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      Ephedra sinica polysaccharide regulate the anti-inflammatory immunity of intestinal microecology and bacterial metabolites in rheumatoid arthritis

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          Abstract

          Introduction

          Ephedra sinica polysaccharide (ESP) exerts substantial therapeutic effects on rheumatoid arthritis (RA). However, the mechanism through which ESP intervenes in RA remains unclear. A close correlation has been observed between enzymes and derivatives in the gut microbiota and the inflammatory immune response in RA.

          Methods

          A type II collagen-induced arthritis (CIA) mice model was treated with Ephedra sinica polysaccharide. The therapeutic effect of ESP on collagen-induced arthritis mice was evaluated. The anti-inflammatory and cartilage-protective effects of ESP were also evaluated. Additionally, metagenomic sequencing was performed to identify changes in carbohydrate-active enzymes and resistance genes in the gut microbiota of the ESP-treated CIA mice. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to observe the levels of serum metabolites and short-chain fatty acids in the gut. Spearman’s correlational analysis revealed a correlation among the gut microbiota, antibiotic-resistance genes, and microbiota-derived metabolites.

          Results

          ESP treatment significantly reduced inflammation levels and cartilage damage in the CIA mice. It also decreased the levels of pro-inflammatory cytokines interleukin (IL)-6, and IL-1-β and protected the intestinal mucosal epithelial barrier, inhibiting inflammatory cell infiltration and mucosal damage. Here, ESP reduced the TLR4, MyD88, and TRAF6 levels in the synovium, inhibited the p65 expression and pp65 phosphorylation in the NF-κB signaling pathway, and blocked histone deacetylase (HDAC1 and HDAC2) signals. ESP influenced the gut microbiota structure, microbial carbohydrate-active enzymes, and microbial resistance related to resistance genes. ESP increased the serum levels of L-tyrosine, sn-glycero-3-phosphocholine, octadecanoic acid, N-oleoyl taurine, and decreased N-palmitoyl taurine in the CIA mice.

          Conclusion

          ESP exhibited an inhibitory effect on RA. Its action mechanism may be related to the ability of ESP to effectively reduce pro-inflammatory cytokines levels, protect the intestinal barrier, and regulate the interaction between mucosal immune systems and abnormal local microbiota. Accordingly, immune homeostasis was maintained and the inhibition of fibroblast-like synoviocyte (FLS) proliferation through the HDAC/TLR4/NF-κB pathway was mediated, thereby contributing to its anti-inflammatory and immune-modulating effects.

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          Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy

          Lukas Mager, Regula Burkhard, Nicola Pett … (2020)
          Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances anti-tumor immunity is unclear. Here, we isolated three bacterial species, including Bifidobacterium pseudolongum, Lactobacillus johnsonii and Olsenella species, that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated anti-tumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required co-stimulation. Collectively, our study identifies a novel microbial metabolite-immune pathway that is activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.
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            Gut-microbiota-targeted diets modulate human immune status

            Hannah Wastyk, Gabriela K. Fragiadakis, Dalia Perelman … (2021)
            Article 0 comments Cited 317 times – based on 0 reviews     Review now
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              The gut–joint axis in rheumatoid arthritis

              Mario Zaiss, Hsin-Jung Joyce Wu, Daniele Mauro … (2021)
              Article 0 comments Cited 100 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yanmiao Ma: URI : https://loop.frontiersin.org/people/2703459/overviewRole: Role: Role: Role:
                Xiuhong Wei: Role: Role: Role:
                Jiehao Peng: Role: Role: Role:
                Fuxia Wei: Role: Role:
                Ya Wen: Role: Role:
                Mingran Liu: Role: Role:
                Bo Song: Role:
                Yonghui Wang: Role: Role: Role: Role:
                Yumin Zhang: Role: Role: Role:
                Tao Peng: Role: Role: Role: Role:
                Journal
                Journal ID (nlm-ta): Front Pharmacol
                Journal ID (iso-abbrev): Front Pharmacol
                Journal ID (publisher-id): Front. Pharmacol.
                Title: Frontiers in Pharmacology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1663-9812
                Publication date (Electronic): 23 May 2024
                Publication date Collection: 2024
                Volume: 15
                Electronic Location Identifier: 1414675
                Affiliations
                [1] 1 Department of Basic Medical Sciences , Shanxi University of Chinese Medicine , Taiyuan, China
                [2] 2 Department of Third Clinical Medicine , Shanxi University of Chinese Medicine , Taiyuan, China
                [3] 3 Department of First Clinical Medicine , Shanxi University of Chinese Medicine , Taiyuan, China
                [4] 4 Famous Chinese Medicine Studio , Shanxi Hospital of Integrated Traditional Chinese and Western Medicine , Taiyuan, China
                [5] 5 Shanxi Provincial Key Laboratory of Classical Prescription Strengthening Yang , Shanxi Hospital of Integrated Traditional Chinese and Western Medicine Taiyuan , Taiyuan, China
                Author notes

                Edited by: Guang Wang, Jinan University, China

                Reviewed by: Jun-sheng Tian, Shanxi University, China

                Rong Zhang, Guangzhou University of Chinese Medicine, China

                Hong-he Xiao, Liaoning University of Traditional Chinese Medicine, China

                *Correspondence: Yanmiao Ma, mymsxtcm@ 123456sxtcm.edu.cn ; Tao Peng, pengtao5197220@ 123456163.com
                Article
                Publisher ID: 1414675
                DOI: 10.3389/fphar.2024.1414675
                PMC ID: 11153800
                PubMed ID: 38846095
                SO-VID: afac94c9-3f42-4ec9-a9c6-58735ba3052a
                Copyright © Copyright © 2024 Ma, Wei, Peng, Wei, Wen, Liu, Song, Wang, Zhang and Peng.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 09 April 2024
                Date accepted : 07 May 2024
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China Youth Project (#82104731), the Innovation Team for Traditional Chinese Medicine of the Health Commission of Shanxi Province (#ZYYTD2024026), the Scientific and Technological Innovation Team of Shanxi University of Chinese Medicine (#2022TD 2005).
                Categories
                Subject: Pharmacology
                Subject: Original Research
                Custom metadata
                section-at-acceptance Ethnopharmacology

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: rheumatoid arthritis,gut microbiota,systemic metabolism,tlr4/hdac/nf-κb pathway,ephedra sinica polysaccharide
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: rheumatoid arthritis, gut microbiota, systemic metabolism, tlr4/hdac/nf-κb pathway, ephedra sinica polysaccharide

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