Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial

Roshanravan, N. and Alamdari, N.M. and Jafarabadi, M.A. and Mohammadi, A. and Shabestari, B.R. and Nasirzadeh, N. and Asghari, S. and Mansoori, B. and Akbarzadeh, M. and Ghavami, A. and Ghaffari, S. and Ostadrahimi, A. (2020) Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Cytokine, 131.

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Purpose: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). Methods: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). Results: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1β & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. Conclusion: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link. © 2020

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: butyric acid; catalase; cryopyrin; immunoglobulin enhancer binding protein; immunoglobulin enhancer binding protein 1; interleukin 18; interleukin 1beta; interleukin 1beta converting enzyme; inulin; messenger RNA; microRNA 146a; microRNA 9; placebo; superoxide dismutase; toll like receptor 2; toll like receptor 4; unclassified drug, adult; antioxidant activity; Article; body mass; cohort analysis; controlled study; double blind procedure; down regulation; enzyme linked immunosorbent assay; female; human; major clinical study; male; non insulin dependent diabetes mellitus; peripheral blood mononuclear cell; population research; priority journal; protein expression; protein RNA binding; protein targeting; pyroptosis; questionnaire; randomized controlled trial; real time polymerase chain reaction
Subjects: WK Endocrine System
Depositing User: eprints admin
Date Deposited: 20 Sep 2020 07:31
Last Modified: 20 Sep 2020 07:31
URI: http://eprints.iums.ac.ir/id/eprint/23358

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