Sex differences in immunity are well described in the literature and thought to 
be mainly driven by sex hormones and sex-linked immune response genes. The 
gastrointestinal tract (GIT) is one of the largest immune organs in the body and 
contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's 
patches and elsewhere, which together have profound effects on local and 
systemic inflammation. The GIT is colonised with microbial communities composed 
of bacteria, fungi and viruses, collectively known as the GIT microbiota. The 
GIT microbiota drives multiple interactions locally with immune cells that 
regulate the homeostatic environment and systemically in diverse tissues. It is 
becoming evident that the microbiota differs between the sexes, both in animal 
models and in humans, and these sex differences often lead to sex-dependent 
changes in local GIT inflammation, systemic immunity and susceptibility to a 
range of inflammatory diseases. The sexually dimorphic microbiome has been 
termed the 'microgenderome'. Herein, we review the evidence for the 
microgenderome and contemplate the role it plays in driving sex differences in 
immunity and disease susceptibility. We further consider the impact that 
biological sex might play in the response to treatments aimed at manipulating 
the GIT microbiota, such as prebiotics, live biotherapeutics, (probiotics, 
synbiotics and bacteriotherapies) and faecal microbial transplant. These 
alternative therapies hold potential in the treatment of both psychological 
(e.g., anxiety, depression) and physiological (e.g., irritable bowel disease) 
disorders differentially affecting males and females.