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Sex has been universally acknowledged as a confounding factor in every type of biological study, while there are strong sex differences in morbidity along the lifespan. Humans have almost identical genomes (99.2%), yet minor variance in their DNA produces remarkable phenotypic diversity across the human population. On the other hand, metagenomic analysis of the human microbiome is more variable, depending on the sex, lifestyle, geography, and age of individuals under study. Immune responses in humans also exhibit variations, with an especially striking sexual dimorphism, which is at play in several other physiologic processes. Sex steroids have noticeable effects on the composition of the human microbiome along the lifespan, accompanied by parallel changes in immunity and the stress response. Gut microsex/genderome, a recently coined term, defines the sexually dimorphic gut microbiome. Apart from the sex steroids, the stress hormones are also at play in the proliferation of microbes. This review summarizes the concept of gut microsex/genderome under the prism of recent studies on the interrelations of the sexually dimorphic microbiome with immunity and stress.