The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility

  • Ravichandra Vemuri
  • Kristyn E. Sylvia
  • Sabra L. Klein
  • Samuel C. Forster
  • Magdalena Plebanski
  • Raj Eri
  • Katie L. Flanagan


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.


Adaptive immunity Innate immunity Sex differences Sex hormones Probiotics Faecal microbiota transplant Bacteriotherapy 



dendritic cell



intestinal epithelial cells



We would like to acknowledge Claudio Rosa for designing the figure.


KES was supported by the NIH/NIAID Center of Excellence in Influenza Research and Surveillance contracts HHS N272201400007C; SCF is supported by NHMRC CJ Martin Fellowship (1091097) and the Victorian Government’s Operational Infrastructure Support Program; MP is supported by a NHMRC Senior Research Fellowship. RE and KLF are recipients of a grant from the Clifford Craig Foundation for microbiota research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Health Sciences, College of Health and MedicineUniversity of TasmaniaHobartAustralia
  2. 2.The W. Harry Feinstone Department of Molecular Microbiology and ImmunologyThe Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  3. 3.Microbiota and Systems Biology Laboratory, Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchMelbourneAustralia
  4. 4.Department of Molecular and Translational SciencesMonash UniversityMelbourneAustralia
  5. 5.School of Health and Biomedical ScienceRMIT UniversityMelbourneAustralia
  6. 6.Department of Immunology and PathologyMonash UniversityMelbourneAustralia

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