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

Schematics of proposed pathway for inhibitory connection between butyrate and pyroptosis cell death. Danger signals in diabetic patients detected by Toll-like receptors (TLRs). This initiates a signalling cascade that leads to cell death by pyroptosis or caspase-1-dependent cell death (through activation of nuclear factor-κB (NF-κB), stimulation of inflammasomes and production of inflammatory cytokines including IL-1β and IL-18). Butyrate can modulate the immune response and alleviate pyroptosis cell death via upregulation of miR-146a and miR-9. ▪ : increased level ▪ : inhibition. [Display omitted] •Diabetes prevalence has been rising more rapidly worldwide.•Pyroptosis is characterized by release of pro-inflammatory mediators and cytokines.•Some food ingredients may modulate inflammatory pathways via molecular mechanisms.•Sodium butyrate may exert beneficial actions for attenuating inflammation.•The prebiotic inulin alleviates inflammation via fermentation to butyrate. 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). 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/). Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1β & IL-18 were significantly downregulated (p