Host-Microbiome Synergistic Control on Sphingolipid Metabolism by Mechanotransduction in Model Arthritis

Zhou, Xiaoyuan; Devescovi, Valentina; Liu, Yuanhua; Dent, Jennifer E.; Nardini, Christine

doi:10.3390/biom9040144

Cited by 6 publications

(3 citation statements)

References 54 publications

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“…108 The intracellular level of sphingolipid derivative sphingosine-1-phosphate (SIP) has been correlated to several inflammatory disorders, including RA. 109 Sphingolipid is converted to SIP by sphingosine kinase (Sphk 1/2). 110 Studies have shown that increase in the expression of ERK1/2, Akt, and TLR4 enhances the activity of Sphk1/2 and promotes the intracellular level of SIPs.…”

Section: Intracellular Signaling As Therapeutic Targets Of Ramentioning

confidence: 99%

Indigenous Nigeria medicinal herbal remedies: A potential source for therapeutic against rheumatoid arthritis

Arunsi

Chioma

Etusim

et al. 2022

Exp Biol Med (Maywood)

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Rheumatoid arthritis (RA) is a debilitating disease associated with locomotion impairment, and conventional therapeutic drugs are not optimal for managing RA. There is an avalanche of medications used for the management of RA. Still, studies have shown that they are associated with severe side effects, including hepatotoxicity, retinopathy, and cardiotoxicity disorders of the central nervous system (CNS), skin, blood, and infections. Complementary and alternative medicine (CAM) is currently gaining attention as a novel panacea for managing debilitating diseases, such as RA. Nigerian folk herbal remedies are replete with a plethora of curative medicine, albeit unvalidated scientifically but with seemingly miraculous provenance. Studies of the identification of bioactive compounds present in these botanicals using advanced spectral analytical techniques have enhanced our understanding of the role of Nigerian herbal remedies in the treatment and management of RA. Interestingly, experimental studies abound that the bioactive compounds present in the extracts of plant botanicals protected animals from the development of RA in different experimental models and reduced the toxicity associated with conventional therapeutics. Validated mechanisms of RA amelioration in human and animal models include suppression of the expression of NF-κB, IL-1β, TNF-α, IL-6, IL-8, IL-17, IL-23, chemokines, TGF-β, RANKL, RANK, iNOS, arginase, COX-2, VEGFA, VEGFR, NFATC1, and TRAP in the synoviocytes. Decreased ROS, NO, MDA, carbonyl groups, and PGE2 in the synovial fluid increased the expression of PPARα/γ; antioxidant and anti-inflammatory molecules also improve RA etiology. In this mini-review, we discuss the global burden of RA, the novel role of plant-based botanicals as potential therapeutics against signaling pathways in RA. Also addressed is the possible repurposing/reprofiling of plant botanicals to increase their therapeutic index among RA patients that patronize traditional healers in Nigeria with a global projection.

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Section: Intracellular Signaling As Therapeutic Targets Of Ramentioning

confidence: 99%

Indigenous Nigeria medicinal herbal remedies: A potential source for therapeutic against rheumatoid arthritis

Arunsi

Chioma

Etusim

et al. 2022

Exp Biol Med (Maywood)

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“…The CIA animal model is a common experimental animal model of RA that is established by immunization of animals with type II collagen, and this model has clinical features similar to those of human RA. The interplay between the gut microbiota and inflammatory arthritis in animal models has been demonstrated in vivo [ 82 ]. Previous studies reported that the alteration of the gut microbiota composition marked the preclinical phase of murine CIA and preceded the development of disease [ 83 , 84 ].…”

Section: Gut Microbiota and Metabolites In Ramentioning

confidence: 99%

Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis

Zhao

Fan

et al. 2020

Mediators of Inflammation

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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases caused by abnormal immune activation and immune tolerance. Immunomodulatory cells (ICs) play a critical role in the maintenance and homeostasis of normal immune function and in the pathogenesis of RA. The human gastrointestinal tract is inhabited by trillions of commensal microbiota on the mucosal surface that play a fundamental role in the induction, maintenance, and function of the host immune system. Gut microbiota dysbiosis can impact both the local and systemic immune systems and further contribute to various diseases, such as RA. The neighbouring intestinal ICs located in distinct intestinal mucosa may be the most likely intermediary by which the gut microbiota can affect the occurrence and development of RA. However, the reciprocal interaction between the components of the gut microbiota and their microbial metabolites with distinct ICs and how this interaction may impact the development of RA are not well studied. Therefore, a better understanding of the gut microbiota, ICs, and their interactions might improve our knowledge of the mechanisms by which the gut microbiota contribute to RA and facilitate the further development of novel therapeutic approaches. In this review, we have summarized the roles of the gut microbiota in the immunopathogenesis of RA, especially the interactions between the gut microbiota and ICs, and further discussed the strategies for treating RA by targeting/regulating the gut microbiota.

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“…Furthermore, the fecal transplantation from RA patients to germ-free arthritis-prone SKG mice induces the Th17 profile in the gut mucosa and severe RA, and when SKG dendritic cells were cultivated with Prevotella copri , there was an increased IL-17 response to RA autoantigens, suggesting that the gut microbes could induce autoreactive cells in the gut mucosa [14]. Interestingly, although MTX induces a decrease in bloodstream inflammation, MTX-treated CIA mice showed a decrease in microbial diversity, expansion of Prevotella spp., and no association with eubiotic microbiome [15,16].…”

Section: Introductionmentioning

confidence: 99%

Detection of Increased Relative Expression Units of Bacteroides and Prevotella, and Decreased Clostridium leptum in Stool Samples from Brazilian Rheumatoid Arthritis Patients: A Pilot Study

Rodrigues¹,

Cayres²,

Gonçalves³

et al. 2019

Microorganisms

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Interactions between gut microbes and disease modifying antirheumatic drugs (DMARDs) have been proposed. The aim of the present study was to evaluate the presence of some specific bacteria in stool samples from Brazilian RA patients receiving DMARDs and correlate these data with diet, clinical parameters, and cytokines. Stool samples were used for gut bacteria evalutation by qPCR. Serum samples were used to quantify IL-4 and IL-10 by flow cytometer. Statistics were performed by Pearson chi-square, Mann–Whitney U test, and Spearman’s correlation. The study included 20 RA patients and 30 healthy controls. There were no significant differences (p > 0.05) in dietary habits between RA patients and controls. Concerning gut bacteria, we observed an increase in relative expression units (REU) of Bacteroides and Prevotella species in stool samples from patients, and a decrease in REU of Clostridium leptum when compared with healthy controls. Positive correlation between Prevotella and rheumatoid factor was detected. The IL-4 and IL-10 concentrations were increased in patients when compared with controls. We concluded that gut bacteria are different between RA patients receiving DMARDs and healthy controls. Further studies are necessary to determine the real role of gut microbes and their metabolities in clinical response to different DMARDs in RA patients.

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Host-Microbiome Synergistic Control on Sphingolipid Metabolism by Mechanotransduction in Model Arthritis

Cited by 6 publications

References 54 publications

Indigenous Nigeria medicinal herbal remedies: A potential source for therapeutic against rheumatoid arthritis

Indigenous Nigeria medicinal herbal remedies: A potential source for therapeutic against rheumatoid arthritis

Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis

Detection of Increased Relative Expression Units of Bacteroides and Prevotella, and Decreased Clostridium leptum in Stool Samples from Brazilian Rheumatoid Arthritis Patients: A Pilot Study

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