research and application of probiotics in the prevention of RA.
... The folic acid antagonist methotrexate (MTX) is currently the anchor drug for RA treatment-either as a single agent or in combination with other disease-modifying antirheumatic drugs (DMARDs) [20]. Oral MTX can be partially metabolized by the gut microbiota; in turn, the microbiome may be useful in predicting the response to MTX and may also be a potential target in the attempt to improve the response to this drug [21]. Studies in mice have revealed that MTX affects the abundance of some species in the gut and protects against the periodontal bone loss associated with arthritis and periodontal infection [22,23]. ...
This study evaluated the changes in the composition of oral–gut microbiota in patients with rheumatoid arthritis (RA) caused by methotrexate (MTX) and non-surgical periodontal treatment (NSPT). Assessments were performed at baseline (T0), 6 months after MTX treatment (T1), and 45 days after NSPT (T2). The composition of the oral and gut microbiota was assessed by amplifying the V4 region of the 16S gene from subgingival plaques and stools. The results of the analysis of continuous variables were presented descriptively and non-parametric tests and Spearman’s correlation were adopted. A total of 37 patients (27 with periodontitis) were evaluated at T0; 32 patients (24 with periodontitis) at T1; and 28 patients (17 with periodontitis) at T2. MTX tended to reduce the alpha diversity of the oral–gut microbiota, while NSPT appeared to increase the number of different species of oral microbiota. MTX and NSPT influenced beta diversity in the oral microbiota. The relative abundance of oral microbiota was directly influenced by periodontal status. MTX did not affect the periodontal condition but modified the correlations that varied from weak to moderate (p < 0.05) between clinical parameters and the microbiota. MTX and NSPT directly affected the composition and richness of the oral–gut microbiota. However, MTX did not influence periodontal parameters.
... Recent research highlights the potential of therapeutic strategies to target the microbiome in rheumatic diseases by focusing on restoring microbial diversity, abundance, and composition [25]. This approach recognizes the intricate relationship between the gut microbiome and rheumatic diseases. ...
... Exploring potential therapeutic strategies to target the impact of the gut microbiome on gut barrier function and the modulation of the immune system emerges as a comprehensive approach to managing rheumatic diseases [25]. This recognizes the broader influence of the microbiome, extending beyond specific microbial taxa, to impact the overall gut environment, immune responses, and the production of metabolites. ...
Rheumatic diseases are a group of disorders that affect the joints, muscles, and bones. These diseases, such as rheumatoid arthritis, lupus, and psoriatic arthritis, can cause pain, stiffness, and swelling, leading to reduced mobility and disability. Recent studies have identified the microbiome, the diverse community of microorganisms that live in and on the human body, as a potential factor in the development and progression of rheumatic diseases. Harnessing the microbiome offers a promising new avenue for developing therapeutic strategies for these debilitating conditions. There is growing interest in the role of oral and gut microbiomes in the management of rheumatoid arthritis and other autoimmune disease. Microbial metabolites have immunomodulatory properties that could be exploited for rheumatic disorders. A wide range of microorganisms are present in the oral cavity and are found to be vulnerable to the effects of the environment. The physiology and ecology of the microbiota become intimately connected with those of the host, and they critically influence the promotion of health or progression toward disease. This article aims to provide a comprehensive overview of the current state of knowledge on oral and gut microbiome and its potential future role in the management of rheumatic diseases. This article will also discuss newer treatment strategies such as bioinformatic analyses and fecal transplantation.
... The folic acid antagonist methotrexate (MTX) is currently the anchor drug for RA treatmenteither as a single agent or in combination with other disease-modifying antirheumatic drugs (DMARD) [20]. Oral MTX can be partially metabolized by the gut microbiota; in turn, the microbiome may be useful to predict the response to MTX and may also be a potential target in the attempt to improve the response to this drug [21]. Studies in mice have revealed that MTX affects the abundance of some species in the gut and protects against the periodontal bone loss associated with arthritis and periodontal infection [22,23]. ...
This study evaluated the influence of methotrexate (MTX) and non-surgical periodontal treatment (NSPT) on the composition of the oral-gut microbiota in patients with rheumatoid arthritis (RA). Assessments were performed at baseline (T0), 6 months after MTX treatment (T1), and 45 days after NSPT (T2). The composition of the oral and gut microbiota was assessed by amplifying the V4 region of the 16S gene from subgingival plaques and stools. The results of the analysis of continuous variables were presented descriptively and non-parametric tests were adopted. Thirty-seven patients (27 with periodontitis) were evaluated at T0; 32 patients (24 with periodontitis) at T1; and 28 patients (17 with periodontitis) at T2. Nine individuals were lost to follow-up. MTX tended to reduce the alpha diversity of the oral-gut microbiota, while NSPT appeared to increase the number of different species of oral microbiota. MTX and NSPT influenced beta diversity in the oral microbiota. The relative abundance of oral microbiota was directly influenced by periodontal status. MTX did not affect the periodontal condition but modified the interactions between clinical parameters and the oral-gut microbiota. MTX and NSPT directly affected the composition and richness of the oral-gut microbiota. However, MTX did not influence periodontal clinical parameters.
Oliveira, S.R.; De Arruda, J.A.A.; Corrêa, J.D.; Carvalho, V.F.; Medeiros, J.D.; Schneider, A.H.; Machado, C.C.; Duffles, L.F.; Fernandes, G.D.R.; Calderaro, D.C.; Taba Junior, M.; Abreu, L.G.; Fukada, S.Y.; Oliveira, R.D.R.; Louzada-Júnior, P.; Cunha, F.Q.; Silva, T.A. Methotrexate and Non-surgical Periodontal Treatment Change the Oral-Gut Microbiota in Rheumatoid Arthritis: A Longitudinal Study.
... The gut microbiota contributes to the preservation of immunological homeostasis and serves as a gauge of the host's health. This relationship can be disturbed, which can have an impact on mucosal and systemic immunity as well as promote several inflammatory and autoimmune illnesses [4]. ...
... The development of more effective treatment options, such as biologics and conventional disease-modifying anti-rheumatic drugs (DMARDs), has significantly improved the prognosis of rheumatoid arthritis in recent decades, despite the disease's high morbidity and mortality rate [4]. This review aims to summarize the current knowledge about gut microbiome, its role, and its application in the pathogenesis of rheumatoid arthritis. ...
... human After treatment, decrease in Bacteroides fragilis; reduced Enterobacteriaceae [4]. ...
Rheumatoid arthritis is an autoimmune condition that damages and inflames the joints. It causes severe disability and lowers the quality of life. While the precise cause of rheumatoid arthritis is still unknown, mounting evidence suggests that the gut microbiota, a diverse colony of bacteria that inhabits the gastrointestinal tract, may play a vital role in the progression and management of this debilitating condition. By evaluating relationships, probable processes, and therapeutic ramifications, this narrative review intends to examine the complex relationship between intestinal microbiota and rheumatoid arthritis. Additionally, for the management of rheumatoid arthritis, the review will assess prospective therapeutic approaches that target the gut flora. Multiple studies have shown that people with rheumatoid arthritis have dysbiosis or an imbalance in their gut microbial ecosystems. Increased intestinal permeability has been linked to changes in the gut microbiota, which allows the transfer of bacterial products into the bloodstream. A search was undertaken through PubMed in June 2023 using keywords like "microbiota", "rheumatoid arthritis" and "treatment". Overall 42 articles were included. Probiotics, prebiotics, and dietary changes are some examples of therapies that can be used to modify the gut microbiota and lessen symptoms, slower the progression of the disease, and enhance therapy results. Understanding the interplay between intestinal microbiota and rheumatoid arthritis will pave the way for innovative and personalized therapeutic interventions that could revolutionize the management of this chronic autoimmune disease.
... Researchers are also investigating the potential therapeutic applications of manipulating the gut microbiome in treating or managing autoimmune diseases like RA. Some studies have explored the use of probiotics, prebiotics, or fecal microbiota transplantation (FMT) as potential interventions [39]. Collectively, these interventions target the three proposed mechanisms by which the microbiome contributes to RA pathogenesis, including inflammatory responses (Prevotella copri and Lactobacillus), molecular mimicry (Prevotella copri), and loss of intestinal barrier integrity (Collinsella) [20]. ...
... Notably, the gut microbiome emerges as a sentinel, not merely for immune balance but also as an indicator of the host's overall health. A disruption in the equilibrium between host and microbiome can reverberate across mucosal and systemic immunity, potentially giving rise to an array of inflammatory and autoimmune diseases [39]. ...
... As an integral component of an ecological ensemble, the gut microbiome exercises control over immune harmony while also unveiling insights into the host's health. Disruptions in this interaction could trigger a cascade of events with implications for both mucosal and systemic immunity, opening doors to the development of inflammatory and autoimmune disorders [25,39,55]. ...
The aim is better to understand and critically explore and present the available data from observational studies on the pathogenetic role of the microbiome in the development of rheumatoid arthritis (RA). The electronic databases PubMed, Scopus, and Web of Science were screened for the relevant literature published in the last ten years. The primary outcomes investigated included the influence of the gut microbiome on the pathogenesis and development of rheumatoid arthritis, exploring the changes in microbiota diversity and relative abundance of microbial taxa in individuals with RA and healthy controls (HCs). The risk of bias in the included literature was assessed using the GRADE criteria. Ten observational studies were identified and included in the qualitative assessment. A total of 647 individuals with RA were represented in the literature, in addition to 16 individuals with psoriatic arthritis (PsA) and 247 HCs. The biospecimens comprised fecal samples across all the included literature, with 16S rDNA sequencing representing the primary method of biological analyses. Significant differences were observed in the RA microbiome compared to that of HCs: a decrease in Faecalibacterium, Fusicatenibacter, Enterococcus, and Megamonas and increases in Eggerthellales, Collinsella, Prevotella copri, Klebsiella, Escherichia, Eisenbergiella, and Flavobacterium. There are significant alterations in the microbiome of individuals with RA compared to HCs. This includes an increase in Prevotella copri and Lactobacillus and reductions in Collinsella. Collectively, these alterations are proposed to induce inflammatory responses and degrade the integrity of the intestinal barrier; however, further studies are needed to confirm this relationship.
