Polyethylene Glycol 3350 Changes Stool Consistency and the Microbiome but not Behavior of CD1 Mice

Abstract

Objectives: Polyethylene Glycol 3350 (PEG3350) is a laxative commonly used to treat constipation in children. The Food and Drug Administration has received reports of increased anxiety, aggression, and obsessive-compulsive behaviors in children administered PEG3350. Thus, we assessed whether daily administration of PEG3350 leads to anxiety-like behavior in mice. Methods: Outbred CD-1 IGS mice were administered either a high or a low dose of PEG3350 via daily oral gavage for 2 weeks. As a laxative comparison and control, additional mice were given a high or low dose of magnesium citrate or vehicle (water). Weight and stool consistency were assessed after each gavage to determine laxative effectiveness. Anxiety-like behaviors were assessed using light/dark, open field, and elevated plus maze (EPM) tests at baseline, after 2 weeks of daily gavage, and after a 2 week washout in experiment 1, and after 2 weeks of daily gavage in experiment 2. Stool samples were collected for microbiome analysis in experiment 2 at baseline, after 2 weeks of daily gavage, and after 2 weeks washout. Results: PEG3350 and magnesium citrate significantly changed stool consistency, as well as microbiome alpha and beta diversity. Anxietylike behaviors were not, however, different in mice administered low or high doses of PEG3350 or magnesium citrate. Conclusions: Although changes in stool consistency and the gut microbiome occurred, administration of PEG3350 did not alter anxiety-like behaviors.

Laxative abuse is associated with a depleted gut microbial community structure among females and males with binge-eating disorder or bulimia nervosa: The Binge Eating Genetics Initiative (BEGIN)

“…The lower microbial diversity we observed among participants who reported laxative use is consistent with the effect of polyethylene glycol (PEG; an osmotic laxative) on the murine microbiota (69,70). PEG treatment also induced sustained alterations in the intestinal microbial composition of these mice, via disruption of the mucus barrier, an altered immune response, and increased osmolality (69).…”

An Update of Pharmacological Management in Children with Functional Constipation

“…However, to date, evidence on any relationship between PEG and neuropsychiatric events remains limited to anecdotal reports [36]. In addition, several studies have demonstrated that the administration of PEG does not lead to elevated blood levels of neurotoxins in children and does not lead to anxiety-like behavior in mice [38][39][40]. The Food and Drug Administration is currently still investigating the long-term safety of PEG in children, but has stated that no changes in current policy are necessary.…”

Raising the Bar on Translational Studies to Test the Neurobehavioral Effects of Laxatives

“…In this issue, Salman et al (9) take a translational approach to this problem, testing the behavioral effects of administering PEG 3350 once daily for 14 days to young adult, outbred CD‐1 mice. They found no difference in three different measures of anxiety‐like behaviors in mice that received low dose or high dose PEG 3350 when compared to mice treated with a different laxative (magnesium citrate) or vehicle.…”