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 200mg/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 ~2000 kcal/d SED. Multi-omic 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 effects of SED indicating a limited but potentially important interplay between androgen status and the gut microbiota under conditions of SED.