OP0035 ASSESSMENT OF THE INTESTINAL PERMEABILITY IN PATIENTS WITH RHEUMATOID ARTHRITIS USING COLONIC TISSUES AND SERA

Background:Patients with rheumatoid arthritis (RA) have an altered gut microbiota (dysbiosis) (1-3). This microbiota interacts with intestinal epithelium which can lead to an increased intestinal permeability, responsible for the passage of antigens and inflammatory molecules, and can therefore promote systemic inflammation. Gut microbiota tends to normalize with disease control (2), suggesting that systemic inflammation may directly influence the composition of microbiota and the gut barrier. It was shown in many inflammatory diseases that intestinal permeability is impaired, but to date there is very little data in RA.Objectives:In the present study, we evaluate the intestinal permeability in RA patients by analyzing tight junctions in colonic biopsies and serum markers.Methods:Colonic biopsies from 20 RA patients who underwent coloscopy for screening with normal histology were compared with those from 20 age and sex matched controls. ZO-1, occludin and claudin 2 junction proteins were evaluated by immunohistochemistry. The staining intensity was assessed by two blinded independent readers. The serum concentrations of LPS-binding protein (LBP), CD14s and zonulin were evaluated by ELISA in 25 patients naive of DMARDs, 41 patients before and after introduction of a DMARDs and 21 controls. Elevated zonulin in serum indicates an increase in intestinal permeability while LBP and CD14s indicate bacterial translocation.Results:ZO-1 expression was significantly lower in biopsies from patients with RA than controls (mean score ± SD of 1.6 ± 0.56 vs 2.0 ± 0.43; p = 0.01). Age, sex, disease duration and immunological status did not significantly influence the expression of colonic junction proteins. LBP and CD14s were higher in serum from RA patients naive of DMARDs than controls (p = 0.002 and p = 0.003). LBP, CD14s and zonulin levels significantly correlated with DAS28 (r = 0.61, p = 0.005; r = 0.51, p = 0.030 and r = 0.46, p = 0.049, respectively). After treatment, unlike non-responders, LBP and CD14s were significantly reduced in DMARD responders and variations in LBP and CD14s significantly correlated with changes in DAS28 (r = 0.46, p = 0.002 and r = 0, 33 and p = 0.030, respectively).Conclusion:This work is one of the first to explore intestinal permeability in RA and to show altered tight junction in colonic tissue from RA. This increased intestinal permeability appears to be related to the systemic inflammation. Improving the gut microbiota through food or probiotics could enhance the effect of treatments by limiting this amplification loop of inflammation.References:[1]Horta-Baas G, Romero-Figueroa MDS, Montiel-Jarquin AJ, Pizano-Zarate ML, Garcia-Mena J, Ramirez-Duran N. Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis. J Immunol Res. 2017;2017:4835189.[2]Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895-905.[3]Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, et al. Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine. Arthritis Rheumatol. 2016;68(11):2646-61.Disclosure of Interests:Rachel Audo: None declared, Pauline Sanchez: None declared, Julie Mielle: None declared, Laurence Macia: None declared, Benjamin Rivière: None declared, Cédric Lukas: None declared, Bernard Combe: None declared, Jacques Morel: None declared, Claire Daien Speakers bureau: Pfizer roche chugai fresenius BMS msd Novartis galapagos, Consultant of: Abivax abbbvie BMS roche chugai, Grant/research support from: Pfizer, roche-chugai, fresenius, msd

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Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans

International Journal of Molecular Sciences ◽

10.3390/ijms22052331 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2331

Author(s):

Stephanie Lilja ◽

Carina Stoll ◽

Ulrike Krammer ◽

Berit Hippe ◽

Kalina Duszka ◽

...

Keyword(s):

Gut Microbiota ◽

Inflammatory Diseases ◽

Pyruvate Dehydrogenase Kinase ◽

Human Gut ◽

Mitochondrial Content ◽

Mt Dna ◽

Before And After ◽

Males And Females ◽

Sirt1 Gene ◽

Microbiota Diversity

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.

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Cumulative effect of systemic inflammation and oxidative stress in 40 known cases of active rheumatoid arthritis

International Journal of Research in Orthopaedics ◽

10.18203/issn.2455-4510.intjresorthop20160341 ◽

2015 ◽

Vol 1 (1) ◽

pp. 7 ◽

Cited By ~ 1

Author(s):

Rahul Saxena ◽

Shilpa Suneja ◽

Raj Saxena ◽

Dilutpal Sharma ◽

Alok Milton Lal

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Antioxidant Enzymes ◽

Systemic Inflammation ◽

Inflammatory Diseases ◽

Cumulative Effect ◽

Extensive Literature ◽

Reactive Protein ◽

Ceruloplasmin Level ◽

Student’S T

Background: Oxidative stress has been implicated in the pathophysiology of a number of diseases such as cancer, hypertension and inflammatory diseases. Although previous evidences provided extensive literature about the biological role of antioxidant enzymes in rheumatoid arthritis (RA), there is a paucity of satisfactory explanation regarding the alteration in the level of antioxidant enzymes along with marker of systemic inflammation in RA. The objective of present study was to estimate the level of C-reactive protein (CRP), Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GSHPx) and Ceruloplasmin in active RA patients.Methods: 40 patients of either sex (30-50 years age group) suffering from active RA and 40 normal healthy individuals served as control; were included in the study. Above mentioned parameters were estimated using standard methods and data from patients and controls were compared by using Student’s t-test.Results: Erythrocyte SOD, CAT and GSHPx activity were significantly low in RA subjects (P<0.001) whereas plasma Ceruloplasmin level was found to be significantly high (P<0.001) as compared to healthy controls.Conclusions: These findings suggest that combined effect of inflammation and free radical generation is involved in the pathogenesis of active RA, characterized by imbalance in antioxidant enzyme status and enhanced CRP levels, which served as an excellent marker of oxidative stress and systemic inflammation in active RA.

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Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

Mediators of Inflammation ◽

10.1155/2012/347268 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 24

Author(s):

Manuela Di Franco ◽

Francesca Romana Spinelli ◽

Alessio Metere ◽

Maria Chiara Gerardi ◽

Virginia Conti ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Endothelial Dysfunction ◽

Asymmetric Dimethylarginine ◽

Inflammatory Diseases ◽

Early Stage ◽

Serum Levels ◽

Joint Disease ◽

Baseline Serum ◽

Before And After ◽

Treatment Naïve

Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy.Methods. We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation.Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline(P=0.007)and significantly decreased after treatment (P=0.012versus controls). Baseline serum apelin levels were significantly decreased in this group (P=0.0001versus controls), but they were not significantly altered by treatment. IMT did not show significant changes.Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients.

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Effect of Moxibustion on HIF-1α and VEGF Levels in Patients with Rheumatoid Arthritis

Pain Research and Management ◽

10.1155/2019/4705247 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Yuanyuan Gong ◽

Zeyun Yu ◽

Yingni Wang ◽

Yan Xiong ◽

Yumei Zhou ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Treatment Group ◽

Clinical Symptoms ◽

Conventional Medicine ◽

Hypoxia Inducible Factor ◽

Serum Levels ◽

Serum Markers ◽

Control Group ◽

Analgesic Effects ◽

Before And After

Background. Moxibustion has a therapeutic effect of reducing swelling and relieving pain in patients with rheumatoid arthritis (RA) but its mechanism is uncertain. Objective. To evaluate the effect of moxibustion on serum levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients with RA and to explore the possible mechanism of moxibustion. Methods. This study involved 46 RA patients who had fulfilled the inclusion criteria and were randomly assigned to a treatment group and a control group in an equal ratio. The control group was treated with methotrexate or leflunomide, while the treatment group received methotrexate or leflunomide and moxibustion at ST 36 (Zusanli), BL 23 (Shenshu), and Ashi points. Patients’ clinical symptoms, RA-associated serum markers, and serum levels of TNF-α, IL-1β, HIF-1α, and VEGF were compared in the two groups before and after intervention. Statistical analysis was performed using SPSS 21.0 statistical software. Results. 37 of 46 RA patients eventually completed the whole treatment course. Compared with the control group, the treatment group significantly improved the clinical symptoms (P<0.05) but with no significant differences in RA-associated serum markers (P>0.05). There were significant differences in TNF-α and IL-1β among the groups after 8 weeks of treatment (P<0.05). HIF-1α and VEGF were decreased in the treatment group after therapy (P<0.05). VEGF was reduced in the control group (P<0.05), while HIF-1α was not significantly improved (P>0.05). The reductions of HIF-1α and VEGF in the treatment group were superior to the control group (P<0.05). Conclusions. Moxibustion enhanced the anti-inflammatory and analgesic effects of conventional medicine and can enhance the effect of conventional medicine, downregulating HIF-1α/VEGF contents to inhibit angiogenesis.

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Prevotella Copri and Microbiota in Rheumatoid Arthritis: Fully Convincing Evidence?

Journal of Clinical Medicine ◽

10.3390/jcm8111837 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1837 ◽

Cited By ~ 1

Author(s):

Drago

Keyword(s):

Rheumatoid Arthritis ◽

Immune System ◽

Gut Microbiota ◽

Inflammatory Diseases ◽

Convincing Evidence ◽

Immune Network ◽

Positive Balance ◽

Autoimmune And Inflammatory Diseases

: Gut microbiota regulates the host's immune system. Microorganisms and their compounds can co-exist peacefully with the immune system and coordinate its function and regulation. Some microbial clusters may be harmful and others helpful in the respective negative or positive balance of the immune network. These insights have revealed important mechanisms for understanding and treating autoimmune and inflammatory diseases. This Editorial aims to clarify the role of specific genus of gut microbiota, such as Prevotella, in influencing the pathogenesis of Rheumatoid Arthritis (RA).

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Consumption of Dietary Fiber from Different Sources during Pregnancy Alters Sow Gut Microbiota and Improves Performance and Reduces Inflammation in Sows and Piglets

mSystems ◽

10.1128/msystems.00591-20 ◽

2021 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Boshuai Liu ◽

Xiaoyan Zhu ◽

Yalei Cui ◽

Wenjing Wang ◽

Hua Liu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Gut Microbiota ◽

Dietary Fiber ◽

Intestinal Permeability ◽

Systemic Inflammation ◽

Inflammatory Responses ◽

Late Pregnancy ◽

Oxygen Species ◽

Gut Health ◽

Alfalfa Meal

ABSTRACT In pregnant and lactating sows, metabolism and immunity undergo drastic changes, which can lead to constipation, abortion, and intrauterine growth restriction (IUGR) and reduce production performance. Dietary fiber can regulate animal gut microbiota, alleviate inflammatory responses, and improve performance. Here, 48 sows (Large × Landrace) were randomly allocated to groups including, control, and with alfalfa meal (AM), beet pulp, and soybean skin dietary supplementation for 60 days of gestation. The AM diet decreased IUGR, increased food intake during lactation, and promoted the reproductive performance and physical condition of sows. Further, the AM diet significantly reduced markers of intestinal permeability (reactive oxygen species and endotoxin) in sow serum, and of systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor alpha) in sow feces and serum, as well as piglet serum, while it increased the anti-inflammatory marker, IL-10, in sow serum and feces. The AM diet also significantly affected gut microbiota by increasing the relative abundance of proinflammatory bacteria, while decreasing anti-inflammatory bacteria. Moreover, the total short-chain fatty acid (SCFA) content was higher in feces from sows fed an AM diet, with butyric acid content significantly higher during lactation, than in controls. Sow performance was correlated with intestinal permeability, inflammation, and gut microbiota, which were also vertically transmitted to piglets. Our results are significant for guiding feed management in the pig breeding industry. Further, the “sows to piglets” model provides a reference for the effect of dietary fiber on the gastrointestinal function of human mothers and infants. IMPORTANCE Although the direct effects of dietary fiber on gut microbiota composition have been studied extensively, systematic evaluation of different fiber sources on gut health and inflammatory responses of sows and their offspring has rarely been conducted. Excessive reactive oxygen species produced by overactive metabolic processes during late pregnancy and lactation of sows leads to increased endotoxin levels, disordered gut microbiota, decreased SCFA production, and secretion of proinflammatory factors, which in turn causes local inflammation of the gut, potential damage of the gut microbial barrier, increased gut permeability, increased blood endotoxin levels (resulting in systemic inflammation), and ultimately decreased sow and piglet performance. Our results showed that supplementation of the diet with alfalfa meal in mid and late pregnancy can reverse this process. Our findings lay a foundation for improving the gut health of sows and piglets and provide insights into the study of the gastrointestinal tract function in human mothers and infants.

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Gut Microbiota Changes of HIV Patients Before and After One Year of ART

Case Medical Research ◽

10.31525/ct1-nct04297501 ◽

2020 ◽

Author(s):

Keyword(s):

Gut Microbiota ◽

Hiv Patients ◽

Before And After ◽

One Year

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EVALUATION OF THE EFECTS OF ELECTRONIC ACUPUNCTURE COMBINED WITH “TAM TY THANG” REMEDY IN THE TREATMENT OF RHEUMATOID ARTHRITIS BY WIND-COLD-DAMP

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2016.6.17 ◽

2017 ◽

pp. 122-127

Author(s):

Thi Luu Nguyen ◽

Thi Tan Nguyen

Keyword(s):

Rheumatoid Arthritis ◽

Side Effects ◽

Prospective Study ◽

Key Words Rheumatoid Arthritis ◽

Good Effect ◽

Good Level ◽

Relieve Pain ◽

Level Of Activity ◽

Before And After ◽

The Moment

Objectives: To assess the effect of electronic acupuncture combined with “Tam ty thang” remedy in the treatment of rheumatoid arthritis by wind-cold-damp. Materials and methods: prospective study, comparing before and after treatment, including 43 patients who were diagnosed with rheumatoid arthritis by wind-cold-damp according to traditional medicine. Results: good level occupied 69,8%, and fair good level occupied 30,2%.The improved motor function accounted for 95.3%, to relieve pain up to 95,3%, reducing inflammation of VSS in 1 hour at the moment No 31,65, N28 17,88. The improvement in the level of activity of the hand reached 48,8% for good level. Conclusions: The method of electronic acupuncture combined with “Tam ty thang” remedy have a good effect in the treatment of rheumatoid arthritis by wind-cold-damp and it didn’t cause significantly side effects in clinic. Key words: rheumatoid arthritis, electronic acupuncture, “Tam ty thang” remedy

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