There are plenty of jokes about so-called man flu, even comedy sketches on YouTube dedicated to the subject. But could biological sex really affect how hard we fall ill? Read Lisa’s article, published in #ion_nutrition Optimum Nutrition Magazine in Spring 2018.

Man flu is defined in the Collins English Dictionary as “a case of the common cold as suffered by a man, implying that he is exaggerating the debilitating effects of the illness”;but a recent article in The BMJ suggested that men may be justified in objecting to this description — as research reveals that men actually have more chance than women of being admitted to hospital and dying as a result of flu. (1)

Dr Kyle Sue, a Canadian GP who found that men were more likely to suffer from respiratory disease and find it harder to shake off a common cold, wrote the article following observations in his own practice. He speculated that the difference in response to the influenza virus was due to the predominantly male hormone testosterone, which suppresses the immune system, whereas the female hormone oestrogen boosts the immune system. 

However, emerging research also highlights the important role played by the billions of bacteria that live in our guts, both in hormone synthesis and immunity, and begs the question as to whether the microbiome (the full genetic make- up of the microbes in the gut) makes a difference to how men and women respond to bacterial and viral infections. 

Male vs. female gut bacteria 

Back in 2013, when scientists realised that there was a difference in the species and quantity of bacteria in the microbiomes of men and women, this area of research was nicknamed: the ‘microgenderome’.(2) 

One study focused on autoimmune diseases such as type 1 diabetes, a disease in which the body’s own immune system destroys the pancreatic cells that produce the hormone insulin.(3) 

Led by Toronto-based microbiome researcher Janet Markle and carried out on mice, the study set out to determine whether different bacteria in the guts of male and female mice had any impact on their risk of developing type 1 diabetes. 

When the mice were manipulated to have sterile guts (i.e. no bacteria), the risk of developing diabetes was the same between the sexes. However, once the mice had bacteria-populated guts (a process that occurs naturally from birth), female mice had a greater risk of diabetes than male mice. 

To find out if this had anything to do with gut bacteria, the team performed faecal transplants, transferring stool from the male mice to the colons of the female mice. With the new ‘male’ microbiome, the female mice started producing fewer of the antibodies that are the cause of type 1 diabetes and had less inflammation of the pancreas. This, Markle concluded, was a result of increased amounts of testosterone in the female mice, which was metabolised by the new bacteria transferred from the male mice. 

Markle went on to conclude that alterations in the microbiome, particularly when we are young, could be sufficient even to overcome any genetic predisposition that we may have to autoimmune diseases. Further research following this line of thought would be needed, but could potentially lead the way for new approaches to prevention of chronic diseases. 

Chronic fatigue syndrome (CFS) 

In the same year as Markle’s study (2013), a team in Australia also made a fascinating discovery into how different species of gut bacteria could influence the symptoms experienced by men and women suffering from CFS.(4) 

This study was a human trial, and focused on three specific bacteria. After measuring symptoms and taking stool samples, it was found that women with higher levels of the bacteria Clostridium had more severe symptoms of CFS, including poor sleep and a weakened immune system. 

Conversely, men fared better with higher amounts of Clostridium, leading to better mood and energy. 

But the reverse situation occurred with the Lactobacillus bacteria. Men with more Lactobacillus had more severe symptoms overall, whereas women appeared to be unaffected. 

Finally, men with higher levels of Streptococcus bacteria tended to have more pain, worse sleep, more gastrointestinal symptoms, less energy, and more severe symptoms overall, whereas women with higher levels of Streptococcus bacteria experienced less pain, and less impaired immunity. 

We could possibly conclude from this that men with CFS should take great caution when taking probiotic supplements, particularly those containing Lactobacillus cultures. 

Irritable bowel syndrome (IBS) 

The microgenderome may also explain why there are differences between men and women in the frequency and severity of IBS. 

The number of women seeking medical advice for IBS is estimated to be three times the number of men. Even considering the accepted reluctance of some men to see the doctor, this is still
a big difference. And according to one study, women were much more likely to have constipation, bloating and abdominal pain as part of their IBS symptoms, whereas men were more likely to have diarrhoea-related symptoms. Whether this is because there are different species of bacteria in the gut is yet to be determined.(5)

Diet and the microbiome 

Looking at the research, there seems to be little understanding of how the microbiomes of males and females could end up being different. A comprehensive review of diet and the microbiome published in the British Journal of Nutrition in 2015 found evidence that type of birth (vaginal or caesarean) and breast feeding all impacted the diversity of the microbiome, as did interacting with a family pet, and that it is from birth to three-years-old when our microbiome develops.(6) After the age of three, the microbiome stabilises and variation of gut species is influenced by long-term dietary changes. 

But one study that may provide some clues as to how male and female gut bacteria could be influenced by diet described an experiment carried out on two species of fish, on mice, and on humans.(7) In each case, scientists found that there were sex-dependant differences in the microbiomes despite the diet being exactly the same for both sexes.

For example, it was observed that when mice were fed a high-fat diet, the male mice developed a wider range of different species in the microbiome than the female mice. This suggests the possibility that the microbiome of males and females may respond differently to fat or carbohydrate in the diet. 

However, there is a long way to go before we fully understand the complex relationship between biological sex, the microbiome, and immunity. However, one study has pointed to an interaction between gut microbes and DNA. Could the microbiome’s clever bacteria just read our DNA and adjust their behaviour accordingly?(8)