Microbiomes and mental health
People raised in cities, with less animal contact and a narrow range of microbial exposures, are more prone to health issues...
The microbiome is a term that defines the assemblage of microorganisms that populate almost every body part. Its composition varies markedly over time and between individuals and is influenced by the environment, such as the people and other animals we live alongside. Not only do these microorganisms keep us company througout our lives, they also play an essential role in helping us to remain healthy. And alterations in the makeup of the microbiome can lead to increased disease risk. The ‘old friends hypothesis’, suggests that changes in lifestyle, coupled with urbanisation and an over-obsession with sterility, have reduced natural exposure to microbes that inhabit our surroundings. This can leave us lacking precious health allies.
It's a fact that the microbes that cause potentially lethal infectious diseases, and friendly microbes that prevent allergic and autoimmune conditions, frequently share the same environments, and their equilibrium is a delicate one. Before the sanitary revolution of the 19th Century, which swept clean the lives of those living in developed countries, the mortality rate for infectious diseases, especially in early childhood, was a lot higher than today. In low-income countries, where hygiene conditions are still weak - half of the population of India currently has no access to a toilet, for instance - this situation continues. But what is not common in less developed countries - and less salubrious living conditions - are cases of allergic or autoimmune diseases. It appears that improvements in sanitation processes, coupled with higher quality food and cleaner water, has resulted in a rapid decline in infectious diseases but an upswing in allergy.
Cleaner living, scientists believe, has inadvertently reduced our exposure to friendly microbes that occupy the same niches as disease-causing pathogens. In cleaning up our acts, we have deprived our bodies of the essential lessons they need to learn to tell friends from foes. Consequently, innocuous agents, such as pollen, house dust and food allergens, are regarded with immune distrust. And now scientists have added a new twist to this ‘old friends’ puzzle: there may also a link between lack of contact with specific microorganisms and prevalence of depression in modern cities.
Studies have shown that the gut microbiome seems to influence the central nervous system (CNS). Several studies have shown that a weak immune system, due to lack of early contact with microbes in natural environments, is associated with increased vulnerability to mental health disorders. Cities have previously come under scrutiny as causes of depression and psychological problems; the finger has been pointed at factors like excessive lifestyle and isolation as the cause, and these aspects are almost certainly implicated. But human and animal studies are now demonstrating that exaggerated immune responses might also play a role in the development of mental disorders. So do our microbes influence our happiness as well?
In reality, human behaviour is influenced by several factors, including immunological, endocrine, and metabolic mechanisms. All of those are, at the same time, affected by the microorganisms that make up our microbiomes, suggesting an active role for our microbes in processes linked to brain development and physiology, psychology and behaviour. In 2018 scientists from the USA and Europe published breakthrough research demonstrating that an individual's early environment impacts on the capacity of the immune system to respond to stress stimuli later in life. Groups of healthy young men who had spent the first 15 years of their lives either in contact with farm animals in rural environments, or who had been raised in urban environments without pets, underwent to a series of standard psychosocial stressors tests. The immune system activation was measured before and after. Participants that grew up in cities, and without daily contact with animals or the natural landscape, showed a more pronounced immune activation in response to laboratory tests measuring social stressors compared with participants that grew up around farm animals. The researchers didn’t find differences in perceived life stress between the two groups, leading them to conclude that increased risk of both inflammatory and mental disorders in urban youth is due to the lack of contact with animals and their microorganisms.
More insights came earlier this year when a Dutch research team published a paper in Nature Microbiology. They analysed the role of the gut composition in a broad range of psychiatric and neurological disorders using ultra-modern sequencing technologies. The researchers examined the microbiota composition in depressed patients and correlated it with their perceived quality of life. From the data, they realised that there are specific gut bacteria that are associated with the mental state of the patient. Specifically, they found that two groups of microorganisms, Coprococcus and Dialister, are present in the guts of patients that report a good quality of life but depleted in patients with treatment-free depression. Other organisms, like Butyricicoccus, were also linked to antidepressant treatment.
“This is an association that we have repeated in three independent cohorts of patients: it shows a diagnostic potential,” says Professor Jeroen Raes, the lead author of the study.
So who populates our microbiomes, which is a consequence of our life histories, can make a difference to our mental health. But is it all to do with who lives in our inner body? Depression and other nervous system diseases are complicated and multifactorial, and we are a long way from using "microbiota pills" to cure depression. The studies done in the field so far have mostly shown a correlation between the presence or absence of specific groups of microorganisms and certain mental health states. Now we need to prove that this relationship is causal before we can develop new therapeutic approaches for these conditions. "We have at least other 15 years of studies to go," says Raes.
Thankfully, it's not too late for anyone! “It doesn’t have to be an upbringing in the farm environment,” says Graham Rook, Emeritus Professor of Medical Microbiology at UCL and one of the leaders of the microbiome field. Brief exposures to nature, like a 90-min walk in a natural setting, or having a pet in the house, can help to get back in touch with healthy microbes. And maybe a summer holiday on a farm might be enough to make everyone happy: our immune system, our nervous system and also the kids. At least this might stop them playing video games for a bit!