2005;307(5717):191520. No use, distribution or reproduction is permitted which does not comply with these terms. Interestingly, very high-dose vitamin D diet is unexpectedly associated with an increase in Bacteroidetes, particularly of the orders Bacteroidales and Flavobacteriale, with a decrease in circulating vitamin D [51], suggesting that vitamin D may influence host systematic immunology by modifying the diversity of gut microbiota in a complex feedback loop. This study was supported by National Natural Science Foundation of China (Grant No. It is well accepted that gut microbiota have been shown to produce a wide range of molecules, including enzymes, short-chain fatty acids (SCFAs), and metabolites. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Thomas AC, Hubbard-Turner T, Wikstrom EA, Palmieri-Smith RM. Ghaly S, Kaakoush NO, Lloyd F, McGonigle T, Mok D, Baird A, Klopcic B, Gordon L, Gorman S, Forest C, et al. Probiotic treatment has been shown to promote bone metabolism, reduce pain and inflammatory responses of age-related musculoskeletal disorders, including OA. Jenks K, Stebbings S, Burton J, Schultz M, Herbison P, Highton J. Probiotic therapy for the treatment of spondyloarthritis: a randomized controlled trial. In particular, the combination of the two interventions resulted in an increased relative abundance of Bifidobacterium and Roseburia negatively associated with knee joint damage induced by diet-induced obesity while a decrease in Clostridium leptum (cluster IV) and Akkemansia muciniphila which exhibited a positive association with joint damage. Also, dietary glutamine supplementation alters composition and metabolism of intestinal microbiota, inducing a shift in the Firmicutes/Bacteroidetes ratio and enhanced intestinal secretory IgA (SIgA) secretion [53]. 2015;112(33):1047984. Google Scholar. Ageing Res Rev. The effects of vitamin D on Bacteroides phylum are not conclusive while some studies have reported that a low vitamin D diet or vitamin D receptor (VDR) knock-out results in a more inflammatory fecal microbiome characterized by an increased Bacteroidetes [49, 50]. 2011;88(78):35866. Furthermore, these alterations in centenarians are associated with increased levels of proinflammatory markers, suggesting the potential role of gut microbiota in this pervasive systematic inflammation [32]. Gut microbiota and aging. The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: a systematic review of randomized human clinical trials. This adds another layer of complexity to the mechanisms of gut microbiota. Still, no evidence supports the role of genetic susceptibility of VDR gene in the interaction between host and gut microbiota on OA onset and progression while we believe that this critical gene in bone and joint health may contribute to the individual difference of OA patients by the involvement in host-gut interaction. 2013;21(1):7990. Lee SH, Yun Y, Kim SJ, Lee EJ, Chang Y, Ryu S, Shin H, Kim HL, Kim HN, Lee JH. The authors declared no conflict of interests about the publication of this paper. Thomas S, Browne H, Mobasheri A, Rayman MP. Both these autoimmune conditions have been associated with altered intestinal microbiota, but the relationship between dysbiosis and the pathogenesis of the disease is not completely clear. Rheumatic diseases are frequent chronic inflammatory conditions often involving autoimmune processes. Inflammation. Osteoarthr Cartil. Along with these natural treatment options, probiotics and prebiotic strains have been shown to help with arthritis inflammation. With aging and increasing obesity population, the prevalence of osteoarthritis is rising, particularly since the mid-twentieth century, impacting 303 million individuals globally in 2017 and resulting in unsustainable clinical, humanistic, and economic burdens composed of medical care costs, lost wages, and depressed economic productivity [2,3,4]. Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, et al.. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. For instance, Biagi et al. 2018;21(4):36471. 2014;5(3):40410. Dobson GP, Letson HL, Grant A, McEwen P, Hazratwala K, Wilkinson M, Morris JL. Ooi JH, Li Y, Rogers CJ, Cantorna MT. Liu et al. 2016;48(4):90714. 1995;38(8):113441. 2016;45(4 Suppl):S127. A pilot non-controlled study carried out on 18 patients with SpA associated with ulcerative colitis showed that a combination of L. acidophilus and L. salivarius ameliorate SpA through a reduction in disease activity and patients' perception of pain (26). Moreover, gut microbiota is also the potential biomarker related to inflammation and gut dysbiosis that is able to predict OA progression and monitor the efficacy of therapeutic intervention. However, their promising anti-inflammatory and immunomodulating properties are worth to be investigated by larger population studies, in order to identify their possible functional interest in supporting standard therapies and disease activity control in rheumatic diseases. According to a new study that scientists carried out in rodents, probiotics might be an effective way to prevent the bone loss that leads to osteoporosis. Careers, Unable to load your collection due to an error. The only trial conducted over a longer period (12 weeks) involved twenty-nine patients with RA and showed that a combination of L. rhamnosus GR-1 and L. reuteri RC-14 lead to a significant improvement in the Health Assessment Questionnaire (HAQ) score in the probiotic group but did not clinically improve RA (12). Osteoarthr Cartil. Association Between Gut Microbiota and Osteoarthritis: A Review of Evidence for Potential Mechanisms and Therapeutics. Baker KR, Matthan NR, Lichtenstein AH, Niu J, Guermazi A, Roemer F, Grainger A, Nevitt MC, Clancy M, Lewis CE, et al. Solovieva S, Hirvonen A, Siivola P, Vehmas T, Luoma K, Riihimaki H, Leino-Arjas P. Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women. 2015;50(2):26173. Previous studies have showed that the intake of dietary antioxidants such as vitamin C, D, and K, involved in regulating collagen formation, bone metabolism, and cartilage mineralization, may prevent the progression of OA [44]. HHS Vulnerability Disclosure, Help Rios JL, Bomhof MR, Reimer RA, Hart DA, Collins KH, Herzog W. Protective effect of prebiotic and exercise intervention on knee health in a rat model of diet-induced obesity. In particular, dysbiosis has been postulated as a causal factor in the initiation and propagation of obesity-associated OA (21). Clinical, humanistic, and economic burden of osteoarthritis among noninstitutionalized adults in the United States. J Med Food. PubMed Central showed that taxonomic shifts included an enriched abundance of Akkermansia and a decrease in Proteobacteria after 6-week exercise among previously sedentary overweight women [83]. These findings support that an adverse microbiome would exacerbate the histopathological severity of OA induced by joint injury in a murine model. Other possible mechanisms of actions may include the modulation of tryptophan metabolism and adenosine signaling as observed in other models (42, 43). Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced colitis. Osteoarthritis (OA) is a highly heterogeneous joint disease characterized by joint pain and a progressive loss of articular cartilage. PubMed Central observed that the structure of the gut microbiota of centenarians differs significantly from that of non-centenarian adults, characterized by an enrichment in Proteobacteria, a phylum including many potentially pathogenic bacteria. 2018;26(8):1098109. According to a new study that scientists carried out in rodents, probiotics might be an effective way to prevent the bone loss that leads to osteoporosis. 2009;121(6):920. Some foods and supplements also contain probiotics. J Athl Train. WebProbiotics and Arthritis. Collins et al. Arthritis Research & Therapy 2017;2017:3831972. It is a striking observation that females are at greater risk for developing knee, hip, and hand OA compared to males and tend to be more severe [33]. Association Between Gut Microbiota and Osteoarthritis: A Review of Evidence for Potential Mechanisms and Therapeutics. Using mouse models of SLE some authors have demonstrated that probiotic supplementation ameliorates disease activity, Treg regulation, and typical comorbidities occurring in SLE including cardiovascular complications (27, 28). It has been known for some time that the role of the central nervous system (CNS) is related to chronic pain in OA patients [58]. High dose vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis. 2016;12(2):1239. The Pros and Cons of Probiotics for Rheumatoid and Psoriatic Arthritis. Osteoarthr Cartil. Another trial confirmed the inefficacy of probiotics in systemic sclerosis associated gastrointestinal disease but SSc clinical outcomes were not addressed in that study (30). WebThere is pre-clinical evidence that probiotics have anti-inflammatory effects and protect against ovariectomy-induced bone loss and that they restore microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis . Body mass index and hand osteoarthritis susceptibility: an updated meta-analysis. Li Y, Xiao W, Luo W, Zeng C, Deng Z, Ren W, Wu G, Lei G. Alterations of amino acid metabolism in osteoarthritis: its implications for nutrition and health. Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S, Consolandi C, Quercia S, Scurti M, Monti D, et al. So JS, Lee CG, Kwon HK, Yi HJ, Chae CS, Park JA, et al.. Cell Host Microbe. Butyrate has demonstrated to suppress antigen-induced arthritis in mice by affecting both B and T cell development. FOIA It is likely that gut microbiota influences joint by regulating inflammation and metabolism, while the gap between cartilage metabolism and gut microbiota still exists. The degradation of glycosaminoglycans by intestinal microflora deteriorates colitis in mice. Vitamin D and calcium work together in the body to build and preserve bone health, which is important for both osteoarthritis and rheumatoid arthritis. Briefly, CNS modulates the gastrointestinal tract and enteric nervous system through sympathetic and parasympathetic axis while intestinal microbiota influence CNS function through vagal afferent nerves, immune system, HPA axis, and bacterially derived neurotransmitters [61, 62]. Rheumatology. Ageing and the pathogenesis of osteoarthritis. Centers for Disease C, Prevention. 2009;32(1):2736. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Keywords: probiotics, gut microbiota, Lactobacillus, Bifidobacterium, rheumatoid arthritis. Berenbaum F, Wallace IJ, Lieberman DE, Felson DT. So far, the new components of the CNS theory in OA pathophysiology include hypothalamic-pituitary (HPA) axis, nucleus tractus solitarus (NTS), hypothalamic suprachiasmatic nuclei (SCN), and other associated higher centers, and each with their own feedback circuits from the gut microbiota, OA joints, and cellular metabolism. demonstrated that oral supplementation with green-lipped mussel extract or glucosamine sulfate have symptom-modulating effects on OA patients by regulating the composition, metabolic, and immunological activities of gut microbiota [19]. Although the low population size, the treatment led to a greater improvement in pain scale, patient global assessment, self-assessed disability, and serum C-reactive protein (CRP) biomarker compared with subjects randomized to placebo. 2016;12(7):41220. Among them, inflammatory chronic diseases including rheumatoid arthritis (RA), spondyloarthritis (SpA), crystal-induced arthritis (CIA), and connective tissue autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), are the most common. According to a new study that scientists carried out in rodents, probiotics might be an effective way to prevent the bone loss that leads to osteoporosis. Moreover, some possible conjectures also have been proposed for explaining the discrepancy of gender-dependent influence in OA, such as sex differences in gut microbiota composition [35]. Still, the knowledge of the interactions between the OA-relevant factors and gut microbiota adds a novel layer of our understanding of the complexity of OA pathogenesis and also provides a new perspective on OA investigation. Concerning probiotics, the results of the RCTs discussed above are still limited to firmly conclude their effect in improving disease activity or progression, and even less in preventing disease development. and transmitted securely. PubMed Another observation performed by Guss et al. PubMed Central Of interest, the activation of adenosine receptors by specific probiotic stains is implicated in the suppressive effect of Treg toward T effector cells (Th1-Th2-Th17) (43) and might reinforce their beneficial role in autoimmune diseases. 2015;125(3):92638. Cell Mol Life Sci. Exercise alters gut microbiota composition and function in lean and obese humans. Arthritis Res Ther 23, 42 (2021). Mechanisms Underlying Probiotics Effects on Gut Microbiota, Immune System and Rheumatoid Arthritis. ), and Streptococci (S.), either as single species or in mixed culture. Mediat Inflamm. Does lipopolysaccharide-mediated inflammation have a role in OA? Google Scholar. As a library, NLM provides access to scientific literature. 2019;76(3):47393. Overall, the effect of probiotic supplementation in RA leads to a general benefit to the patients at least in the short term. Moreover, it is important to point out that this systematic low-degree inflammation induced by the disturbed gut microbiota is not specific for OA but rather favors the emergence of several potential diseases, such as metabolic syndrome and cardiovascular diseases. Amino Acids. Del Pinto R, Ferri C, Cominelli F. Vitamin D Axis in Inflammatory Bowel Diseases: Role, Current Uses and Future Perspectives. In this context, the improved understanding of how these dietary factors contribute to the maintenance of joint fitness is helpful to interpret the association between OA and unfavorable diet and give promise to diet-based supplemental strategies. European consensus conference on faecal microbiota transplantation in clinical practice. Cammarota G, Ianiro G, Tilg H, Rajilic-Stojanovic M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, et al. was the first to find that exercise increases gut microbial diversity that was positively correlated with dietary protein consumption in the athlete group [85]. Gout is a frequent rheumatic disease caused by the precipitation of pro-inflammatory monosodium urate crystals in the joint. This study aims to examine the effects of probiotics on pain hypersensitivity at the end of a six-week intervention program in patients with osteoarthritis (OA)-related pain. 2006;8(1):R20. Sci Rep. 2019;9(1):3893. The therapeutic potential of using probiotics to treat OA has only recently been recognized, with a small number of animal and human studies having been undertaken. The different composition of gut microbiota between males and females may be mediated by sex hormones. Patients and methods This double-blind randomized controlled clinical trial with two parallel arms will be conducted between January 2021 and July 2022. Int J Biol Macromol. In the context, we also speculated the promising manipulation of gut microbiota in OA management, such as exercise and fecal microbiota transplantation (FMT), highlighting the clinical values of gut microbiota. Probiotics are healthy bacteria commonly found in dairy foods like yogurt and kefir. Gut Microbes. CAS Probiotics. These risk factors independently or intricately contribute to a complex interaction between mechanical, biochemical, and cellular factors, leading to the pathogenesis of OA. Considering the growing global prevalence of OA, effective disease-modifying therapeutic strategy for relieving symptoms and slowing down OA progress are greatly needed. Visser AW, Ioan-Facsinay A, de Mutsert R, Widya RL, Loef M, de Roos A, le Cessie S, den Heijer M, Rosendaal FR, Kloppenburg M, et al. It has been observed that healthy dietary habits and the consumption of foods rich in bioactive compounds, omega-3 fatty acids, and antioxidants are associated with a lower risk to develop these diseases and a less severe clinical outcome (3). The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis. 2017;14(8):491502. This capacity to induce immune tolerance have been also associated to a reduced pathogenic humoral immune response in the mouse model of collagen-induced arthritis where the oral feeding of animals with L. Casei Shirota suppressed the abnormal antibody production evocated by type 2 collagen immunization (39). An increase polarization toward a T regulatory (Treg) phenotype with a decrease in Th17 cell has been observed in a different animal model of RA along with the inhibition of pro-inflammatory cytokines (34). SCFA including butyrate, acetate, and propionate, are microbiota metabolites deriving from intestinal bacteria fermentation of dietary fibers. Additionally, due to the findings of Liang et al. Huang Z, Chen J, Li B, Zeng B, Chou CH, Zheng X, Xie J, Li H, Hao Y, Chen G, et al. showed that prebiotic fiber supplementation, aerobic exercise, and the combination of these two interventions completely prevented the development of OA-like knee joint damage in a high-fat/high-sucrose diet-induced rat model of obesity [20]. Obesity is an established risk factor for osteoarthritis not only in weight-bearing joints, such as knee and hip, but also in non-weight-bearing joints, such as hand and temporomandibular joints, indicating that obesity contribute to the systemic factors relevant to OA [54, 55]. The gut-joint axis is established on the possibility of the crosstalk between joint and gut. Munukka E, Ahtiainen JP, Puigbo P, Jalkanen S, Pahkala K, Keskitalo A, Kujala UM, Pietila S, Hollmen M, Elo L, et al. WebBenefits 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. 2016;7:51. Guss JD, Ziemian SN, Luna M, Sandoval TN, Holyoak DT, Guisado GG, Roubert S, Callahan RL, Brito IL, van der Meulen MCH, et al. Precision Nutrition and the Microbiome, Part I: Current State of the Science. Cookies policy. This is of particular interest given that the Th1-Th17 response play an important role in the initial phase of the development of autoimmune disorders, including autoimmune rheumatic diseases. Methods: The study was an N-of-1 trial design, divided into 3 blocks of 10 weeks. A link between the composition and activity of GM and human health and disease has been previously described (Azad, Sarker, Li, et al., 2018). Although still limited, there's a growing interest in the possible use of probiotics in rheumatic diseases. Progression of OA is increasingly linked to dysregulation of central feedback circuits (e.g., HPA axis and NTS), which control circadian rhythm, gut microbiome, metabolism, and redox regulation [60]. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Probiotics are composed of live microorganisms, generally lactic acid bacteria, which play a crucial part in the maintenance of healthy gut microbiota homeostasis by promoting the production of antimicrobial substances and immunoglobulins and inhibiting the production of bacterial toxins [70]. Schott et al. Beyond the impact of post-injury inflammation responses on cartilage and subchondral bone, a direct correlation between gut microbiota and development of injury-induced OA has been previously demonstrated.
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