Stage-specific gut microbial restructuring drives estrous transition in rabbits

This study aimed to investigate the relationship between colonic microbiota and estrous cycle transition in rabbits by integrating 16S rRNA gene sequencing and metabolomic analyses to identify key microbial taxa and metabolites involved in estrus regulation.

Sixteen female New Zealand white rabbits were divided into diestrus and early estrus groups based on vulvar mucosa color and serum estradiol (E2) concentration. Colonic microbiota dynamics were assessed via 16S rRNA sequencing, while metabolomes of colonic contents were profiled using ultra-high performance liquid chromatography-tandem mass spectrometry. Fecal microbiota transplantation (FMT) was performed by oral administration of colonic contents from diestrus or early estrus rabbits to mice with disrupted estrous cycles to evaluate the regulatory effects of microbiota. Exogenous indole- 3-acetic acid (IAA) was administered to both mice and rabbits to assess its role in estrus onset and cyclicity restoration.

Colonic microbial composition differed significantly between diestrus and early estrus rabbits. The genera Anaerostipes and Ruminiclostridium were enriched in early estrus, while the genera Oscillospirales UCG_010 and UCG_005 were more abundant in diestrus. FMT from early estrus donors restored cyclicity in mice with disrupted cycles, whereas diestrus FMT did not. Metabolomics identified IAA as a key elevated metabolite in early estrus, and this metabolite accelerated estrus onset and restored cyclicity in both mice and rabbits.

These findings demonstrate that gut microbiota restructuring regulates the estrous transition in rabbits, providing a basis for developing microbiota-targeted strategies to enhance reproductive efficiency in rabbit production and optimize animal reproductive management.