Distinct Effects of GnRH Immunocastration Versus Surgical Castration on Gut Microbiota

Surgical castration, a common practice in animal husbandry, raises animal welfare concerns and adversely affects growth performance. Active immunization against gonadotropin-releasing hormone (GnRH) provides a non-surgical alternative. Both methods ultimately suppress sex hormone production, but their comparative effects on the gut microbiota, a crucial regulator of host health and metabolism, remain unclear. Here, 60 Sprague Dawley (SD) rats were randomly allocated into three groups-control (<i>n</i> = 20; 10 female and 10 male), surgical castration (<i>n</i> = 20; 10 female and 10 male), and GnRH immunocastration groups (<i>n</i> = 20; 10 female and 10 male)-at 4-5 weeks of age to comparatively investigate the impacts of surgical versus GnRH immunocastration on the gut microbiota. Our study demonstrated GnRH immunocastration significantly reduced gonadal weight, effectively suppressing gonadal development to a level comparable to surgical castration. However, the two methods induced distinct, sex-dependent shifts in the gut microbiota. Surgical castration reduced the gut microbial community diversity, whereas the community structure of GnRH immunocastrated rats more closely resembled that of the control group, indicating a milder impact on the microbial diversity and composition. Notably, GnRH immunocastration resulted in higher microbial alpha diversity than surgical castration in both female and male SD rats. Specific bacterial genera, such as <i>Clostridia</i>_UCG014, <i>Lactobacillus</i>, and <i>Lachnospiraceae</i>_UCG006, were similarly altered in both surgical castration and GnRH immunocastration female SD rats, while <i>Intestinimonas</i> and <i>Erysipelatoclostridiaceae</i>_UCG004 were concurrently changed in male SD rats. Conversely, <i>Eubacterium_nodatum</i>_group exhibited opposite responses, increasing with GnRH immunocastration but decreasing with surgical castration in male SD rats. Functional prediction revealed fundamental sex differences in microbial metabolic pathways. In females, nitrogen metabolism, glyoxylate/dicarboxylate metabolism, and mismatch repair were changed, while the pathways involved in siderophore biosynthesis, the citrate cycle (TCA cycle), genetic information processing, and amino acid metabolism were changed in male SD rats. In conclusion, GnRH immunocastration appears to be a less disruptive intervention, better preserving microbial diversity and inducing a unique functional profile. These findings highlighted the importance of considering the castration method's impact on the gut microbial ecosystem in animal production and provided insights for developing humane and effective approaches to animal population control.