Changes in the gut microbiota of mice orally exposed to methylimidazolium ionic liquids

Abstract

Ionic liquids are salts used in a variety of industrial processes, and being relatively non-volatile, are proposed as environmentally-friendly replacements for existing volatile liquids. Methylimidazolium ionic liquids resist complete degradation in the environment, likely because the imidazolium moiety does not exist naturally in biological systems. However, there is limited data available regarding their mammalian effects in vivo. This study aimed to examine the effects of exposing mice separately to 2 different methylimidazolium ionic liquids (BMI and M8OI) through their addition to drinking water. Potential effects on key target organs-the liver and kidney-were examined, as well as the gut microbiome. Adult male mice were exposed to drinking water containing ionic liquids at a concentration of 440 mg/L for 18 weeks prior to examination of tissues, serum, urine and the gut microbiome. Histopathology was performed on tissues and clinical chemistry on serum for biomarkers of hepatic and renal injury. Bacterial DNA was isolated from the gut contents and subjected to targeted 16S rRNA sequencing. Mild hepatic and renal effects were limited to glycogen depletion and mild degenerative changes respectively. No hepatic or renal adverse effects were observed. In contrast, ionic liquid exposure altered gut microbial composition but not overall alpha diversity. Proportional abundance of Lachnospiraceae, Clostridia and Coriobacteriaceae spp. were significantly greater in ionic liquid-exposed mice, as were predicted KEGG functional pathways associated with xenobiotic and amino acid metabolism. Exposure to ionic liquids via drinking water therefore resulted in marked changes in the gut microbiome in mice prior to any overt pathological effects in target organs. Ionic liquids may be an emerging risk to health through their potential effects on the gut microbiome, which is implicated in the causes and/or severity of an array of chronic disease in humans.

Mechanisms of action of ionic liquids on living cells: the state of the art

“…For example: Liver damage, increase in hepatosomatic index, and modified activities of defense enzymes (CAT, GPX, and GST) have been observed in mouse liver exposed to intraperitoneal injection of [C 8 mim][Br] (Yu et al 2008 ). Marked changes in the gut microbiome have been observed in mice exposed to imidazolium-based ILs via drinking water; however, only mild hepatic and renal effects were observed (Young et al 2020 ). As a system biology potential application of ILs, it has been shown that in rats, oral delivery of a choline-based IL prevent the absorption of fat molecules through intestinal tissue, potentially providing a feeling of satiety (Nurunnabi et al 2019 ).…”

“…Marked changes in the gut microbiome have been observed in mice exposed to imidazolium-based ILs via drinking water; however, only mild hepatic and renal effects were observed (Young et al 2020 ).…”

Renal injury and hepatic effects from the methylimidazolium ionic liquid M8OI in mouse

“…Ten hours after administration, the authors report histopathological changes in the liver. More recently, oral exposure to M8OI and a related ionic liquid (both as the Cl-salt) in mice have been shown to modulate the gut microbiota ( Young et al, 2020 ).…”

Active Smoking Induces Aberrations in Digestive Tract Microbiota of Rats

“…Some rodent or human-based studies have confirmed that smoking could result in alterations in community structure and taxonomic abundances in a certain segment of the digestive tract ( Vogtmann et al., 2015 ; Lee et al., 2018 ; Shanahan et al., 2018 ; Al-Zyoud et al., 2019 ; Sublette et al., 2020 ; Tam et al., 2020 ; Young et al., 2020 ; Prakash et al., 2021 ). Our results further confirmed that active smoking could induce a comprehensive effect on community structures and taxonomic abundances in the whole digestive tract.…”