We have known for a long long time that we are covered in bacteria inside and out, to the count of 10 – 100 trillion indigenous microbial cells living in symbiosis. Until recently however, the actual identity of the species of bacteria that inhabit us was unknown. With the advent of advanced molecular biology techniques, like 16S RNA sequencing (at a much lower cost and very high speeds), we now know not only what lives in and on us, but also the differences between different body sites, different individuals, and also between the disease and normal state (1, 2).
These days, there is emerging evidence that shows that our microbiota not only exists in symbiosis with our body, but also actively participates in many aspects of our lives, including our development within the womb, as infants and toddlers, right up to adulthood. Gut bacteria produce many products which are transported out of the intestines into the blood circulation, influencing metabolism, the innate immune system and more – this much was known. What is paradigm changing is that these proteins can also cross the blood-brain barrier, influencing the development of the brain, and therefore perhaps behavior (3). It is for this reason that the gut has been christened “the second brain”, connecting the first via the blood stream and the vagus nerve (4). Cutting edge research on the influence of our microbiota on the mind will be presented at a conference in January 2019, aptly called Mind, Moods and Microbes.
When a baby is born, and in the weeks thereafter, its intestinal tract is colonized by trillions of microorganisms. The type and population of the infant gut microbiota is determined largely by exposure to the mother. Babies delivered vaginally and by C-section demonstrate a different population of gut bacteria: the former have a microbiota similar to the mother, whereas the latter’s microbiota are similar to the environment. These differences can persist for years. There is even some evidence that babies delivered by C-section could be more likely to develop autism and ADHD. Other factors that have been shown to affect infant microbiota include antibiotic treatments in early life, breast vs bottle feeding, and maternal stress (5). While there are many factors that impact a child’s motor, social-emotional and cognitive development (genes, environment, diet), it is clear that the gut microbiota may influence this as well . It has been hypothesized that the first two years, during which most of the brain and microbiome development occurs, could be the critical years where neuronal circuits might be best built (5, 6). The finer mechanics of this, and how we can intervene, are being elucidated now, using model systems such as germ-free mice, which show hyperactivity and abnormal social behavior (7).
Depression and the second brain
We all know that depression and other psychiatric issues can occur due to many different things in different people, for example because of chemical imbalances in the brain. However, there is more and more evidence to suggest that gut dysbiosis, or an imbalance in the gut microbiota, might have a role to play. Gut bacteria produce molecules such as dopamine, serotonin and gammaaminobutyricacid (GABA), that can affect the brain, and therefore, behavior. It follows that if the microbiota can play a part in modulating behavior, perhaps ingestion of the proper microbiota might have a positive effect on behavior. Scientists are now working out the possibility of using pro- and pre-biotics to improve mental health by changing stress responses, and reducing symptoms of anxiety and depression – so called “psychobiotics” (8, 9). For example, a species of bacteria called Lactobacillus rhamnosus has potent anti-anxiety effects on animals, and works by altering the expressing of GABA receptors, and also by producing GABA itself. Interestingly, a combination of bacteria seems to be more effective than single species (8), so perhaps in the future, there might be a personalized cocktail of psychobiotics that one can take as part of the treatment regime for psychological issues . These studies are of course, at a very early stage, and currently probiotics absolutely not a replacement for anti-depressants.
Even if you are not clinically depressed, you might not be functioning at your best every day. Laura Steenbergen has made it her mission to find out more about the link between the brain and the gut, and perhaps manipulate this into real life solutions where we can function at our optimal ability.
Eat your way to happiness
Is your diet making you sad? A poor diet, for example one rich in refined, processed foods, sugar, and trans fats, can bring about altered microbiota that can create symptoms of depression and other psychological issues. Recent studies suggest that the Mediterranean diet can help alleviate some symptoms of depression. It is possible that components of this diet may result in a happier mood, including polyunsaturated fatty acids, probiotics, fiber, and the sources of protein (10). Furthermore, evidence suggests that there are key nutrients that are good for the brain, for example, omega-3s, vitamin D, vitamin B’s, magnesium, probiotics and prebiotics. While the field of culinary medicine, and especially nutritional psychiatry, is still in its infancy, it is worth noting that a good diet is nonetheless beneficial to the body as a whole. To this end, Orsha Magyar has founded Neurotrition, a science communication firm and nutrition company fueled by passion and backed by science. Her mission is to help people make the connection that what we eat can impact how we think, feel and perform – while always staying true to what the science and data is currently saying.
A real life “Inside Out”
It is clear that there is mounting evidence that
our gut microbes influence much more of our body and behavior than we
originally thought. Scientists are working hard to make the tangible
connections between the gut and the brain, which can lead to real life
solutions for the millions that suffer from metabolic and psychological
disorders. It is almost disconcerting to realize that our brain and
consciousness might not be our own, but might be controlled by our gut
microbes, leading to a very real interpretation of the words “gut feeling”. In any case, this
is an incredibly exciting time for this field of research, and I am looking
forward to a time when people are able to use scientifically proven therapies,
methodologies and foods to make some real changes to their lifestyles, and see
A word of caution
At the moment however, it should be noted that a
lot of the scientific evidence is very preliminary. We know too little at
present to make any solid recommendations about issues like methods of birth,
breast feeding vs bottle feeding, and diets to the general public. Therefore,
any product or method that claims to provide benefits to the microbiota should
be viewed with a dose of healthy skepticism. John Cryan and Timonthy Dinan,
leading researchers in the field, have said of psychobiotics:
“We must, however, sound a note of caution. Despite marketing claims to the contrary, most putative probiotics have no psychobiotic activity. Until recently, lax regulation in both the US and the European Union allowed manufacturers to make outlandish claims without supporting data. This situation is changing and will protect consumers from fraudulent marketing, but the reality is that only a small percentage of bacteria tested have positive neurobehavioural effects. Some bacteria fail to survive storage in the health food store or are eliminated by acidity in the stomach. Even if they do survive gut transit, they may be devoid of health benefits.” (Quoted from 8)
So what can we do, right here and right now? From what we know so far, making healthy life choices when it comes to food, exercise and stress management seems to be key to keeping your microbes, and eventually you, happy. Admittedly, we already knew all this, but now at least there is more and more scientific evidence that this really does work!
Defining the Human Microbiome (Luke K Ursell, Jessica L Metcalf, Laura Wegener Parfrey, and Rob Knight) Nutr Rev. 2012 August ; 70(Suppl 1): S38–S44. (DOI: 10.1111/j.1753-4887.2012.00493.x.)
The human microbiome in evolution (Emily R. Davenport1, Jon G. Sanders, Se Jin Song, Katherine R. Amato, Andrew G. Clark and Rob Knight) BMC Biology (2017) 15:127 (DOI: 10.1186/s12915-017-0454-7)
The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior (T Arentsen, Y Qian, S Gkotzis, T Femenia, T Wang, K Udekwu, H Forssberg and R Diaz Heijtz) Molecular Psychiatry (2017) 22, 257–266 (DOI: 10.1038/mp.2016.182)
The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis (Bruno Bonaz, Thomas Bazin, and Sonia Pellissier) Front Neurosci. 2018; 12: 49 (DOI: 10.3389/fnins.2018.00049)
Fetal, neonatal, and infant microbiome: Perturbations and subsequent effects on brain development and behavior (Rochellys Diaz Heijtz) Seminars in fetal and neonatal medicine 21 (2016) 410 – 417(DOI: 10.1016/j.siny.2016.04.012)
Programming Bugs: Microbiota and the Developmental Origins of Brain Health and Disease (Martin G. Codagnone, Simon Spichak, Siobhain M. O’Mahony, Olivia F. O’Leary, Gerard Clarke, Catherine Stanton, Timothy G. Dinan, and John F. Cryan) Biological Psychiatry January 15, 2019; 85:150–163 (DOI: 10.1016/j.biopsych.2018.06.014)
Normal gut microbiota modulates brain development and behavior (Rochellys Diaz Heijtza, Shugui Wang, Farhana Anuar, Yu Qiana, Britta Björkholm, Annika Samuelsson, Martin L. Hibber, Hans Forssberg, and Sven Pettersson) PNAS February 15, 2011, vol. 108 no. 7, 3047–3052 (DOI: 10.1073/pnas.1010529108)
Psychobiotics: how gut bacteria mess with your mind (25 January 2014, NewScientist, 29.) https://www.newscientist.com/article/mg22129530-400-psychobiotics-how-gut-bacteria-mess-with-your-mind/
A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood (Laura Steenbergen, Roberta Sellaro, Saskia van Hemert, Jos A. Bosch, Lorenza S. Colzato) Brain, Behavior, and Immunity 48 (2015) 258–264 (DOI: 10.1016/j.bbi.2015.04.003)
Feeding melancholic microbes: MyNewGut recommendations on diet and mood (Timothy G. Dinan, Catherine Stanton, Caitriona Long-Smith, Paul Kennedy, John F. Cryan, Caitlin S.M. Cowan, María Carmen Cenit, Jan-Willem van der Kamp, Yolanda Sanz) Clinical Nutrition (DOI: 10.1016/j.clnu.2018.11.010)