Liraglutide Modifies Gut Microbiota Without Modulating Doxorubicin-Induced Toxicity in Rats

Doxorubicin is an effective chemotherapeutic agent, but it causes gastrointestinal toxicity that impairs treatment efficacy and quality of life. This study investigated the effects of liraglutide, a GLP-1 analog, on acute doxorubicin-induced gut toxicity in rats. Sixty male Wistar rats were assigned to four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). Groups L and DL received liraglutide (0.6 mg/kg, s.c.) for two weeks. D and DL were given a single dose of doxorubicin (20 mg/kg, i.p). After 48 h, the distal colon, feces, and blood were collected. Results: Doxorubicin caused crypt disruption, goblet cell loss, apoptosis, and reduced fecal short-chain fatty acids. Levels of TNF-α, NF-κB, Bcl-2, TLR4, and antioxidant enzymes were unchanged among groups. Microbiota analysis showed similar α-diversity but altered β-diversity. Doxorubicin reduced Bacteroidetes and increased Proteobacteria, with higher Arcanobacterium and Clavibacter genera abundance. Liraglutide alone decreased Bacteroidetes and increased Corynebacterium and Actinobaculum genera. Combined treatment showed no significant effects. We conclude that acute doxorubicin administration induces intestinal structural damage, reduces short-chain fatty acids, and changes microbiota composition. Although liraglutide alters microbial profiles, it does not attenuate doxorubicin-induced gut toxicity.