Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 These new data warrant further exploration of the MD, complemented or not with fermented foods, as a potential adjuvant therapy for RA patients, ideally in well-designed studies with large sample sizes and a multidisciplinary team of researchers. + 1634 word(s) 1634 2020-11-18 10:23:11 |
2 format correct + 9 word(s) 1643 2020-11-23 08:55:13 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Dourado, E.; Ferro, M.; Sousa Guerreiro, C.; Fonseca, J.E. Gut Microbiota and Rheumatoid Arthritis. Encyclopedia. Available online: (accessed on 01 December 2023).
Dourado E, Ferro M, Sousa Guerreiro C, Fonseca JE. Gut Microbiota and Rheumatoid Arthritis. Encyclopedia. Available at: Accessed December 01, 2023.
Dourado, Eduardo, Margarida Ferro, Catarina Sousa Guerreiro, João Eurico Fonseca. "Gut Microbiota and Rheumatoid Arthritis" Encyclopedia, (accessed December 01, 2023).
Dourado, E., Ferro, M., Sousa Guerreiro, C., & Fonseca, J.E.(2020, November 20). Gut Microbiota and Rheumatoid Arthritis. In Encyclopedia.
Dourado, Eduardo, et al. "Gut Microbiota and Rheumatoid Arthritis." Encyclopedia. Web. 20 November, 2020.
Gut Microbiota and Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic immune-driven inflammatory disease characterised by synovial inflammation, leading to progressive cartilage and bone destruction, impacting patients’ functional capacity and quality of life. Patients with RA have significant dierences in gut microbiota composition when compared to controls. Intestinal dysbiosis influences the intestinal barrier strength, integrity and function, and diet is considered the main environmental factor impacting gut microbiota. Over the last few years, researchers have focused on the influence of single components of the diet in the modulation of intestinal microbiota in RA rather than whole dietary patterns. Here, we focus on how the Mediterranean diet (MD), a whole dietary pattern, could possibly act as an adjuvant therapeutic approach, modulating intestinal microbiota and intestinal barrier function in order to improve RA-related outcomes. We also review the potential e ects of particular components of the MD, such as n-3 polyunsaturated fatty acids (PUFAs), polyphenols and fibre.

Rheumatoid arthritis Gut microbiota Mediterranean Diet

1. Gut Microbiota Composition

The human gut houses the largest population of non-eukaryotic organisms in the human body. Despite the high variability between individuals’ gut microbiota composition, bacteria are consistently (and by far) the most common microorganisms [1][2][3]Bacteroidetes and Firmicutes are the most abundant phyla [1][2][4]. Significant inter-individual differences in the prevalence of certain species within these phylae have been reported, resulting from different genetic backgrounds, dietary habits, lifestyle, hygiene practice, drug use and other environmental factors [4][5][6]. The composition of the gut microbiome in people living in distinct geographical areas has a strong association with each population’s dietary habits [2][6].

Urbanisation has been closely related to a Western dietary style, antibiotic use and pollution. It induces changes in gut microbiota composition, particularly the loss of intra-individual microbial diversity accompanied by higher inter-individual differences [7]. In non-Westernised communities, people tend to have a more homogeneous and diverse gut microbiome [7][8][9]. Their gut microbiota tends to be rich in certain bacteria, such as Bacteroidetes (including Prevotella and Xylanibacter), and poor in Firmicutes [6][7][9].

Three different classes of enterotypes have been proposed according to the abundance of BacteroidesPrevotella and Ruminococcus, respectively [2]. There is a strong association between the individual enterotype and long-term but not short-term diet [10].

A healthy microbiota is characterised by the presence of numerous classes of bacteria, with a balanced composition of symbiont and pathobiont organisms [11]. A pathobiont is a permanent resident of the microbiota that does not usually elicit an inflammatory response, but under particular environmentally-induced conditions has the potential to cause dysregulated inflammation and induce disease [11]. A shift in the microbiota composition, with either an increase in pathobionts or a reduction in symbionts, leads to a state of dysbiosis [11] that disturbs the modulation of the host immune function by the gut microbiota [5][11].

2. Gut Microbiota, Mucosal Immune System and Intestinal Permeability

The mucosal immune system and intestinal microbiota can influence each other, promoting a balance between tolerance to dietary antigens and protection against harmful pathogens [4][5][12]. Antigen-presenting cells located at the mucosal surface, once activated by antigens, can regulate immune tolerance by promoting T cell differentiation into regulatory T cells (Tregs) [13]. Tregs suppress inappropriate activation of effector T cells by secreting anti-inflammatory cytokines [4][14]. The gut microbiota influences the number and function of colonic Tregs [15], suggesting that the modulation of gut microbiota may also regulate the mechanism of gut immune tolerance. Most importantly, these interactions may also modulate systemic inflammation, and influence the risk of developing systemic autoimmune diseases [16], including inflammatory arthropathies [16].

The production of short-chain fatty acids (SCFAs) is one of the proposed mechanisms by which intestinal microbiota affects Treg cells differentiation and systemic inflammation [17]. SCFAs, particularly butyrate, acetate and propionate, are the key metabolites resulting from the microbial fermentation of dietary fibres [7][17][18][19]. When fermentable fibres are in short supply, bacteria switch to energetically less favourable sources for growth, such as amino acids or dietary fats [20], resulting in the reduced fermentative activity of the microbiota and SCFA scarcity [17]. SCFAs are an energy source for gut epithelial cells, having an indirect anti-inflammatory effect by improving the assembly of tight junctions and enhancing intestinal barrier function [7][21]. Butyrate is the preferred energy source for colonocytes and is locally consumed, whereas other absorbed SCFAs drain into the systemic circulation [17]. Histone acetylation is thought to increase accessibility to the transcriptional machinery, to promote gene transcription. Butyrate and propionate are known to act as histone deacetylase inhibitors [22]. Through this mechanism, SCFAs may act as systemic anti-inflammatory or immune-suppressive molecules [17]. Despite the low concentration in the periphery, propionate and butyrate affect peripheral organs indirectly by activation of the hormonal and nervous systems [17].

The modulation of intestinal permeability is another mechanism that may explain the influence of gut microbiota on the appearance and perpetuation of inflammatory diseases [23], leading to systemic inflammation. The intestinal lumen is occupied by various exogenous constituents such as microorganisms, toxins and food antigens. The mucosal barrier, which separates the intestinal milieu from the luminal environment, has an essential role in blocking the entry of microorganisms and toxins, while, at the same time, it must allow the absorption of nutrients and water [24][25]. Intestinal barrier strength and function can be affected by several factors, among which diet, gut microbiota composition and mucosal immune system integrity are key factors [26][27][28][29]. When the mucosal barrier is disturbed, the exogenous luminal constituents invade the intestinal milieu, and immune activation and mucosal inflammation ensue [14][23][30]. This process can trigger an abnormal immune response resulting in both local and systemic inflammation, increasing the risk of developing both gut-associated and extra-intestinal diseases [23][26][29][31].

3. Gut Microbiota and Rheumatoid Arthritis Pathogenesis

Over the last few years, emerging evidence has reported the involvement of gut dysbiosis in the onset of autoimmune diseases such as RA [29,30,57], suggesting its role in contributing to a breakdown of immune tolerance [24][26][32][33].

The natural history of RA includes different stages, including an at-risk pre-symptomatic phase and an early arthritis phase before the classical erosive disease phase [4][32][34][35][36]. The most noticeable players in the preclinical RA phases are the autoantibodies, a hallmark of RA [4][34]. RA-associated autoantibodies include rheumatoid factor (RF) [37][38], antibodies to citrullinated proteins (ACPA) [39] and anti-carbamylated peptide antibodies (anti-CarP) [40]. High serum concentrations of RF [41], ACPA [42], and anti-CarP [43] can be detected years before the onset of clinically overt RA. The evolution of the autoantibody profile in the preclinical stage of RA includes isotype switching [4]. The higher prevalence of IgA- than IgG-ACPA in high-RA-risk populations suggests that mucosal immune responses are important in the preclinical phases of the disease [4]. In different groups of individuals who later developed RA, a higher prevalence of serum IgA- and IgM-RF than IgG-RF was found, and IgA-RF appeared earliest [44].

Growing evidence suggests that the dysbiosis of mucosal microbiota is closely related to local autoimmune processes [45], and the composition of the microbiota is significantly disturbed in patients with both early and long-standing RA [46]. It is also known that dysbiosis in the oral microbiota induces periodontitis [47] and that the gingiva of patients with periodontitis contains citrullinated proteins and ACPA [48][49]Porphyromonas gingivalis, a common periodontal pathogen, can citrullinate targets for ACPA [50], suggesting that dysbiosis and periodontitis can play a fundamental role in the early loss of tolerance to self-antigens in RA-susceptible patients [33][51][52].

Different mechanisms can explain the dysbiosis-mediated induction of autoantibodies. The most common theory states that T helper cells can originate from T cell responses to external antigens through molecular mimicry between those antigens and self-antigens [4][53][54]. Such activation leads to the positive selection and maturation of self-reactive B cells that produce a variety of RA-associated autoantibodies [53][55][56]. It has also been proposed that host cell necrosis and apoptosis, occurring as a consequence of bacterial insult, can result in extracellular exposure of intracellular self-antigens, leading to recognition by B cells and autoantibody production [56].

Recently, it has been shown that the gut microbiota of RA patients has a significant increase in the class of Bacilli and the order of Lactobacillales compared to healthy controls [57][58]. This is concordant with data reporting an increase in the Lactobacillaceae family and the Lactobacillus genus in mice susceptible to collagen-induced arthritis [59]. The variety of Lactobacilli is also higher in RA patients [58]. Excess Lactobacillus salivarius in the gut and mouth of RA patients has been described, and a correlation with disease severity has been proposed [60]. Paradoxically, the administration of Lactobacillus acidophilus and Lactobacillus casei (L. casei) seems to be beneficial for RA disease activity, suggesting that different Lactobacilli probably have different roles in RA pathogenesis and disease activity modulation [61][62].

On the other hand, significant reductions of the genus FlavobacteriumFaecalibacterium and other butyrate-producing taxa [57][63][64], as well as its related species Faecalibacterium prausnitzii and the species Blautia coccoides were described [30].

Moreover, a higher prevalence of Euryarchaeota, Gammaproteobacteria, Pasteurellales, and Anaerobranca zavarzinii was correlated with a higher disease activity score-28 (DAS28), whilst Erysipelotrichi, Erysipelotrichales, Coriobacteriales, Coriobacteriaceae, Lactobacillaceae, Collinsella, Bacteroides rodentium, and Collinsella aerofaciens were inversely associated with this score [57].

Importantly, it has also been shown that RA patients under treatment with etanercept, a fusion protein consisting of a human tumour necrosis factor (TNF) receptor linked to the Fc portion of human immunoglobulin G1 (IgG1), present a partial restoration of a beneficial microbiota [57]. This fact seems to provide further evidence pointing towards gut dysbiosis as a hallmark of the disease.

4. Gut Microbiota and Drug Metabolism

Pharmacomicrobiomics is an emerging field that investigates the effect of variations within the human gut microbiome on drugs [65]. The variability between individuals in the composition and metabolic competence of their microbiomes has a unique role in determining the bioavailability, clinical efficacy and toxicity of a wide array of drugs, including DMARDs [65]. This variability arises because specific, direct modifications of the chemical structures of ingested drugs are dependent on the composition of the human gut microbiome and its collective enzymatic activity [66][67].

Relevant examples include the prodrug sulfasalazine, which requires cleaving by the gut microbiome to become an active drug [68], as well as cyclophosphamide and methotrexate [65]. Although our basic understanding of how microbiome-dependent biotransformations of xenobiotics affect human health is still incomplete, numerous studies have highlighted the extent to which microbial xenobiotic metabolism varies between individuals, and how these reactions can be manipulated for therapeutic purposes [65][69][70]. Diet modifications and probiotics are the biggest candidates to play this modulatory role.


  1. Eckburg, P.B. Diversity of the Human Intestinal Microbial Flora. Science 2005, 308, 1635–1638.
  2. Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D.R.; Fernandes, G.R.; Tap, J.; Bruls, T.; Batto, J.-M.; et al. Enterotypes of the human gut microbiome. Nature 2011, 473, 174–180.
  3. Jethwa, H.; Abraham, S. The evidence for microbiome manipulation in inflammatory arthritis. Rheumatology 2016, kew374.
  4. Kalinkovich, A.; Livshits, G. A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies. Semin. Arthritis Rheum. 2019, 49, 474–484.
  5. Van de Wiele, T.; Van Praet, J.T.; Marzorati, M.; Drennan, M.B.; Elewaut, D. How the microbiota shapes rheumatic diseases. Nat. Rev. Rheumatol. 2016, 12, 398–411.
  6. Rothschild, D.; Weissbrod, O.; Barkan, E.; Kurilshikov, A.; Korem, T.; Zeevi, D.; Costea, P.I.; Godneva, A.; Kalka, I.N.; Bar, N.; et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 2018, 555, 210–215.
  7. Kolodziejczyk, A.A.; Zheng, D.; Elinav, E. Diet–microbiota interactions and personalized nutrition. Nat. Rev. Microbiol 2019, 17, 742–753.
  8. Obregon-Tito, A.J.; Tito, R.Y.; Metcalf, J.; Sankaranarayanan, K.; Clemente, J.C.; Ursell, L.K.; Zech Xu, Z.; Van Treuren, W.; Knight, R.; Gaffney, P.M.; et al. Subsistence strategies in traditional societies distinguish gut microbiomes. Nat. Commun. 2015, 6, 6505.
  9. Schnorr, S.L.; Candela, M.; Rampelli, S.; Centanni, M.; Consolandi, C.; Basaglia, G.; Turroni, S.; Biagi, E.; Peano, C.; Severgnini, M.; et al. Gut microbiome of the Hadza hunter-gatherers. Nat. Commun. 2014, 5, 3654.
  10. Wu, G.D.; Chen, J.; Hoffmann, C.; Bittinger, K.; Chen, Y.-Y.; Keilbaugh, S.A.; Bewtra, M.; Knights, D.; Walters, W.A.; Knight, R.; et al. Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes. Science 2011, 334, 105–108.
  11. Round, J.L.; Mazmanian, S.K. The gut microbiome shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 2009, 9, 313–323.
  12. Hooper, L.V.; Macpherson, A.J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 2010, 10, 159–169.
  13. Shi, N.; Li, N.; Duan, X.; Niu, H. Interaction between the gut microbiome and mucosal immune system. Mil. Med. Res. 2017, 4.
  14. Kayama, H.; Okumura, R.; Takeda, K. Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine. Annu. Rev. Immunol. 2020, 38, 23–48.
  15. Tanoue, T.; Atarashi, K.; Honda, K. Development and maintenance of intestinal regulatory T cells. Nat. Rev. Immunol. 2016, 16, 295–309.
  16. Opazo, M.C.; Ortega-Rocha, E.M.; Coronado-Arrázola, I.; Bonifaz, L.C.; Boudin, H.; Neunlist, M.; Bueno, S.M.; Kalergis, A.M.; Riedel, C.A. Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases. Front. Microbiol. 2018, 9.
  17. Koh, A.; De Vadder, F.; Kovatcheva-Datchary, P.; Bäckhed, F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell 2016, 165, 1332–1345.
  18. Holscher, H.D. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes 2017, 8, 172–184.
  19. Cummings, J.H.; Pomare, E.W.; Branch, W.J.; Naylor, C.P.; Macfarlane, G.T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 1987, 28, 1221–1227.
  20. Cummings, J.H.; Macfarlane, G.T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 1991, 70, 443–459.
  21. Peng, L.; Li, Z.-R.; Green, R.S.; Holzman, I.R.; Lin, J. Butyrate Enhances the Intestinal Barrier by Facilitating Tight Junction Assembly via Activation of AMP-Activated Protein Kinase in Caco-2 Cell Monolayers. J. Nutr. 2009, 139, 1619–1625.
  22. Johnstone, R.W. Histone-deacetylase inhibitors: Novel drugs for the treatment of cancer. Nat. Rev. Drug Discov. 2002, 1, 287–299.
  23. Nagpal, R.; Yadav, H. Bacterial Translocation from the Gut to the Distant Organs: An Overview. Ann. Nutr. Metab. 2017, 71, 11–16.
  24. Deane, K.D.; Demoruelle, M.K.; Kelmenson, L.B.; Kuhn, K.A.; Norris, J.M.; Holers, V.M. Genetic and environmental risk factors for rheumatoid arthritis. Best Pr. Res. Clin. Rheumatol. 2017, 31, 3–18.
  25. Van Spaendonk, H.; Ceuleers, H.; Witters, L.; Patteet, E.; Joossens, J.; Augustyns, K.; Lambeir, A.-M.; De Meester, I.; De Man, J.G.; De Winter, B.Y. Regulation of intestinal permeability: The role of proteases. World J. Gastroenterol. 2017, 23, 2106–2123.
  26. Mu, Q.; Kirby, J.; Reilly, C.M.; Luo, X.M. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front. Immunol. 2017, 8.
  27. De Santis, S.; Cavalcanti, E.; Mastronardi, M.; Jirillo, E.; Chieppa, M. Nutritional Keys for Intestinal Barrier Modulation. Front. Immunol. 2015, 6.
  28. Bischoff, S.C.; Barbara, G.; Buurman, W.; Ockhuizen, T.; Schulzke, J.-D.; Serino, M.; Tilg, H.; Watson, A.; Wells, J.M. Intestinal permeability—A new target for disease prevention and therapy. BMC Gastroenterol. 2014, 14.
  29. Lin, L.; Zhang, J. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. BMC Immunol. 2017, 18, 2.
  30. Ahmad, R.; Sorrell, M.; Batra, S.; Dhawan, P.; Singh, A. Gut permeability and mucosal inflammation: Bad, good or context dependent. Mucosal Immunol. 2017, 10, 307–317.
  31. Farré, R.; Fiorani, M.; Abdu Rahiman, S.; Matteoli, G. Intestinal Permeability, Inflammation and the Role of Nutrients. Nutrients 2020, 12, 1185.
  32. Demoruelle, M.K.; Deane, K.D.; Holers, V.M. When and Where Does Inflammation Begin in Rheumatoid Arthritis? Curr. Opin. Rheumatol. 2014, 26, 64–71.
  33. Kalinkovich, A.; Gabdulina, G.; Livshits, G. Autoimmunity, inflammation, and dysbiosis mutually govern the transition from the preclinical to the clinical stage of rheumatoid arthritis. Immunol. Res. 2018, 66, 696–709.
  34. Ma, W.-T.; Chang, C.; Gershwin, M.E.; Lian, Z.-X. Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A comprehensive review. J. Autoimmun. 2017, 83, 95–112.
  35. Falkenburg, W.J.J.; Van Schaardenburg, D. Evolution of autoantibody responses in individuals at risk of rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol. 2017, 31, 42–52.
  36. Tracy, A.; Buckley, C.D.; Raza, K. Pre-symptomatic autoimmunity in rheumatoid arthritis: When does the disease start? Semin. Immunopathol. 2017, 39, 423–435.
  37. Waaler, E. On the occurrence of a factor in human serum activating the specific agglutination of sheep blood corpuscles. Acta Pathol. Microbiol. Scand. 2009, 17, 172–188.
  38. Rose, H.M.; Ragan, C.; Pearce, E.; Lipman, M.O. Differential Agglutination of Normal and Sensitized Sheep Erythrocytes by Sera of Patients with Rheumatoid Arthritis. Exp. Biol. Med. 1948, 68, 1–6.
  39. Schellekens, G.A.; De Jong, B.A.; Van den Hoogen, F.H.; Van de Putte, L.B.; Van Venrooij, W.J. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J. Clin. Investig. 1998, 101, 273–281.
  40. Shi, J.; Knevel, R.; Suwannalai, P.; Van der Linden, M.P.; Janssen, G.M.C.; Van Veelen, P.A.; Levarht, N.E.W.; Van der Helm-van Mil, A.H.M.; Cerami, A.; Huizinga, T.W.J.; et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc. Natl. Acad. Sci. USA 2011, 108, 17372–17377.
  41. Aho, K.; Heliovaara, M.; Knekt, P.; Reunanen, A.; Aromaa, A.; Leino, A.; Kurki, P.; Heikkila, R.; Palosuo, T. Serum immunoglobulins and the risk of rheumatoid arthritis. Ann. Rheum. Dis. 1997, 56, 351–356.
  42. Van de Stadt, L.A.; De Koning, M.H.M.T.; Van de Stadt, R.J.; Wolbink, G.; Dijkmans, B.A.C.; Hamann, D.; Van Schaardenburg, D. Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis. Arthritis Rheum. 2011, 63, 3226–3233.
  43. Brink, M.; Verheul, M.K.; Rönnelid, J.; Berglin, E.; Holmdahl, R.; Toes, R.; Klareskog, L.; Trouw, L.A.; Rantapää-Dahlqvist, S. Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage. Arthritis Res. 2015, 17, 25.
  44. Brink, M.; Hansson, M.; Mathsson-Alm, L.; Wijayatunga, P.; Verheul, M.K.; Trouw, L.A.; Holmdahl, R.; Rönnelid, J.; Klareskog, L.; Rantapää-Dahlqvist, S. Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis. Arthritis Res. 2016, 18, 43.
  45. Pordeus, V.; Szyper-Kravitz, M.; Levy, R.A.; Vaz, N.M.; Shoenfeld, Y. Infections and Autoimmunity: A Panorama. Clin. Rev. Allerg. Immunol. 2008, 34, 283–299.
  46. Maeda, Y.; Takeda, K. Role of Gut Microbiota in Rheumatoid Arthritis. JCM 2017, 6, 60.
  47. Kilian, M.; Chapple, I.L.C.; Hannig, M.; Marsh, P.D.; Meuric, V.; Pedersen, A.M.L.; Tonetti, M.S.; Wade, W.G.; Zaura, E. The oral microbiome—An update for oral healthcare professionals. Br. Dent. J. 2016, 221, 657–666.
  48. Diamanti, A.P.; Manuela Rosado, M.; Laganà, B.; D’Amelio, R. Microbiota and chronic inflammatory arthritis: An interwoven link. J. Transl. Med. 2016, 14, 233.
  49. Nesse, W.; Westra, J.; Wal, J.E.; Abbas, F.; Nicholas, A.P.; Vissink, A.; Brouwer, E. The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation. J. Clin. Periodontol. 2012, 39, 599–607.
  50. Wegner, N.; Wait, R.; Sroka, A.; Eick, S.; Nguyen, K.-A.; Lundberg, K.; Kinloch, A.; Culshaw, S.; Potempa, J.; Venables, P.J. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: Implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010, 62, 2662–2672.
  51. Lerner, A.; Aminov, R.; Matthias, T. Dysbiosis May Trigger Autoimmune Diseases via Inappropriate Post-Translational Modification of Host Proteins. Front. Microbiol. 2016, 7.
  52. Horta-Baas, G.; Romero-Figueroa, M.D.S.; Montiel-Jarquín, A.J.; Pizano-Zárate, M.L.; García-Mena, J.; Durán, N.R. Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis. J. Immunol. Res. 2017, 2017.
  53. Rosenblum, M.D.; Remedios, K.A.; Abbas, A.K. Mechanisms of human autoimmunity. J. Clin. Investig. 2015, 125, 2228–2233.
  54. Marrack, P.; Kappler, J.; Kotzin, B.L. Autoimmune disease: Why and where it occurs. Nat. Med. 2001, 7, 899–905.
  55. Pianta, A.; Arvikar, S.L.; Strle, K.; Drouin, E.E.; Wang, Q.; Costello, C.E.; Steere, A.C. Two rheumatoid arthritis–specific autoantigens correlate microbial immunity with autoimmune responses in joints. J. Clin. Investig. 2017, 127, 2946–2956.
  56. Suurmond, J.; Diamond, B. Autoantibodies in systemic autoimmune diseases: Specificity and pathogenicity. J. Clin. Investig. 2015, 125, 2194–2202.
  57. Picchianti-Diamanti, A.; Panebianco, C.; Salemi, S.; Sorgi, M.; Di Rosa, R.; Tropea, A.; Sgrulletti, M.; Salerno, G.; Terracciano, F.; D’Amelio, R.; et al. Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept. IJMS 2018, 19, 2938.
  58. Liu, X.; Zou, Q.; Zeng, B.; Fang, Y.; Wei, H. Analysis of Fecal Lactobacillus Community Structure in Patients with Early Rheumatoid Arthritis. Curr. Microbiol. 2013, 67, 170–176.
  59. Liu, X.; Zeng, B.; Zhang, J.; Li, W.; Mou, F.; Wang, H.; Zou, Q.; Zhong, B.; Wu, L.; Wei, H.; et al. Role of the Gut Microbiome in Modulating Arthritis Progression in Mice. Sci. Rep. 2016, 6, 30594.
  60. Zhang, X.; Zhang, D.; Jia, H.; Feng, Q.; Wang, D.; Liang, D.; Wu, X.; Li, J.; Tang, L.; Li, Y.; et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 2015, 21, 895–905.
  61. Alipour, B.; Homayouni-Rad, A.; Vaghef-Mehrabany, E.; Sharif, S.K.; Vaghef-Mehrabany, L.; Asghari-Jafarabadi, M.; Nakhjavani, M.R.; Mohtadi-Nia, J. Effects of Lactobacillus casei supplementation on disease activity and inflammatory cytokines in rheumatoid arthritis patients: A randomized double-blind clinical trial. Int. J. Rheum. Dis. 2014.
  62. Vaghef-Mehrabany, E.; Alipour, B.; Homayouni-Rad, A.; Sharif, S.-K.; Asghari-Jafarabadi, M.; Zavvari, S. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition 2014, 30, 430–435.
  63. Chen, J.; Wright, K.; Davis, J.M.; Jeraldo, P.; Marietta, E.V.; Murray, J.; Nelson, H.; Matteson, E.L.; Taneja, V. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 2016, 8, 43.
  64. Wu, X.; Liu, J.; Xiao, L.; Lu, A.; Zhang, G. Alterations of Gut Microbiome in Rheumatoid Arthritis. Osteoarthr. Cartil. 2017, 25, S287–S288.
  65. Scher, J.U.; Nayak, R.R.; Ubeda, C.; Turnbaugh, P.J.; Abramson, S.B. Pharmacomicrobiomics in inflammatory arthritis: Gut microbiome as modulator of therapeutic response. Nat. Rev. Rheumatol. 2020, 16, 282–292.
  66. Sousa, T.; Paterson, R.; Moore, V.; Carlsson, A.; Abrahamsson, B.; Basit, A.W. The gastrointestinal microbiota as a site for the biotransformation of drugs. Int. J. Pharm. 2008, 363, 1–25.
  67. Birer, C.; Wright, E.S. Capturing the Complex Interplay Between Drugs and the Intestinal Microbiome. Clin. Pharmacol. Ther. 2019, 106, 501–504.
  68. Peppercorn, M.A.; Goldman, P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J. Pharmacol. Exp. Ther. 1972, 181, 555–562.
  69. Sharma, A.K.; Jaiswal, S.K.; Chaudhary, N.; Sharma, V.K. A novel approach for the prediction of species-specific biotransformation of xenobiotic/drug molecules by the human gut microbiota. Sci. Rep. 2017, 7, 9751.
  70. Spanogiannopoulos, P.; Bess, E.N.; Carmody, R.N.; Turnbaugh, P.J. The microbial pharmacists within us: A metagenomic view of xenobiotic metabolism. Nat. Rev. Microbiol. 2016, 14, 273–287.
Subjects: Others
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , ,
View Times: 375
Revisions: 2 times (View History)
Update Date: 18 Jan 2022