All the microorganisms present in the gastrointestinal tract, including bacteria, viruses and fungi, are collectively known as the ‘gut microbiota’. Because our gut microbiota play an essential role in immunity, homeostasis, neurodevelopment and metabolism, a disruption of this complex system can have a knock-on effect on health

Important variables affecting the balance of the gut microbiota include diet, race, age, exercise, genetics, mode of delivery and medications. Another confounding variable which is gaining traction in current research is sex. While results are inconsistent (some studies showed no sex differences), several animal and human studies have shown sex differences in gut microbiota, suggesting the need to consider this biological variable when conducting research into the microbiome.

The following blog post will look into sex differences which have been identified in the gut microbiota, factors affecting these sex differences and the role sex differences play in disease associated with the gut microbiome.

The Definition of Sex in Science

In the realm of biomedical science, the term ‘sex’ refers to the “biological classification of a species based on its reproductive systems and the functions derived from a chromosomal type or hormones” (1).

It’s important to note that this definition differs to that of ‘gender’ which refers to the personal and cultural attitudes and behaviours associated with a person’s sex, shaping one’s understanding of what it means to be male or female.

Differences in Gut Microbiota of Males and Females

Although much of the research into sex differences in gut microbiota is conflicting, there is evidence to show that males and females have differing gut microbe profiles.

It’s widely reported that there are 10 times more microbial cells in the human body than human body cells. Refuting this claim, a recent study has reported that the number of cells in the gut microbiota are in fact similar to the number of human body cells and that there is a slight difference in the ratio of human cells to bacterial cells between sexes (2).

The types of bacteria residing in the gut also differ by sex according to various studies (9)(10)(12), evident even in the early years of human life. For example, in one study (17), differences in a bifidobacteria abundance (a bacteria associated with health benefits to the intestine) were observed in male and female babies from birth to six months of age. In particular male infants had higher bifidobactrium levels at the first day of life compared to fe.

Another difference between the sexes is the speed at which the microbiome matures. Just as females are generally considered to mature faster than males, the female microbiome appears to mature earlier than the male microbiome. In a similar vein, changes occurring in brain development which help to improve brain function occur earlier in females than males (8). Given the well studied link between the gut and the brain, one could postulate that the gut-brain axis plays a role in the differences in brain development between the sexes.

Differences in response to supplement consumption has been shown to differ between the sexes. Vitamin A is a supplement that plays a key role in establishing the intestinal microbiome and immunity, with its deficiency being associated with impairment of the gut lining. In one study (18), males receiving vitamin A had increased levels of Bifidobacterium – known to increase levels of key immune cells – in the gut than males receiving placebo, while females did not show these differences, demonstrating an interaction between testosterone and vitamin A. The interplay of certain factors, such as vitamin A supplementation, with sex hormones and immunity may be a possible explanation of sex-dependent gut microbiota differences.

Based on the evidence that sex-related differences aid in the development and diversity of our microbiomes, understanding the various factors which affect sex differences is a step towards health advice tailored to the individual.

Factors Affecting Sex Differences in Gut Microbiota

Hormones

Studies have shown that some sex differences in gut microbiota do not appear until puberty, suggesting sex hormones may be a strong driver of differences in the microbiome of males and females.

In an animal study, the microbial diversity before and after puberty were the same in female mice, whereas the composition changed after puberty in male mice, suggesting sex hormones could play a role in the sex differences in gut microbiota of mice. Interestingly, when the source of the male hormone was removed via castration, the gut microbiota of the castrated mice was similar to that of a female mouse rather than a male mouse (4).

The effect of sex differences on the gut microbiota can be seen via an experiment conducted using faecal microbiota transplantation in mice. After transplanting the same feces from a female mouse into male and female germ-free mice, the gut microbiota after puberty clustered according to the sex of the recipient mice (5).

Sex differences in the microbiomes of humans attributed to hormonal influences have also been observed in human studies. Interactions between the hormone estrogen and gut microbiota was observed in females whose ovaries had been removed, leading to an increase in the abundance a microbe called Clostridium bolteae. (1) Gut diversity in the post-meonapual female can also be significantly altered by metabolites that are structurally similar to estrogen, increasing the concentration of a certain type of microbe while suppressing another (1)

Puberty is a time when hormone changes are occurring at full force, so the fact that microbial changes have been observed between the sexes at this significant time suggest that hormones such as estrogen and testosterone may play an important role in microbial development and diversity.

Drugs

Drugs, such as antibiotics have a significant effect on the gut microbiota. Some illnesses are predominant in one sex, thus males and females have different patterns of medication use. For example, a study in the Netherlands (6) showed that males were more likely to be taking drugs for heart disease, whereas females were more likely to be taking opiates, laxatives and antibiotics, all of which affect the microbiome in different ways.

Diet

Diet is one the most significant factors responsible for shaping the microbiome. Research has identified that males and females show sex-specific responses to the exact same diet (11), a salient revelation given how strong an influence diet has on health and disease.

Differences in hormonal status and microbial composition between males and females can be influenced by the type of diet consumed. For example, a stronger effect is seen with a cereal-based diet in males and a high-fat diet in females (4). Effects of prebiotics on gut diversity has also been shown to be different between the sexes (13), i.e. fibre intake affects estrogen levels, thereby changing the gut microbiota.

BMI

According to various studies, changes in body weight are associated with alterations in the number of microbes living in our guts and differences in these alterations are evident between the sexes. For example, in a Western study (10), the relationship of the BMI with gut microbial composition was significant in females, but not in males. In an Eastern study (14), the diversity of gut microbiota was significantly higher in an underweight group than in the other BMI groups, but in the females only. Also, the relative abundance of a certain type of bacteria was higher in obese males, whereas that of another type was higher in obese females.

The effects of estrogen on the composition of the microbiome are well documented, so given that adipose tissue is the main site of a certain type of estrogen synthesis (15), especially in postmenopausal women, total body fat content may play an additional role in gut diversity based on sex.

Bowel Movements

How fast stool moves through the gut is an important factor determining the gut microbiota composition and metabolism with differences in bowel function and transit being observed between the sexes.

The speed at which stool passes through the gut is strongly correlated with stool consistency; the looser the stool the faster the transit, the harder the stool, the slower the transit. In each case, the amount of certain types of microbes present in the gut differs which is interesting given that some studies have shown that in general females have slower colonic transit time and harder stool than males (16).

Gut Microbiota and the Influence of Sex in Disease

Based on evidence showing sex-related differences in our microbiome and how they interact with various systems within our body, it makes sense to infer that diseases will present differently between the sexes.

For example, irritable bowel syndrome (a risk factor for cardiovascular disease) and autoimmune disease coincide with a dysbiosis of the gut microbiome and are more prevalent in females. Conversely, more than two times more males than females are affected by antisocial personality disorder (3).

Protective pathways for certain diseases such as type 1 diabetes have been shown to be triggered by changes in hormone levels related to interactions with the gut microbiota indicating a causal relationship between sex hormones, gut microbiota, and control of autoimmunity.

While a number of studies have shown links between gut microbiota and health disorders, more research is required as to whether sex-dependent gut microbiota is connected to disease susceptibility.

Conclusion

Research is beginning to reveal important sex differences in the gut microbiota that may well have a powerful impact on health practices. While the significance is evident, more research is required in order to fully understand the mechanisms involved in these sex-dependent differences.

As in life, when it comes to our guts, one sex doesn’t prevail over the other. Rather it’s about acknowledging how lifestyle factors and medical treatments can be tailored with sex differences in mind so as to optimise the health and wellbeing of the individual.

Brigid xx

 

References

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