The microbiome sounds like something straight out of science fiction novel. But have no fear, it’s a very real 1.5 – 3 Kg of biological micro-flora existing in your gut exerting a fundamental influence on the health of your entire body, including your brain. In the last decade, studies have unexpectedly linked the gut microbiome to a range of complex behaviours, such as mood and emotion, appetite and satiety, and even learning and memory. Its influence appears to expand beyond maintaining brain function, as it appears it may also influence the risk of psychiatric and neurological disorders, including anxiety, depression and autism.
In a recent talk organised by the Kavli Foundation three scientists leading the field gave their thoughts on where this revolutionary direction in medicine is taking them.
Christopher Lowry, an associate professor in the Department of Integrative Physiology and the Center for Neuroscience at the University of Colorado Boulder and director of the Behavioral Neuroendocrinology Laboratory. Lowry is developing new strategies to prevent and treat anxiety and depression, including the use of beneficial microbes that live in the gut. Sarkis Mazmanian, is a professor of Microbiology at the California Institute of Technology and a 2012 MacArthur Fellow. A microbiologist and immunologist by training, Mazmanian studies how the brain, the immune system and the microbiome interact in health and disease, including its effects on autism spectrum disorder. Tracy Bale is a professor of neuroscience at the University of Pennsylvania School of Veterinary Medicine and Perelman School of Medicine She has been studying the effects of early prenatal stress on fetal brain development and her research has shown that this is partly mediated by the microbiome.
Both Mazmanian and Lowry’s work led them to discover that gut biomes are able to interact directly with the nervous system, seemingly bypassing the immune system.
Mazmanina says: “Since microbes were having such a profound effect on the immune system, I wondered whether they were having an effect on the brain, too. I thought that we would find that microbes interact with the brain via the immune system. But the data we’ve generated so far have shown that microbes interact with the brain by producing molecules that impact behaviour without altering the immune system.” Mazmanian went on to admit they haven’t ruled out an immune link, but that they had discovered mechanisms by which microbial molecules may directly interact with the nervous system.
Chris Lowry’s lab has also been studying the interaction between bacteria in the body and the nervous system and how this affects moods and emotions since 2000. Using an inactivated soil bacterium called Mycobacterium vaccae Lowry found that mice exposed to this bacterium had raised serotonin levels as a response, in effect, creating an anti-depressant effect. He says: “The turning point for looking at gut-microbiome-brain interactions in my lab really came with our first collaboration with Rob Knight, who leads the American Gut Project here at CU-Boulder. Together, we’ve been investigating ways of modulating the immune system to prevent stress-related psychiatric disorders, such as anxiety and mood disorders. Although this work is still in progress, it’s clear that the microbiota plays an important role in stress-induced chronic anxiety, at least in animal models.”
So according to Lowry our gut biome is also perhaps directly responsible for the healthy functioning of our thinking and our overall emotional health by tweaking our brain chemicals. The possibilities of this medically for a new direction in promulgating mental health is promising to say the least.
Tracy bale’s work of late has looked at the effects of the vaginal biome on the health of baby’s as well as the effects of maternal stress on the foetal brain. She explains: “We started thinking about the environmental factors, such as stress, that could change the vaginal microbiome and wondering if that would have an impact on our model of brain development. It blossomed from there because the relationship between a newborn’s gut microbiome and his or her mother’s vaginal microbiome is almost one-to-one, with a newborn’s microbiome changing in direct response to its mother’s. We wondered, how does this interaction alter the way a baby’s brain develops in our mouse model of early prenatal stress?”
On January 15, neuroscientist Christopher Lowry discussed the emerging science, that’s connecting the microbiome – the community of microbes that inhabit the body – with brain health including whether we can treat common brain disorders through the gut.
The resulting research uncovered that stress changes the levels of Lactobacillus, a gut-dwelling lactic acid-producing bacteria that affects the brain’s chemistry, in both mothers and their offspring. Tracy Bale went on to say that now that it is known that the microbiome changes in response to stress, their field is trying to understand the ‘actual’ processes by which the gut microbiome alters the brain. Mazmanian raised the question as to whether such bacteriological interactions could be used to create therapies for Autism as well as other mental health conditions. Could the gut biome be used to treat brain conditions like Autism which today remain largely untreatable?
This begs the question how many conditions seen as purely neurological conditions may actually be derived from changes in the gut biome? Impressive early signs of success are already occurring with Sarkiz Mazmanian claiming they have alleviated some of the effects of Autism already. “In my lab, we’ve been able to alter some of the symptoms associated with autism, such as repetitive behaviors, in mice by feeding them specific bacterial species. These bacteria modulate molecules in the gut and in the blood that affect the nervous system.”
He thinks that the biome is in communication with the brain through one of three pathways. One is the Vagus nerve which is essentially the trunk line connecting the Guts network of nerves with the Brain. The second is through primed immune cells formed in the gut and circulating into the brain and the third method and perhaps the most likely is the production of molecular metabolites into the gut which then circulate through the bloodstream into the brain. “We’ve shown, for example, that a metabolite produced by gut bacteria is sufficient to cause behavioral abnormalities associated with autism and anxiety when it is injected into otherwise healthy mice. This suggests that microbial molecules may connect the gut to the brain via the circulatory system” said Mazmanian.
So the mind-body connection takes on a deeper empirical understanding as we see evidence the gut biome can and does manipulate the base function of our moods and mental functions. Our cells mitochondria routinely swap DNA back and forth, changing for both good and ill the functioning of our bodies and minds, while newly found naturally occurring bacterium may be our next generation of resistance-free antibiotics.
In the face of these discoveries, the monolithic view of ourselves seems to give way to a more conglomerate view of just who and what we are as beings. Perhaps it might be more accurate to see our biological selves as a symbiotic network of living things just as we find in the macro world ecologies. Certainly, science is revealing that the secrets to greater, longer and healthier life seem to rest deeply nested in the trillions of cells and thriving, tiny beings colonising us.