Dietary emulsifier polysorbate‐80‐induced small‐intestinal vulnerability to indomethacin‐induced lesions via dysbiosis

Abstract

Background and AimDietary emulsifiers are widely used in processed foods and officially approved as safe for intake. However, recent studies have demonstrated that some emulsifiers alter the colonic microbiota, leading to colonic low‐grade inflammation, in mice. The effect of dietary emulsifiers on small‐intestinal microbiota, which is important for gut immunity, has not been studied. We aimed to investigate the effect of a representative dietary emulsifier, polysorbate‐80 (P80), on the small‐intestinal microbiota in normal mice.MethodsSome mice were pretreated with P80 for 8 weeks with or without indomethacin administration on the last 2 days, and intestinal damage was evaluated histologically. The ileal and colonic microbiota composition was assessed using 16S rRNA polymerase chain reaction.ResultsPolysorbate‐80 increased the Gammaproteobacteria abundance and decreased the α‐diversity in the small intestine. No decrease in α‐diversity was observed in the colon. P80 pretreatment exacerbated the indomethacin‐induced small‐intestinal lesions and significantly increased the interleukin‐1β expression. Culture of ileal content on deoxycholate hydrogen sulfide lactose agar showed that P80 significantly increased the colonies of the sulfide‐producing bacteria Proteus spp. (genetically identified as Proteus mirabilis). Antibiotic pretreatment abolished the P80‐induced aggravation of indomethacin‐induced ileitis. Motility assay in semisolid agar showed that adding 0.02% P80 to the agar significantly increased the diameter of P. mirabilis colonies but not that of Escherichia coli colonies.ConclusionsPolysorbate‐80 enhances the vulnerability of the small intestine to indomethacin‐induced injury by inducing ileal dysbiosis. Direct enhancement of the motility of specific flagellated microbiota by P80 might be related to dysbiosis and intestinal injury.

Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood

“…B. Chassaing et al demonstrated that mice treated with 1% P80 dissolved in drinking water for 12 weeks had low-grade inflammation, obesity/metabolic syndrome, and colitis ( 5 ). Moreover, H. Furuhashi et al also found 1% P80 could induce small intestine vulnerability to indomethacin-induced lesions ( 54 ). Thus, we also chose 1% P80 as the intervention concentration.…”

“…Mice from the P80 group were exposed to P80 dissolved in sterilized water (1.0% [wt/vol]), whereas the control water group was supplied with sterilized water without P80. The dose was chosen based on a previous study ( 5 , 54 ). Female mice in the two groups were mated with male mice after 3 weeks of predisposing with sterilized water or P80 dissolved in sterilized water and checked daily.…”

NSAID–Gut Microbiota Interactions

“…High fat diet aggravates indomethacin-induced small intestinal damage in mice via intestinal dysbiosis, increases gene expression of interleukin (IL)-17A in the intestine and augments intestinal permeability ( Sugimura et al., 2019 ). A dietary emulsifier, polysorbate 80, exacerbates indomethacin-induced small-intestinal lesions via intestinal dysbiosis and increases protein expression of IL-1 β in the small intestine ( Furuhashi et al., 2019 ). A possible mechanism by which indomethacin can cause the translocation of luminal bacteria from the lumen into the mucosa is by altering the content of sugars and lipids in the glycocalyx layer of the mucosa ( Basivireddy et al., 2005 ).…”

Food additives: Assessing the impact of exposure to permitted emulsifiers on bowel and metabolic health – introducing the FADiets study

“…Secondary endpoints of the FADiets study include changes in bacterial diversity and metabolic activity, gut inflammation and glucose metabolism. Alterations to the composition of the gut microbiota have been observed in animal models following exposure to emulsifiers (Table ), with some reporting increased Proteobacteria (Chassaing et al ; Furuhashi et al ). We will monitor for any differences in faecal bacterial community structure between habitual diet, and the high‐ and low‐emulsifier diets by Illumina MiSeq sequencing of the V1–V2 regions of bacterial 16S rRNA genes isolated from participant faecal samples.…”