Combined administration of fructooligosaccharides and Clostridium butyricum attenuates bowel cleansing-induced dysbiosis and safeguards mucosal defense in a murine model.

Bowel preparation with polyethylene glycol electrolyte solution is indispensable for gastrointestinal endoscopy and related procedures. However, it disrupts gut microbial homeostasis and increases host vulnerability to ensuing infection. In a murine model, we optimized a synbiotic intervention consisting of fructooligosaccharides (FOS) and Clostridium butyricum (C. butyricum) to improve post-cleansing microbiome resilience and mucosal defense. We evaluated its efficacy and longitudinally monitored the dynamics of gut microbiota in response to bowel cleaning and concurrent bacterial challenge infection. Our data show that the bowel preparation induced a persistent microbial perturbation, resulting in an incomplete spontaneous recovery 15 days after the procedure. A 12-day symbiotic intervention significantly enriched alpha diversity and restored the dysbiosis induced by the cleaning. The intervention also increased the Firmicutes/Bacteroidota ratio and the abundance of several key beneficial bacteria in the genera Lactobacillus, Mucispirillum, and Butyricicoccus. Under infectious stress, bowel cleansing markedly aggravated colitis phenotypes, while the intervention alleviated crypt hyperplasia and attenuated inflammatory injury in mice infected with Citrobacter rodentium, resulting in a significant improvement in several colitis indicators. The synbiotic was accompanied by enhanced IL-12/IFN-γ-related antimicrobial responses, increased expression of Muc2 and sIgA, and reshaped bacterial interaction networks disrupted by challenge infection. Our findings demonstrate that the combined administration of FOS and C. butyricum promotes gut microbial homeostasis and host defense. This approach may provide insights into potential dietary strategies for mitigating bowel cleansing-induced microbial disturbances.