The Gut Microbiome-Brain Axis
Ever wonder why your stomach is “tied in knots” when you’re going to an important meeting or just about to deliver a presentation? Gut symptoms are one of the most common signs of anxiety and stress.
The connection between the gut and the brain has been deeply embedded in our collective unconscious, with many common idioms such as “gut feeling” or “gutted”, reflecting the popular beliefs. Now, the interaction between these seemingly distant organs, gut and the brain has been backed up by research and we’ve also started to appreciate the role that the gut microbiome (the collection of all microbes in the gut and their genetic material) plays in it.
How do the gut microbiome and brain communicate?
Several pathways of two-way signalling between the gut microbes and the brain have been discovered. Communication is mediated by a combination of the immune, enteric, and neural pathways that provide physical and chemical connections between the brain and the gut.
Each of us has a very unique set of gut microbes, and there is a huge inter-individual variation in their composition. These gut microbes not only aid our digestion, strengthen our immune system and prevent GI infections but also communicate in a bidirectional way with our brain, affecting our mood and behaviour.
The brain regulates the functionality of the GI tract, with some of its aspects controlled also by the enteric nervous system located in the gut. Indeed, not only the gut receives information from the brain, but the gut microbiome produces or stimulates the production of neurotransmitters and other neuroactive compounds, which affect brain function.
Did you know that approximately 90% of serotonin and 50% of dopamine is produced in your gut? 90% of the communications between the two runs from the gut to the brain. In addition to communicating with the brain by using nerve connections and molecular signalling, the gut microbiome modulates the immune system, contributing to neuroimmune modulation. So, the brain is quickly updated about what happens in the gut.
On the other hand, the gut microbes know when we feel happy, stressed, anxious and readily respond to that. For example, experiencing stress may impact the profile of the gut microbiome.
Which brain related ‘disorders’ have been associated with the gut microbiome?
The role of the microbiome-gut-brain axis has been extensively researched in the context of stress, learning, memory, mood and satiety. It's only recently been recognised that disruption in the gut microbiome composition is frequently associated with a variety of psychological and neuropsychiatric disorders, such as anxiety, depression, autism spectrum disorder, schizophrenia, Alzheimer’s and Parkinson’s disease. Interestingly, diseases which used to be linked solely to the gut, such as IBS, have co-existing psychosocial symptoms such as stress, anxiety and depression.
Diet is one of the key factors that shapes the microbial composition during infancy and throughout life, thereby affecting brain structure and function, the scope of this article is to demonstrate how we can modulate the microbiome-gut-brain axis by changing nutritional components of our food.
What role does the gut microbiome play in healthy brain development?
The first three years of life are critical for brain development and for the gut microbiome maturation from generally being rich in bifidobacteria into an adult-like composition. It’s understood that disruption of the gut microbiome composition during any of the critical neurodevelopmental phases (when the brain is very susceptible to changes in the environment and diet) may have detrimental effects on mental health. This is because key processes associated with brain plasticity such as new nerve cell generation are regulated by the gut microbiome. So, the gut microbiome not only directs brain function but also impacts on neurodevelopment.
Scientists have discovered a lot about the role of the gut microbiome for the brain by using mice deprived of any germs. They reported that these germ-free mice have had much lower levels of factors important for brain development and function and had changes in size of critical brain structures for processing emotions and memory.
The new research brings up the tantalizing possibility that by shifting the gut bacteria towards higher levels of the beneficial species such as bifidobacteria, beneficial conditions for optimal brain development can be achieved. Researchers from Oxford University demonstrated that in very young animals supplemented with Bimuno® (a fibre that was demonstrated to increase bifidobacteria numbers), higher levels of neuroprotective molecules were detected in their brain1. More research from the same group demonstrated that Bimuno not only works at the early life stages but also stimulates release of neuroprotective compounds in adult life2. These molecules are beneficial for the brain as they enable more connections between the nerve cells, higher brain plasticity, and associated with it the potential for better learning and memory.
What role does the gut microbiome play in brain functioning in adulthood?
The gut microbiome continues to play an important role throughout our entire life. According to research, the gut microbiome undergoes significant changes once we reach old age, with some beneficial species, such as bifidobacteria, decreasing in numbers and overall reduction in microbial complexity. That shift within the bacterial community is linked with increased inflammation and increased gut permeability. In general, ageing is characterized by low grade chronic inflammation, with pro-inflammatory molecules present in elderly people's blood3.
These changes in the gut microbiome and higher levels of inflammation are not good for our brain and have been linked with an increased risk of some diseases such as Parkinson’s and Alzheimer’s disease.
A team of researchers injected gut bacteria from humans with Parkinson’s disease into germ-free mice and reported a rapid deterioration with symptoms resembling human Parkinson’s disease4.
To prevent or alleviate the age-related changes to the gut microbiome and inflammation, researchers have tested dietary modifications involving higher fibre intake. For example, it’s been demonstrated that in healthy people aged 64 years and over, supplementation with Bimuno affected the gut microbiome by increasing levels of beneficial bifidobacteria. Meanwhile, those on Bimuno had decreased levels of proinflammatory and increased anti-inflammatory molecules and demonstrated improved immune system capabilities in dealing with removing pathogens and cell debris3.
Why does looking after your gut microbiome in later-life matter?
As mentioned earlier, a balanced gut microbiome and well-functioning immune system is important for brain health. It’s not only true in old age, as research has shown that imbalance in the gut microbiome is associated with psychological problems, such as anxiety or depression. Researchers demonstrated that how we cope with stress is gut-brain axis dependent, for example by showing that healthy adults who took a fibre supplement, Bimuno, paid less attention to negative information and had lower levels of cortisol, a stress hormone which is linked to anxiety.5
How does the gut microbiome affect sleep?
Our gut microbiome has its own daily rhythms, which work in synergy with our sleep and wake cycles. The daily rhythms of the gut microbiome are tightly linked to our dietary patterns, frequency and timing of meals, which affect their composition and metabolic activity. In return, the gut microbiome seems to affect our immunity, metabolism and sleep. So, both gut microbiome and our brain play a role in our biological rhythms.
When travelling to different time zones (jet lag), doing shift work, suffering from sleep deprivation, we disrupt not only our biological rhythms, but also our gut microbes. Given that the gut microbes are responsive to when we eat, by eating irregularly, we disturb them. Consequently, gut microbiome diversity is compromised, with increased levels of bacteria that are associated with inflammation and occurrence of leaky gut. Research has found a clear link between disrupted gut-microbiome equilibrium (called gut dysbiosis), disruption of microbiome rhythms and host metabolic syndrome6. Gut dysbiosis can be ameliorated by dietary adjustments focused on increased prebiotics or probiotics intake to shift the balance of the gut bacteria.
Although it’s widely recognised that a balanced gut microbiome supports a healthy brain and vice versa, one of the unmet needs in this field is the understanding of causality of the gut microbiome interaction with the host brain. So far, much of what we know about the microbiome-gut-brain axis is based on correlations between specific gut bacteria, their metabolites and neurological symptoms, which mostly stem from animal studies. It’s an exciting field opening the possibility of developing interventions which by targeting the gut microbiome influence our brain.
- 1 Williams S, Chen L, Savignac HM, Tzortzis G, Anthony DC, Burnet PWJ (2016). Neonatal prebiotic (BGOS) supplementation increases the levels of synaptophysin GluN2A-subunits and BDNF proteins in the adult rat hippocampus. Synapse 70:121-4.
- 2 Savignac HM, Corona G, Mills H, Chen L, Spencer JP, Tzortzis G, Burnet PW. (2013) Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochem Int. 63(8):756-64.
- 3 Vulevic J, Drakoularakou A, Yaqoob P, Tzortzis G, Gibson GR. (2008). Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers. Am J Clin Nutr. 88(5):1438-46.
- 4 Sampson TR, Debelius JW, Thron T et al. (2016) Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016 Dec 1;167(6):1469-1480.
- 5 Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PW. (2015). Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl). 232(10):1793-801.
- 6 Thaiss CA, et al. (2014) Transkingdom control of microbiota diurnal oscillation promotes metabolic homeostasis. Cell, 159:33; 514-529.
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