| 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. |