The Nobel Prize-winning, immunology pioneer Élie Metchnikoff postulated over one hundred years ago that manipulating the microbiome with host-friendly bacteria could delay senility. The microbiome, which is the ensemble of microorganisms in our gut, lungs, skin, and other sites, performs a number of functions essential for life. It supplies nutrients, aids metabolism, and defends us against disease-causing bacteria that try to colonize our bodies. In addition to these functions, there is increasing evidence that the 100 trillion microorganisms that inhabit our bodies can influence our moods, decisions and behaviour. Manipulating the microbiome may therefore represent a potential therapeutic target for behavioural disease.
Recent studies have demonstrated that the microbiome can have profound effects on the brain. Mice which are born and raised in a germ-free environment display less anxiety-like behaviours compared to mice raised in germ-containing, but specific pathogen-free (SPF), environments. This result is striking because the gut microbiota, despite its physical separation from the brain, still appears to have a significant and unexpected influence on behaviour. These observations further raise another question: how does the composition of gut microbiota affect behaviour?
Researchers have found that transferring gut bacteria from one mouse strain to another can transfer the strain’s behavioural characteristics. Strains of laboratory mice commonly used in experiments differ in their behavioural tendencies. Some strains of mice show more anxiety-like behaviour than others. To measure anxiety in mice, researchers use an experiment called the “step-down test”. In this test, mice are placed on an elevated platform, and after some time, they will step down from the platform and begin to explore their surroundings. The time it takes for mice to step down is called the latency, and is indicative of anxiety-like behaviour; higher latency is seen in mice that are more anxious. One strain of mice, called BALB/c, naturally displays a much higher latency compared to the NIH Swiss mouse strain. When germ-free, NIH Swiss mice were colonized with microbiota from BALB/c mice, and subjected to the step-down test, the latency was increased compared to NIH Swiss mice with un-manipulated microbiomes, and vice-versa, implying that the higher anxiety behaviour seen in BALB/c was transferred to NIH Swiss mice through its gut microbiome. This increase in anxiety-like behaviour was correlated with a decrease in a biological molecule known as brain-derived neurotrophic factor (BDNF).
BDNF is a protein released by the brain involved in neuronal survival and has been implicated in many psychiatric and neurological diseases such as depression, multiple sclerosis (MS), anxiety, and Alzheimer’s. BDNF has been previously shown to have anxiety-reducing effects, which helps explain some of the changes in anxiety-like behaviour seen in the germ-free, NIH Swiss mice receiving BALB/c gut bacteria.
Therapeutic techniques involving gut microbiota are currently an active area of study in human health. Studies on individuals with MS (a neurological disease in which the protective sheath of neurons are damaged and the ability of neurons to communicate is impaired) showed that fecal microbiota transplantation could have benefici al results in reducing disease symptoms.
Millions of people suffering from psychiatric illnesses including bipolar disorder, depression, and schizophrenia are currently treated with poorly understood drugs with many potential side-effects. Developing alternative treatments through the use of the gut microbiota could potentially provide a safer and inexpensive option. It’s exciting to imagine that the psychiatric treatments of the future might involve administering a tailored formulation of probiotic yogurt, but until then, more research is necessary to further understand the interaction of the microbiota with the nervous system.
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