Male castration increases adiposity via small intestinal microbial alterations

Castration of young males is widely used in the cattle industry to improve meat quality, but the mechanism linking hypogonadism and host metabolism is not clear. Here, we use metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. After pubescence, the CtM cattle harbor distinct ileal microbiota dominated by the family Peptostreptococcaceae and exhibit distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. We also evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. Castration of male mice phenocopies both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model confirm that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals. Collectively, targeting the gut microbiota is a potential therapeutic strategy for the treatment of both hypogonadism and obesity. Synopsis Primary hypogonadism caused in cattle and mouse by male castration leads to alterations of the ileal microbiota. These changes induce aberrant systemic, muscular and intestinal metabolome profiles, resulting in increased fat storage. Male castration alters the gut microbial profile, with a marked increase in the ileal abundance of Peptostreptococcaceae . Hypogonadal animals have distinct metabolomic signatures, characterized by high levels of branched-chain amino acids. Obese phenotypes linked to hypogonadism are transferrable by fecal microbiota transplantation to a eugonadal recipient. Graphical Abstract Primary hypogonadism caused in cattle and mouse by male castration leads to alterations of the ileal microbiota. These changes induce aberrant systemic, muscular and intestinal metabolome profiles, resulting in increased fat storage.