In a paper recently published in Advanced Science, Prof. Sam MA and Ms. Wendy LI from Kunming Institute of Zoology (KIZ) of the Chinese Academy of Sciences presented seven aspects of the sex differences in the human microbiomes at 15 body sites, including oral, gut, skin and airway.  

Formally, the sex differences or sexual dimorphism in the human microbiomes are referred to as microgenderome, a term coined by M. B. Flak in commenting a study by JG Markle et al on the relationship between susceptibility to diabetes and gut microbiome with the mouse model. This study provides references or baselines for further investigating the relationships between human microbiomes and disease susceptibilities, particularly autoimmune diseases, such as type-I diabetes. 

For example, type-I diabetes is about twice as common in women as it is in men, but gout is significantly more common in men than in women. The researchers have discovered numerous similar cases in other diseases including neurodegenerative diseases and certain cancers. It is widely believed that human microbiomes may play a critical role for the disease-susceptibility differences through their interactions with hormones and immune systems, or the gut-microbiome-brain communications.   

Microgenderome or sexual dimorphism in the human 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 before MA and LI’s study. Their study filled the gap by reanalyzing the human microbiome project (HMP) datasets with two objectives.

Firstly, the study dissected the sex differences in community diversity and their inter-subject scaling, species composition, core/periphery species and high-salience skeletons (species interactions) in the microbiome networks. Secondly, it offered mechanistic interpretations for the sexual dimorphism or microgenderome.

Methodologically, seven approaches reflecting the state-of-the-art research in medical ecology of human microbiomes are harnessed to achieve their objectives. Most analytic approaches used were developed by Prof. MA’s lab (Computational Biology and Medical Ecology Lab of KIZ) over the past few years.   

The researchers postulated that the discovered 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 evolutionary 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).  

How and why men and women differ in their microbiome based on the medical ecology and network analyses. (Image by Sam MA and Wendy LI)