Emerging data implicate the human microbiome in the pathogenesis of inflammatory arthritides
Mucosal sites exposed to high load of bacterial antigens (i.e. gut) may represent the initial site of tolerance break in rheumatoid arthritis, psoriatic arthritis and related diseases
Microbial and dietary metabolites (e.g. SCFAs and MCFAs) have immunomodulatory properties that could be exploited for the treatment of rheumatic disorders
Pharmacomicrobiomics is a novel field of research that investigates the effect of variations within the human microbiome on drugs and could facilitate precision medicine in cancer and autoimmunity
The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host–microorganism interaction is likely to go well beyond taxonomic, correlative observations. In fact, most advances in the field relate to the functional and metabolic capabilities of these microorganisms and their influence on mucosal immunity and systemic inflammation. An intricate relationship between the microbiome and the diet of the host is now fully recognized, with the microbiota having an important role in the degradation of polysaccharides into active metabolites. This Review summarizes the current knowledge on the metabolic role of the microbiota in health and rheumatic disease, including the advances in pharmacomicrobiomics and its potential use in diagnostics, therapeutics and personalized medicine.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Induction mechanism of cigarette smoke components (CSCs) on dyslipidemia and hepatic steatosis in rats
Lipids in Health and Disease Open Access 08 November 2022
The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis
Nature Communications Open Access 05 April 2019
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
The Human Microbiome Consortium Project. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).
Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).
Abdollahi-Roodsaz, S. et al. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J. Clin. Invest. 118, 205–216 (2008).
Scher, J. U. & Abramson, S. B. The microbiome and rheumatoid arthritis. Nat. Rev. Rheumatol. 7, 569–578 (2011).
Wu, H. J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815–827 (2010).
Brown, J. M. & Hazen, S. L. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu. Rev. Med. 66, 343–359 (2015).
Kriegel, M. A. et al. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc. Natl Acad. Sci. USA 108, 11548–11553 (2011).
Ochoa-Reparaz, J. et al. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J. Immunol. 183, 6041–6050 (2009).
Clarke, G. et al. Minireview: gut microbiota: the neglected endocrine organ. Mol. Endocrinol. 28, 1221–1238 (2014).
Chung, H. et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell 149, 1578–1593 (2012).
Sharon, G. et al. Specialized metabolites from the microbiome in health and disease. Cell Metab. 20, 719–730 (2014).
Said, H. M. Intestinal absorption of water-soluble vitamins in health and disease. Biochem. J. 437, 357–372 (2011).
Bercik, P. et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141, 599–609.e1 (2011).
Love, T. J. et al. Obesity and the risk of psoriatic arthritis: a population-based study. Ann. Rheum. Dis. 71, 1273–1277 (2012).
Lu, B. et al. Being overweight or obese and risk of developing rheumatoid arthritis among women: a prospective cohort study. Ann. Rheum. Dis. 73, 1914–1922 (2014).
Gremese, E., Tolusso, B., Gigante, M. R. & Ferraccioli, G. Obesity as a risk and severity factor in rheumatic diseases (autoimmune chronic inflammatory diseases). Front. Immunol. 5, 576 (2014).
Thorburn, A. N., Macia, L. & Mackay, C. R. Diet, metabolites, and 'western-lifestyle' inflammatory diseases. Immunity 40, 833–842 (2014).
Cox, L. M. et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705–721 (2014).
Samuel, B. S. et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl Acad. Sci. USA 105, 16767–16772 (2008).
Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011).
Topping, D. L. & Clifton, P. M. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 81, 1031–1064 (2001).
Macia, L. et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6, 6734 (2015).
Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).
Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic TREG cell homeostasis. Science 341, 569–573 (2013).
Maslowski, K. M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286 (2009).
Vieira, A. T. et al. A role for gut microbiota and the metabolite-sensing receptor GPR43 in a murine model of gout. Arthritis Rheumatol. 67, 1646–1656 (2015).
Cleophas, M. C. et al. Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases. Ann. Rheum. Dis. 75, 593–600 (2016).
Liberato, M. V. et al. Medium chain fatty acids are selective peroxisome proliferator activated receptor (PPAR) γ activators and pan-PPAR partial agonists. PLoS ONE 7, e36297 (2012).
Bassaganya-Riera, J. et al. Probiotic bacteria produce conjugated linoleic acid locally in the gut that targets macrophage PPARγ to suppress colitis. PLoS ONE 7, e31238 (2012).
Bassaganya-Riera, J. et al. Conjugated linoleic acid modulates immune responses in patients with mild to moderately active Crohn's disease. Clin. Nutr. 31, 721–727 (2012).
Scher, J. U. et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 67, 128–139 (2015).
De Preter, V. et al. Faecal metabolite profiling identifies medium-chain fatty acids as discriminating compounds in IBD. Gut 64, 447–458 (2015).
Asquith, M. S. et al. HLA-B27 expression profoundly shapes the host-microbiota metabolome [abstract 2097]. Arthritis Rheumatol. 67 (Suppl. S10), S2504–S2505 (2015).
Liu, H. X., Keane, R., Sheng, L. & Wan, Y. Y. Implications of microbiota and bile acid in liver injury and regeneration. J. Hepatol. 63, 1502–1510 (2015).
Schaap, F. G., Trauner, M. & Jansen, P. L. Bile acid receptors as targets for drug development. Nat. Rev. Gastroenterol. Hepatol. 11, 55–67 (2014).
Kim, I. et al. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 28, 940–946 (2007).
Triantis, V., Saeland, E., Bijl, N., Oude-Elferink, R. P. & Jansen, P. L. Glycosylation of fibroblast growth factor receptor 4 is a key regulator of fibroblast growth factor 19-mediated down-regulation of cytochrome P450 7A1. Hepatology 52, 656–666 (2010).
Watanabe, M. et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439, 484–489 (2006).
Pols, T. W. et al. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading. Cell Metab. 14, 747–757 (2011).
Ali, A. H., Carey, E. J. & Lindor, K. D. Recent advances in the development of farnesoid X receptor agonists. Ann. Transl. Med. 3, 5 (2015).
Buzzetti, E., Pinzani, M. & Tsochatzis, E. A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism http://dx.doi.org/10.1016/j.metabol.2015.12.012 (2016).
Malhotra, N. & Beaton, M. D. Management of non-alcoholic fatty liver disease in 2015. World J. Hepatol. 7, 2962–2967 (2015).
Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).
Boursier, J. et al. The severity of NAFLD is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 63, 764–775 (2016).
Miele, L. et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 49, 1877–1887 (2009).
Rivera, C. A. et al. Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis. J. Hepatol. 47, 571–579 (2007).
Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).
Farhadi, A. et al. Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non-alcoholic steatohepatitis. Liver Int. 28, 1026–1033 (2008).
Dumas, M. E. et al. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc. Natl Acad. Sci. USA 103, 12511–12516 (2006).
Koeth, R. A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576–585 (2013).
Federico, A., Dallio, M., Godos, J., Loguercio, C. & Salomone, F. Targeting gut–liver axis for the treatment of nonalcoholic steatohepatitis: translational and clinical evidence. Transl. Res. 167, 116–124 (2016).
Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).
Tang, W. H. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013).
Riddle, J. M. A History of the Middle Ages, 300–1500 (Rowman & Littlefield Publishers, 2008).
Di Giuseppe, D., Crippa, A., Orsini, N. & Wolk, A. Fish consumption and risk of rheumatoid arthritis: a dose-response meta-analysis. Arthritis Res. Ther. 16, 446 (2014).
Di Giuseppe, D., Alfredsson, L., Bottai, M., Askling, J. & Wolk, A. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study. BMJ 345, e4230 (2012).
Jin, Z., Xiang, C., Cai, Q., Wei, X. & He, J. Alcohol consumption as a preventive factor for developing rheumatoid arthritis: a dose-response meta-analysis of prospective studies. Ann. Rheum. Dis. 73, 1962–1967 (2014).
Di Minno, M. N. et al. Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor α blockers. Ann. Rheum. Dis. 73, 1157–1162 (2014).
McKellar, G. et al. A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow. Ann. Rheum. Dis. 66, 1239–1243 (2007).
Skoldstam, L., Hagfors, L. & Johansson, G. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann. Rheum. Dis. 62, 208–214 (2003).
Hu, Y. et al. Mediterranean diet and incidence of rheumatoid arthritis in women. Arthritis Care Res. (Hoboken) 67, 597–606 (2015).
Lu, B., Solomon, D. H., Costenbader, K. H. & Karlson, E. W. Alcohol consumption and risk of incident rheumatoid arthritis in women: a prospective study. Arthritis Rheumatol. 66, 1998–2005 (2014).
Hagfors, L., Nilsson, I., Skoldstam, L. & Johansson, G. Fat intake and composition of fatty acids in serum phospholipids in a randomized, controlled, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr. Metab. (Lond.) 2, 26 (2005).
Hagfors, L., Leanderson, P., Skoldstam, L., Andersson, J. & Johansson, G. Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr. J. 2, 5 (2003).
Wu, G. D. et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut 65, 63–72 (2016).
De Filippis, F. et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut http://dx.doi.org/10.1136/gutjnl-2015-309957 (2015).
Rosell, M. et al. Dietary fish and fish oil and the risk of rheumatoid arthritis. Epidemiology 20, 896–901 (2009).
Linos, A. et al. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? Am. J. Clin. Nutr. 70, 1077–1082 (1999).
Shapiro, J. A. et al. Diet and rheumatoid arthritis in women: a possible protective effect of fish consumption. Epidemiology 7, 256–263 (1996).
Fortin, P. R. et al. Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J. Clin. Epidemiol. 48, 1379–1390 (1995).
Proudman, S. M. et al. Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann. Rheum. Dis. 74, 89–95 (2015).
Lee, Y. H., Bae, S. C. & Song, G. G. Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis. Arch. Med. Res. 43, 356–362 (2012).
Serhan, C. N., Chiang, N. & van Dyke, T. E. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol. 8, 349–361 (2008).
Norling, L. V. & Perretti, M. The role of omega-3 derived resolvins in arthritis. Curr. Opin. Pharmacol. 13, 476–481 (2013).
Rosillo, M. A. et al. Dietary extra-virgin olive oil prevents inflammatory response and cartilage matrix degradation in murine collagen-induced arthritis. Eur. J. Nutr. 55, 315–325 (2016).
Silva, S. et al. Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis. J. Nutr. Biochem. 26, 360–368 (2015).
Caesar, R., Tremaroli, V., Kovatcheva-Datchary, P., Cani, P. D. & Backhed, F. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 22, 658–668 (2015).
Cerhan, J. R. et al. Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. Am. J. Epidemiol. 157, 345–354 (2003).
Pattison, D. J. et al. Dietary risk factors for the development of inflammatory polyarthritis: evidence for a role of high level of red meat consumption. Arthritis Rheum. 50, 3804–3812 (2004).
Benito-Garcia, E., Feskanich, D., Hu, F. B., Mandl, L. A. & Karlson, E. W. Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study. Arthritis Res. Ther. 9, R16 (2007).
Morris, C. J. et al. Relationship between iron deposits and tissue damage in the synovium: an ultrastructural study. Ann. Rheum. Dis. 45, 21–26 (1986).
Tsuda, R. et al. Monoclonal antibody against citrullinated peptides obtained from rheumatoid arthritis patients reacts with numerous citrullinated microbial and food proteins. Arthritis Rheumatol. 67, 2020–2031 (2015).
Alipour, B. et al. 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. 17, 519–527 (2014).
Hatakka, K. et al. Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis — a pilot study. Scand. J. Rheumatol. 32, 211–215 (2003).
Pineda Mde, L. et al. A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Med. Sci. Monit. 17, CR347–CR354 (2011).
Allen, S. J. The potential of probiotics to prevent Clostridium difficile infection. Infect. Dis. Clin. North Am. 29, 135–144 (2015).
Bejaoui, M., Sokol, H. & Marteau, P. Targeting the microbiome in inflammatory bowel disease: critical evaluation of current concepts and moving to new horizons. Dig. Dis. 33 (Suppl. 1), 105–112 (2015).
van Nood, E. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).
Kelly, C. R. et al. Update on fecal microbiota transplantation 2015: indications, methodologies, mechanisms, and outlook. Gastroenterology 149, 223–237 (2015).
Youngster, I. et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 312, 1772–1778 (2014).
Bennet, J. D. & Brinkman, M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet 1, 164 (1989).
Borody, T. J. et al. Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Med. J. Aust. 150, 604 (1989).
Colman, R. J. & Rubin, D. T. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J. Crohns Colitis 8, 1569–1581 (2014).
Moayyedi, P. et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109.e6 (2015).
Rossen, N. G. et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149, 110–118.e4 (2015).
Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).
Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500, 232–236 (2013).
Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).
Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).
Shen, Y. et al. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12, 509–520 (2012).
Garber, K. Drugging the gut microbiome. Nat. Biotechnol. 33, 228–231 (2015).
Ratner, M. Microbial cocktails join fecal transplants in IBD treatment trials. Nat. Biotechnol. 33, 787–788 (2015).
Olle, B. Medicines from microbiota. Nat. Biotechnol. 31, 309–315 (2013).
Rizkallah, M. R. S., R. & Aziz, R. K. The Human Microbiome Project, personalized medicine and the birth of pharmacomicrobiomics. Curr. Pharmacogenomics Person. Med. 8, 182–193 (2010).
Lindenbaum, J. et al. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N. Engl. J. Med. 305, 789–794 (1981).
Haiser, H. J. et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341, 295–298 (2013).
Niehues, M. & Hensel, A. In-vitro interaction of L-Dopa with bacterial adhesins of Helicobacter pylori: an explanation for clinicial differences in bioavailability? J. Pharm. Pharmacol. 61, 1303–1307 (2009).
LoGuidice, A., Wallace, B. D., Bendel, L., Redinbo, M. R. & Boelsterli, U. A. Pharmacologic targeting of bacterial β-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice. J. Pharmacol. Exp. Ther. 341, 447–454 (2012).
Bjorkholm, B. et al. Intestinal microbiota regulate xenobiotic metabolism in the liver. PLoS ONE 4, e6958 (2009).
Craciun, S. & Balskus, E. P. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc. Natl Acad. Sci. USA 109, 21307–21312 (2012).
Nakayama, H. et al. Intestinal anaerobic bacteria hydrolyse sorivudine, producing the high blood concentration of 5-(E)-(2-bromovinyl)uracil that increases the level and toxicity of 5-fluorouracil. Pharmacogenetics 7, 35–43 (1997).
Clayton, T. A., Baker, D., Lindon, J. C., Everett, J. R. & Nicholson, J. K. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc. Natl Acad. Sci. USA 106, 14728–14733 (2009).
Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971–976 (2013).
Saad, R., Rizkallah, M. R. & Aziz, R. K. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes. Gut Pathog. 4, 16 (2012).
Peppercorn, M. A. & Goldman, P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J. Pharmacol. Exp. Ther. 181, 555–562 (1972).
Maurice, C. F., Haiser, H. J. & Turnbaugh, P. J. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152, 39–50 (2013).
ElRakaiby, M. et al. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics. OMICS 18, 402–414 (2014).
van Roon, E. N. & van de Laar, M. A. Methotrexate bioavailability. Clin. Exp. Rheumatol. 28, S27–32 (2010).
Patterson, A. D. & Turnbaugh, P. J. Microbial determinants of biochemical individuality and their impact on toxicology and pharmacology. Cell Metab. 20, 761–768 (2014).
Dumas, M. E., Kinross, J. & Nicholson, J. K. Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease. Gastroenterology 146, 46–62 (2014).
Koen, N., Du Preez, I. & Loots du, T. Metabolomics and personalized medicine. Adv. Protein Chem. Struct. Biol. 102, 53–78 (2016).
Xia, J. & Wishart, D. S. MSEA: a web-based tool to identify biologically meaningful patterns in quantitative metabolomic data. Nucleic Acids Res. 38, W71–W77 (2010).
Reily, M. D. & Tymiak, A. A. Metabolomics in the pharmaceutical industry. Drug Discov. Today Technol. 13, 25–31 (2015).
S.A.-R. is supported by the Arthritis National Research Foundation (grant 15-A0-00-004310-01), the Netherlands Organization for Scientific Research (VENI grant 916.12.039) and the Dutch Arthritis Foundation (AFS 14-1-291 grant). S.B.A. is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) through the American Recovery and Reinvestment Act of 2009 (grant RC2 AR058986) and by The Colton Center for Autoimmunity. J.U.S. is supported by NIAMS (grant K23AR064318), the Arthritis Foundation (Innovative Research Grant), The Colton Center for Autoimmunity; and The Riley Family Foundation.
The authors declare no competing financial interests.
About this article
Cite this article
Abdollahi-Roodsaz, S., Abramson, S. & Scher, J. The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions. Nat Rev Rheumatol 12, 446–455 (2016). https://doi.org/10.1038/nrrheum.2016.68
This article is cited by
Induction mechanism of cigarette smoke components (CSCs) on dyslipidemia and hepatic steatosis in rats
Lipids in Health and Disease (2022)
Nature Reviews Drug Discovery (2021)
Nature Reviews Rheumatology (2021)
Probiotic Composition and Chondroitin Sulfate Regulate TLR-2/4-Mediated NF-κB Inflammatory Pathway and Cartilage Metabolism in Experimental Osteoarthritis
Probiotics and Antimicrobial Proteins (2021)
Nature Reviews Rheumatology (2020)