An osmotic laxative renders mice susceptible to prolonged Clostridioides difficile colonization and hinders clearance

Abstract

Antibiotics are a major risk factor for Clostridioides difficile infections (CDIs) because of their impact on the microbiota. However, non-antibiotic medications such as the ubiquitous osmotic laxative polyethylene glycol (PEG) 3350 also alter the microbiota. Clinicians also hypothesize that PEG helps clear C. difficile. But whether PEG impacts CDI susceptibility and clearance is unclear. To examine how PEG impacts susceptibility, we treated C57Bl/6 mice with 5-day and 1-day doses of 15% PEG in the drinking water and then challenged the mice with C. difficile 630. We used clindamycin-treated mice as a control because they consistently clear C. difficile within 10 days post-challenge. PEG treatment alone was sufficient to render mice susceptible and 5-day PEG-treated mice remained colonized for up to 30 days post-challenge. In contrast, 1-day PEG treated mice were transiently colonized, clearing C. difficile within 7 days post-challenge. To examine how PEG treatment impacts clearance, we administered a 1-day PEG treatment to clindamycin-treated, C. difficile-challenged mice. Administering PEG to mice after C. difficile challenge prolonged colonization up to 30 days post-challenge. When we trained a random forest model with community data from 5 days post-challenge, we were able to predict which mice would exhibit prolonged colonization (AUROC = 0.90). Examining the dynamics of these bacterial populations during the post-challenge period revealed patterns in the relative abundances of Bacteroides, Enterobacteriaceae, Porphyromonadaceae, Lachnospiraceae, and Akkermansia that were associated with prolonged C. difficile colonization in PEG-treated mice. Thus, the osmotic laxative, PEG, rendered mice susceptible to C. difficile colonization and hindered clearance.

Single-strain behavior predicts responses to environmental pH and osmolality in the gut microbiota

“…Having shown the in vitro generalizability of pH and osmolality resilience in a complex microbiota for several key taxa, we explored whether these phenotypes would also be consistent in vivo , where, beyond microbiota interactions, the interplay with host dynamics plays a significant role in determining bacterial abundance. As other studies have investigated the response to osmolality in vivo (14, 43), we sought to investigate how the microbiota is affected by changes in pH in vivo . We reasoned that changing diet would impact gut pH differentially in the various intestinal compartments (43).…”

“…As other studies have investigated the response to osmolality in vivo (14, 43), we sought to investigate how the microbiota is affected by changes in pH in vivo . We reasoned that changing diet would impact gut pH differentially in the various intestinal compartments (43). Specifically, microbial fermentation of carbohydrates in the cecum and colon produces SCFAs, lowering the pH of these intestinal compartments.…”