How and Why Men and Women Differ in Their Microbiomes: Medical Ecology and Network Analyses of the Microgenderome

Abstract Microgenderome or sexual dimorphism in microbiome refers to the bidirectional interactions between microbiotas, sex hormones, and immune systems, and it is highly relevant to disease susceptibility. A critical step in exploring microgenderome is to dissect the sex differences in key community ecology properties, which has not been systematically analyzed. This study aims at filling the gap by reanalyzing the Human Microbiome Project datasets with two objectives: (i) dissecting the sex differences in community diversity and their intersubject scaling, species composition, core/periphery species, and high‐salience skeletons (species interactions); (ii) offering mechanistic interpretations for (i). Conceptually, the Vellend–Hanson synthesis of community ecology that stipulates selection, drift, speciation, and dispersal as the four processes driving community dynamics is followed. Methodologically, seven approaches reflecting the state‐of‐the‐art research in medical ecology of human microbiomes are harnessed to achieve the objectives. It is postulated that the revealed microgenderome characteristics (categorized as seven aspects of differences/similarities) exert far reaching influences on disease susceptibility, and are primarily due to the sex difference in selection effects (deterministic fitness differences in microbial species and/or species interactions with each other or with their hosts), which are, in turn, shaped/modulated by host physiology (immunity, hormones, gut–brain communications, etc.).