# Commercially purchased and in-house bred C57BL/6 mice with different gut microbiota exhibit distinct indomethacin-induced toxicities

## TL;DR

Mice from different sources have different gut microbes, which affect how they respond to the drug indomethacin, causing varying levels of intestinal damage.

## Contribution

This study shows that mouse vendor differences in gut microbiota significantly influence NSAID-induced intestinal toxicity.

## Key findings

- Tar Heel mice showed greater indomethacin toxicity compared to Charles River mice.
- Tar Heel mice had higher levels of β-glucuronidase-producing and mucolytic bacteria.
- Gut microbiome differences may explain the varied NSAID responses between mouse vendors.

## Abstract

Nonsteroidal anti-inflammatory drug (NSAID)-induced toxicities are a significant clinical problem, yet the factors influencing these outcomes remain incompletely understood. Here, we investigated the impact of a mouse vendor on indomethacin-induced injury using C57BL/6 mice from different breeding facilities (in-house ‘Tar Heel’ and commercial Charles River). We found that Tar Heel mice exhibited significantly greater susceptibility to indomethacin toxicity, characterized by greater body weight loss, increased ileal ulceration, elevated fecal lipocalin-2 levels, and higher goblet cell numbers in the ileum compared to Charles River mice. Importantly, whole-genome metagenomic analysis revealed distinct baseline gut microbiomes between the two types of mice. Notably, Tar Heel mice presented increased abundances of β-glucuronidase (GUS)-producing bacteria, particularly those expressing Loop−1 GUS enzymes, and elevated levels of mucolytic enzyme-encoding bacteria. These differences suggest that the increased indomethacin toxicity observed in Tar Heel mice may be related to functional changes in their gut microbiome, which may predispose them to an exaggerated response to NSAID exposure. Together, our findings demonstrate that vendor-specific differences significantly influence NSAID-induced intestinal toxicity and highlight the importance of considering mouse sources and gut microbial compositions in experimental design. Moreover, we highlight the potential functional roles that gut microbes play in host–indomethacin interactions.