Testosterone administration partially modulates gut microbiota responses to severe energy deficit

Severe diet- and exercise-induced energy deficit (SED) suppresses androgen production in healthy men, altering metabolism and driving muscle loss. The gut microbiota modulates host metabolism, yet the community's response to SED and any role of androgen hormones are unclear. Herein, healthy, physically active men were randomized to receive 200 mg/wk testosterone enanthate (n = 24) or placebo (n = 26) during a 28-day residential intervention that restricted energy intake and increased energy expenditure inducing a ∼2,000 kcal/day SED. Multiomic analyses revealed altered gut microbiota composition, reduced fecal short-chain fatty acids (SCFA), and shifts in bacterial metabolic pathways toward lipid utilization and mucin degradation during SED, suggesting adverse effects of SED on gut microbiota metabolic functions. Testosterone administration preserved certain SCFA-producing taxa and bioenergetic pathways without fully counteracting the effects of SED indicating a limited but potentially important interplay between androgen status and the gut microbiota under conditions of SED.NEW & NOTEWORTHY This study is the first to demonstrate that testosterone administration partially preserves gut microbiota composition and metabolic function during severe energy deficit in healthy men. Using a multiomic approach, we show that testosterone modulates short-chain fatty acid-producing taxa and microbial pathways linked to host energy metabolism. These findings reveal a novel role for androgens in shaping host-microbiome interactions during catabolic stress and may inform strategies to maintain metabolic resilience.