The only way your central nervous system can get information about the surrounding world is by tapping into the senses and, especially, the gut, which is packed with millions of bacteria.
The gut and the brain talk to each other all the time via different channels and they also influence each other. Nerves before an important event may often lead to a feeling of discomfort in the gut, and likewise, if you do not treat your gut microbiota well and fail to feed those bacteria with the nutrients they need to thrive and live happily, you can feel emotionally quite down.
It might sound a bit scary to think that your emotions and mood, at least to some extent, depend on your gut microbiota and that, in some way, it controls the brain. In fact, this relationship was only discovered two decades ago and, since then, it has become a highly productive field of research. Premsyl Bercik, gastroenterologist and researcher at McMaster University (Canada), is one of the pioneering scientists who discovered and proved that there is a link between mental and gut health.
The GMFH editing team interviewed him to talk about the fascinating new things we have learned in recent months about the so called ‘gut-brain axis’.
Several studies published in 2020 have added more evidence to the innovative hypothesis that gut bacteria can affect behavior and even brain structure.
That’s true. We are learning step by step how this happens. The last available studies have shown there are multiple pathways by which the microbiome interacts with the brain, either through metabolites [waste molecules produced by the bacteria] or direct interaction with the nerves. We have started to pinpoint the bacteria that can have either these positive or negative effects on the brain. Also, from a clinical point of view, if we speak about anxiety, depression, the current medications work only in a certain proportion of patients; we need, for sure, new targets and new approaches. And this also applies, actually, to neurodegenerative disorders. For many of them, we do not have a cure, we really do not fully understand the underlying mechanism. So, the microbiome, again, may offer new insights into the development of the disease.
Are there any clinical trials or studies targeting the gut microbiota to treat disorders or diseases?
Currently there are multiple studies, some very encouraging, although small trials, which suggest that specific bacteria or even FMT—fecal microbiota transplantation—may provide some therapeutic benefit in patients with disorders of the central nervous system.
In 2020, Elaine Hsiao, a researcher at University of California Los Angeles (UCLA), showed in a study published in Nature how maternal gut microbiota modulates fetal neurodevelopment in mice.
It has been already known for some time that the dysbiosis of the maternal microbiome, which is caused either by infections, changes in diet or stress, during the pregnancy can have negative effect on brain function and behavior in the offspring. The study led by Hsiao showed that the depletion and selective reconstitution of the maternal microbiome influences fetal neurodevelopment. This experiment was performed on mice treated with antibiotics or in germ-free mice. What I liked is that they looked at the specific mechanism and they identified changes in the formation of new axons*. These are key for neuron communication, and particularly in certain areas of the brain, such as the thalamus** cortex. This can be prevented by bacteria colonization, which points again to the role of the gut microbiota in early life.
Gut microbiota imbalance has also been related to some neurological diseases, such as Parkinson’s, autism and multiple sclerosis. Also in Nature, researchers from Harvard University identified a new gut-brain connection in amyotrophic lateral sclerosis, or ALS.
ALS is a fatal condition affecting motor neurons of the spine and the brain cortex. We know that apart from the genetic factors, there are also some environmental factors which can play a role. Again, this study showed that in mice with a common ALS genetic mutation, changing their gut microbiome (after using antibiotics or fecal transplants) could prevent or improve disease symptoms. The reason is that there are some bacteria that can stimulate the immune system and as ALS is an autoimmune disease in which the immune system overreacts, reducing the abundance of those bacteria you can improve the systemic inflammation or even autoimmunity and thus, mice mortality. However, these results from experiments on mice need to be confirmed in humans.
Psychobiotics, of which some are probiotics, are strategies that could be used to treat symptoms or even conditions, such as depression or anxiety. They were one of the hot topics of 2020. It is really tempting to think that we might be able to treat depression or anxiety without medication and antidepressants, and for example use probiotics instead.
Psychobiotics is a term coined by the researchers in Cork University, Ted Dinan and John Cryan. Certain probiotics are described as psychobiotics because they have demonstrated an ability to improve anxiety, depression or other symptoms linked to neuropsychiatric or neurodegenerative disorders. We have many pre-clinical trials that show the beneficial effect of probiotics, but I think there is a real challenge to successfully translate this into clinical practice. Moreover, we know there are numerous, usually small clinical trials, which found that probiotics may work, and there are even several meta-analyses showing that these clinical trials may improve these disorders — and particularly they seem to be effective for depression.
But overall, these studies are heterogeneous in respect to their design, clinical outcomes, types of probiotics and also patient cohorts. So, I think that we need to use the same approach we apply for conventional drug testing, for anxiolytics and antidepressants. We need well-designed and reproducible studies to confirm the initial positive results in subsequent larger trials. And, if possible, we need to pinpoint certain biomarkers that will enable us to identify the patients or patient cohorts, for whom these psychobiotics may be effective.