Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804–10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Malard F, Dore J, Gaugler B, Mohty M. Introduction to host microbiome symbiosis in health and disease. Mucosal Immunol. 2021;14(3):547–54.

Article  CAS  PubMed  Google Scholar 

Wilkins LJ, Monga M, Miller AW. Defining dysbiosis for a cluster of chronic diseases. Sci Rep. 2019;9(1):12918.

Article  PubMed  PubMed Central  Google Scholar 

Clemente JC, Manasson J, Scher JU. The role of the gut microbiome in systemic inflammatory disease. BMJ. 2018;360: j5145.

Article  PubMed  PubMed Central  Google Scholar 

Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife. 2013;2:e01202.

Dagar S, Singh J, Saini A, Kumar Y, Chhabra S, Minz RW, et al. Gut bacteriome, mycobiome and virome alterations in rheumatoid arthritis. Front Endocrinol. 2023;13:1044673.

Wang D-W, Pang X-T, Zhang H, Gao H-X, Leng Y-F, Chen F-Q, et al. Gut microbial dysbiosis in rheumatoid arthritis: A systematic review protocol of case-control studies. BMJ Open. 2022;12(4): e052021.

Article  PubMed  PubMed Central  Google Scholar 

Attur M, Scher JU, Abramson SB, Attur M. Role of intestinal dysbiosis and nutrition in rheumatoid arthritis. Cells. 2022;11(15):2436.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wilson TM, Trent B, Kuhn KA, Demoruelle MK. Microbial influences of mucosal immunity in rheumatoid arthritis. Curr Rheumatol Rep. 2020;22(11):83.

Article  PubMed  PubMed Central  Google Scholar 

Konig MF. The microbiome in autoimmune rheumatic disease. Best Pract Res Clin Rheumatol. 2020;34(1): 101473.

Article  PubMed  PubMed Central  Google Scholar 

Chriswell ME, Kuhn KA. Microbiota-mediated mucosal inflammation in arthritis. Best Pract Res Clin Rheumatol. 2019;33(6): 101492.

Article  PubMed  Google Scholar 

Holers VM, Demoruelle MK, Kuhn KA, Buckner JH, Robinson WH, Okamoto Y, et al. Rheumatoid arthritis and the mucosal origins hypothesis: Protection turns to destruction. Nat Rev Rheumatol. 2018;14(9):542–57.

Article  PubMed  PubMed Central  Google Scholar 

Deane KD. Preclinical Rheumatoid Arthritis and Rheumatoid Arthritis Prevention. Curr Rheumatol Rep. 2018;20(8):50. 

Romero V, Fert-Bober J, Nigrovic PA, Darrah E, Haque UJ, Lee DM, et al. Immune-mediated pore-forming pathways induce cellular hypercitrullination and generate citrullinated autoantigens in rheumatoid arthritis. Sci Transl Med. 2013;5(209):209ra150–1.

Article  PubMed  PubMed Central  Google Scholar 

Gabarrini G, de Smit M, Westra J, Brouwer E, Vissink A, Zhou K, et al. The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis. Sci Rep. 2015;5(1):13936.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wegner N, Wait R, Sroka A, Eick S, Nguyen K-A, Lundberg K, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: Implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010;62(9):2662–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K, et al. Aggregatibacter actinomycetemcomitans–induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med. 2016;8(369):369ra176-369ra1.

Article  PubMed  PubMed Central  Google Scholar 

Möller B, Kollert F, Sculean A, Villiger PM. Infectious triggers in periodontitis and the gut in rheumatoid arthritis (RA): A complex story about association and causality. Front Immunol. 2020;11:1108.

Maeda Y, Takeda K. Host–microbiota interactions in rheumatoid arthritis. Exp Mol Med. 2019;51(12):1–6.

Article  CAS  PubMed  Google Scholar 

Gómez-Bañuelos E, Mukherjee A, Darrah E, Andrade F. Rheumatoid arthritis-associated mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. J Clin Med. 2019;8(9):1309.

Article  PubMed  PubMed Central  Google Scholar 

Clark RA. Fishing with autoantibodies nets a gut bacteria that drives arthritis. Sci Immunol. 2022;7(78):eadf9316.

Article  PubMed  Google Scholar 

•• Chriswell ME, Lefferts AR, Clay MR, Hsu AR, Seifert J, Feser ML, et al. Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Sci Transl Med. 2022;14(668):eabn5166 In this study, the authors utilize monoclonal antibodies derived from individuals at risk for and with RA to identify potentially cross-reactive bacteria and demonstrate that these antibody-bound bacteria are able to induce T cell responses in patients with RA as well as arthritis in mice.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Brewer RC, Lanz TV, Hale CR, Sepich-Poore GD, Martino C, Swafford AD, et al. Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis. Sci Transl Med. 2023;15(684):eabq8476. This study describes the presence of citrullinated oral bacteria in the circulation of patients with RA to which ACPA as well as associated anti-citrullinated bacteria antibodies could bind..

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moentadj R, Wang Y, Bowerman K, Rehaume L, Nel H, Cuiv PO, et al. Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice. Ann Rheum Dis. 2021;80(5):573–81.

Article  CAS  PubMed  Google Scholar 

Lim JJ, Jones CM, Loh TJ, Ting YT, Zareie P, Loh KL, et al. The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR. Sci Immunol. 2021;6(58):eabe0896.

Article  CAS  PubMed  Google Scholar 

Nguyen H, James EA. Immune recognition of citrullinated epitopes. Immunology. 2016;149(2):131–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alpizar-Rodriguez D, Lesker TR, Gronow A, Gilbert B, Raemy E, Lamacchia C, et al. Prevotella copri in individuals at risk for rheumatoid arthritis. Ann Rheum Dis. 2019;78(5):590–3.

Article  CAS  PubMed  Google Scholar 

Abdelsalam NA, Hegazy SM, Aziz RK. The curious case of Prevotella copri. Gut Microbes. 2023;15(2):2249152.

Miyauchi E, Shimokawa C, Steimle A, Desai MS, Ohno H. The impact of the gut microbiome on extra-intestinal autoimmune diseases. Nat Rev Immunol. 2023;23(1):9–23.

Article  CAS  PubMed  Google Scholar 

Pianta A, Arvikar S, Strle K, Drouin EE, Wang Q, Costello CE, et al. Evidence of the immune relevance of Prevotella copri, a gut microbe, in patients with rheumatoid arthritis. Arthritis & Rheumatology. 2017;69(5):964–75.

Article  CAS  Google Scholar 

Pianta A, Arvikar SL, Strle K, Drouin EE, Wang Q, Costello CE, et al. Two rheumatoid arthritis–specific autoantigens correlate microbial immunity with autoimmune responses in joints. J Clin Investig. 2017;127(8):2946–56.

Article  PubMed  PubMed Central  Google Scholar 

• Pianta A, Chiumento G, Ramsden K, Wang Q, Strle K, Arvikar S, et al. Identification of novel, immunogenic HLA–DR-presented Prevotella copri peptides in patients with rheumatoid arthritis. Arthritis Rheumatol. 2021;73(12):2200–5. This study identifies through mass spectrometry P. copri neoepitopes that stimulate T cells from patients with RA.

Wang H, Ong E, Kao JY, Sun D, He Y. Reverse microbiomics: A new reverse dysbiosis analysis strategy and its usage in prediction of autoantigens and virulent factors in dysbiotic gut microbiomes from rheumatoid arthritis patients. Front Microbiol. 2021;12:633732.

•• Nii T, Maeda Y, Motooka D, Naito M, Matsumoto Y, Ogawa T, et al. Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis. Ann Rheum Dis. 2023;82(5):621–9. In this study, the authors identify P. copri strains with a 100kbp transposon unique to the microbiome of individuals with RA, which could enhance arthritis in murine models.

Article  CAS  PubMed  Google Scholar 

Ansaldo E, Farley TK, Belkaid Y. Control of immunity by the microbiota. Annu Rev Immunol. 2021;39(1):449–79.

Article  CAS  PubMed  Google Scholar 

Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013;5(193):193ra91-ra91.

Article  PubMed  PubMed Central  Google Scholar 

Pongratz G, Lowin T, Sewerin P, Zaucke F, Jenei-Lanzl Z, Pauly T, et al. Tryptophan metabolism in rheumatoid arthritis is associated with rheumatoid factor and predicts joint pathology evaluated by the rheumatoid arthritis MRI score (RAMRIS). Clin Exp Rheumatol. 2019;37(3):450–7.

PubMed  Google Scholar 

Li J, Che N, Xu L, Zhang Q, Wang Q, Tan W, et al. LC-MS-based serum metabolomics reveals a distinctive signature in patients with rheumatoid arthritis. Clin Rheumatol. 2018;37(6):1493–502.

Article  PubMed  Google Scholar 

Labadarios D, McKenzie DY, Dickerson JWT, Parke DV. Metabolic abnormalities of tryptophan and nicotinic acid in patients with rheumatoid arthritis. Rheumatology. 1978;17(4):227–32.

Article  CAS  Google Scholar 

Schroecksnadel K, Kaser S, Ledochowski M, Neurauter G, Mur E, Herold M, et al. Increased degradation of tryptophan in blood of patients with rheumatoid arthritis. J Rheumatol. 2003;30(9):1935–9.

CAS  PubMed  Google Scholar 

Forrest CM, Kennedy A, Stone TW, Stoy N, Darlington LG. Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis during drug treatment. Adv Exp Med Biol. 2003;527:287–95.

Article  CAS  PubMed  Google Scholar 

Yu D, Du J, Pu X, Zheng L, Chen S, Wang N, et al. The gut microbiome and metabolites are altered and interrelated in patients with rheumatoid arthritis. Front Cell In