Sunset Yellow dye effects on gut microbiota, intestinal integrity, and the induction of inflammasomopathy with pyroptotic signaling in male Wistar rats

Abstract

Although concern persists regarding possible adverse effects of consumption of synthetic azo food dyes, the mechanisms of any such effects remain unclear. We have tested the hypothesis that chronic consumption of the food dye Sunset Yellow (SY) perturbs the composition of the gut microbiota and alters gut integrity. Male rats were administered SY orally for 12 weeks. Analysis of fecal samples before and after dye administration demonstrated SY-induced microbiome dysbiosis. SY treatment reduced the abundance of beneficial taxa such as Treponema 2, Anaerobiospirillum, Helicobacter, Rikenellaceae RC9 gut group, and Prevotellaceae UCG-003, while increasing the abundance of the potentially pathogenic microorganisms Prevotella 2 and Oribacterium. Dysbiosis disrupted gut integrity, altering the jejunal adherens junction complex E-cadherin/β-catenin and decreasing Trefoil Factor (TFF)-3. SY administration elevated LPS serum levels, activated the inflammatory inflammasome cascade TLR4/NLRP3/ASC/cleaved-activated caspase-1 to mature IL-1β and IL-18, and activated caspase-11 and gasdermin-N, indicating pyroptosis and increased intestinal permeability. The possibility that consumption of SY by humans could have effects similar to those that we have observed in rats should be examined.

Keywords: Azo dyes; E-Cadherin/β-catenin; Inflammasome; Sunset yellow; TFF-3; Toxicomicrobiomics.