Introduction The human gut microbiome comprises trillions of microorganisms that shape digestion, immunity, metabolism, and behavior. Increasingly, research shows that male and female gut ecosystems differ in composition, functionality, and disease associations. Understanding these differences matters for research and personalized health strategies. Sex as a Biological Variable Sex hormones, immune differences, and lifelong behavioral patterns create distinct ecological niches in male and female guts. The NIH’s emphasis on sex as a biological variable (SABV) reflects growing evidence that failing to account for sex can obscure important findings in autoimmunity, metabolic disease, mental health, and drug response. Key compositional patterns Several cross-sectional and longitudinal studies identify reproducible trends. Males often exhibit higher relative abundances of Bacteroides, Alistipes, and Ruminococcus, while females more commonly show enrichment of Bifidobacterium, Lactobacillus, and Prevotella. Alpha diversity (within-individual richness) differences are inconsistent across cohorts, with some reports of slightly higher diversity in men. Women can show greater interpersonal beta diversity, suggesting more variability between individuals. Hormonal and immune drivers Estrogens, progesterone, and testosterone influence microbial selection and activity. Estrogen tends to promote Lactobacillus growth and enhance gut barrier integrity; it also interacts with the estrobolome — bacterial enzymes that metabolize estrogens and modulate circulating hormone levels. Testosterone has been associated with altered Bacteroides abundance and shifts in microbial metabolite profiles, including short-chain fatty acids. Immune system differences also play a role: females generally mount stronger innate and adaptive responses, which can shape colonization resistance and microbial resilience. Diet, behavior, and lifecycle effects Dietary patterns and lifestyle choices compound biological effects. Men on average consume more red meat and alcohol, which favors Bacteroides-dominant communities and can reduce SCFA-producing taxa. Women’s greater intake of fruits, vegetables, and fermented foods tends to support Bifidobacterium and Lactobacillus. Microbial differences begin at birth, evolve through puberty with hormonal surges, stabilize in adulthood, and shift again during menopause or andropause alongside hormonal decline. Clinical implications Sex-specific microbiome patterns help explain differing disease risks. Autoimmune disorders are more prevalent in women and may reflect more intense microbiota–immune interactions. Men have higher population-level risk for metabolic syndrome and NAFLD, possibly linked to distinct microbial metabolite profiles. The gut–brain axis also exhibits sex-based signaling differences relevant to anxiety and depression. Functional nodes: estrobolome and androgen-modulating bacteria The estrobolome regulates estrogen reactivation and clearance, affecting processes from menopausal symptoms to hormone-sensitive cancer risk. Certain microbes can modify androgens or produce androgen-like compounds, potentially influencing muscle, mood, and libido. Research horizons Priority areas include sex-specific probiotic and dietary strategies, microbiome effects in transgender health and hormone therapy, and diagnostics that integrate sex as a core variable. Integrative models that couple microbiome, hormonal, immune, and lifestyle data will be essential for robust, generalizable conclusions. For an extended discussion of sex-based microbiome differences, see [How Male and Female Gut Microbiomes Differ: A Scientific Deep Dive](https://www.innerbuddies.com/blogs/gut-health/male-vs-female-gut-microbiome-differences). Related reading on probiotic needs and broader microbiome context is available at How your unique microbiome dictates your probiotic needs and Gut microbiome: the good, the bad, and the ugly. For reference resources or testing options, see microbiome test. Final thoughts Male and female gut microbiomes reflect an interplay of hormones, immunity, diet, and life stage. Recognizing sex-specific patterns improves interpretation of microbiome studies and supports more precise research and clinical approaches.