Enter the microgenderome

By Julia Wiebe, Ph.D., MBA & Susan Hewlings, Ph.D., R.D.

With the rising awareness of mental health as a growing concern in our world today, it is evident that some conditions have a different impact and expression across gender lines. Notably, women have about twice the lifetime rate of depression and anxiety when compared to men. Science is still catching up to all the complex reasons for this disparity – which may include factors ranging from genetics to environment.  

 “The differences in gender run far deeper than anatomy,” states David Foreman, The Herbal Pharmacist. “The need for studies specifically designed for a particular gender are imperative. The differences in metabolism, hormones, body structure and size are just a few of the contributing factors driving the need for gender-specific research. To achieve the proper outcome for everyone, we need to make sure we are addressing all the possible angles for which gender may be the largest differentiator.” 

The need for more gender-specific studies 

Interestingly, while there are more female participants in many mental health studies, unique studies of women (and of men) are lacking. 

Previous studies have shown that gender differences play a substantial role in the influence of mental disorders. For example, in the context of Social Anxiety Disorder (SAD), the prevalence is nearly twice as high in women compared to men. While women report greater clinical severity, men with the disorder may seek treatment to a greater extent. The reason for this difference is still being debated.  

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Understanding gender differences in a condition like SAD is key for both diagnosis and treatment. If we can conduct unique studies of women, this will help guide gender-sensitive and specifically-tailored interventions, which is key to improving outcomes. The impact of this could be far-reaching.  

“SAD impairs professional life especially for those in roles that require regular public speaking, conversations with strangers, talking in meetings or in groups, starting conversations and talking to authority figures,” said Monica Olivares Martín, R&D director for women and infant nutrition at Kerry. “Thus, this condition limits opportunities for women to progress in their careers and take leadership positions. Studies show gender differences also have an impact on a professional level. For example, compared to men with SAD, fewer women with the disorder are employed and among those employed, men are more likely to be employed on a full-time basis compared to women.” 

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The ‘microgenderome’ 

While we often think of the role of the microbiome in gut health, immunity and metabolism, its role in mental health is getting more attention.  

Part of the explanation for why men and women experience conditions like SAD so differently may be related to the gender-specific differences in the male and female gut microbiota composition that influences mood and feelings of anxiety via the gut-brain axis. Research indicates that gender differences in the gut-brain axis may contribute to the discrepancies in incidence of neuropsychiatric disorders between females and males.  

Animal studies have provided some of the most pertinent information on sex differences in stress and anxiety to date. For example, one study reported that some of the increased risk of anxiety and depression associated with being female might partially be due to the remodeling of the gut microbial community and subsequent immune alterations that accompany hormonal changes associated with pregnancy, postpartum health and menopause. 

“In this gut-brain axis there is a third player, estrogen, a steroid-derived sex hormone that drives not only reproductive cycling, but also regulation of immunity, stress, anxiety and fear,” said Martin. “Interestingly, estrogens can modulate and be modulated by gut microbiota but still relatively few studies have explored them. Much of the research on the gut microbiome's role in anxiety and fear processes has been conducted in male animal models but researchers highlight how a more nuanced and precise understanding of the role the gut microbiome plays in both estrogenic signaling and neuropsychiatric disorders could be immensely impactful for women's health. More research in women is needed to be able to understand the reason for the gender differences, to offer personalized treatment and to be able to prevent mental disease.” 

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Kara Landau, aka The Prebiotic Dietitian, adds her thoughts on the microgenderome. “With a growing interest in the role gender plays on differences in the microbiome, the term ‘microgenderome’ has been used to encompass the science of the variations found and the interaction male and female sex hormones play with the microbiota. Even the bacteria-to-human cell ratio is different between genders, with women having a bacteria-to-human cell ratio of 2.2 compared to men of only 1.3. In one study of 1,135 individuals, females showed greater gut microbial diversity, in particular of the Akkermansia muciniphila being significantly more abundant in females. 

“Given there are also studies showing differences in bacterial makeup in premenopausal and post-menopausal women, it is evident that both gender and lifespan stage, whereby sex hormonal changes occur, are all part of what shape the discrepancies between how illnesses present in males and females,” she said. “Honing in on these differences, and seeking solutions that address those that are associated with poorer mental health, could be a valuable tool for supporting mental wellbeing in the future.” 

A promising but still emerging area of research, additional studies are needed to learn more about the interplay between the gut microbiome and mental health and how these complex interactions differ for men and women. By identifying gender differences in all aspects of health, we can close the gap in so many ways and move from a healthcare system designed around curing sickness to proactive and gender-specific disease prevention.