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Many of us have experienced the feeling of our ‘stomachs turning’ when we are nervous, scared or anxious, and there is good reason as to why this happens. The gut, often referred to as our second brain, plays an important role, not just in digestion, but also regulating the activity of our nervous system. You may have noticed this during stressful periods; perhaps your bowel habits might change, and maybe you lose your appetite, or even get stomach cramps. You can thank your ‘Microbiome-Gut-Brain Axis’ for this. This is a key process of communication between our gut, gut bacteria (microbiome) and our nervous system, stimulated by the vagus nerve, otherwise known as the ‘wandering nerve’. This nerve connects the brain to all the organs that it passes on its way down to the colon, where most of the microbiome can be found. It works by constantly sending messages, informing the gut bacteria what is going on in the environment, allowing for them to react accordingly.[i],[ii]
The billions of gut bacteria that reside in our body, mainly in the digestive tract, have a symbiotic relationship with us. We are now discovering just how important these bacteria are to our health, and that includes mental health! Our gut bacteria can produce numerous neurotransmitters,[iii],[iv] which affect our nervous system and subsequently our behaviour.[v] The importance of gastrointestinal health to nervous function has been highlighted by a study which found that out of more than a thousand people with gastrointestinal disorders, 84% suffered with anxiety, and 27% with depression.[vi]
Given the prevalence of ‘stress’ and related conditions in today’s society, there is a need for us to consider how our gut microbiota may modulate our stress levels. The impact of gut bacteria on the hypothalamic-pituitary-adrenal (HPA) axis - the core stress axis – has been indicated by clinical trials showing that probiotics improve anxiety[vii] and reduce cortisol[viii] (a hormone which is usually high during a stress response).
Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter (chemical messenger) which promotes a feeling of calm.[ix] Dysfunctions in the GABAergic pathway are associated with anxiety.[x] Animal research has shown how certain probiotic strains of Lactobacillus and Bifidobacterium (including Lactobacillus rhamnosus),[xi],[xii] and the LAB4 combination[xiii] (two strains of Lactobacillus acidophilus, Bifidobacterium lactis and Bifidobacterium bifidum) can produce GABA. This research highlights the therapeutic potential of communication between our gut microbiota and our body, termed ‘inter-kingdom signalling’.[xiv]
Serotonin is a neurotransmitter that is sometimes called the ‘happy hormone’ as low levels are linked to low mood, depression[xv] and anxiety.[xvi] More than 90% of serotonin is produced in the gut! Animal studies have shown a potential regulatory effect of the gut bacteria on its production, as serotonin levels are significantly reduced in germ-free animals (animals that have a sterile gut). An explanation may be the short chain fatty acids (SCFAs) and secondary bile acids that are produced by our gut bacteria, may enhance serotonin synthesis.[xvii] Preliminary animal research indicates that B. infantis may increase plasma tryptophan levels; a precursor to serotonin, and thus potentially increasing serotonin levels.[xviii] So, targeting the gut microbiota may be useful in potential serotonin-related disorders, such as depression.[xix]
Individuals with depression have been found to have a different microbiota composition in comparison to healthy subjects, indicating disruption to the microbiome.[xx] Research using various probiotic combinations of different Lactobacillus and Bifidobacterium strains shows a positive effect on mood in both normal and depressed adults.[xxi] The LAB4 combination can also reduce anxiety levels.[xxii] This effect appears to be primarily modulated via the serotonergic and GABAergic pathways.
A depletion in gut bacteria (due to antibiotics) is associated with signs of cognitive decline and altered production of Brain-Derived Neurotrophic Factor (BDNF) and tryptophan (a pre-cursor to serotonin).[xxiii] BDNF is important for the survival of existing nerve cells and plays a vital role in learning and memory. Changes to gut bacteria have also been noted in children with autism, particularly increased levels of Clostridium species[xxiv] and Bacteroidetes, and lower levels of Bifidobacterium.[xxv] If gut dysfunction is a key factor in autistic spectrum disorder, then probiotics may offer some hope. Certain probiotics like L. acidophilus and L. rhamnosus help to support healthy gut microflora[xxvi] and reduce overgrowth of C. difficile,[xxvii] while LAB4 significantly improved short-term memory in animals.[xxviii]
Other mechanisms by which gut bacteria may affect the central nervous system (CNS) include increased gut permeability (or leaky gut syndrome) leading to bacteria and toxins moving into areas in the body where they are not normally found and potentially moving across the blood-brain-barrier. In fact, the microbiome may be partly responsible for permeability in the CNS.[xxix]
Bacterial metabolism can produce molecules such as lipopolysaccharides (LPS), d-lactate, ammonia and other toxins, which coupled with increased intestinal permeability can increase systemic inflammation. Elevated LPS levels have been found in individuals with depression.[xxx] D-lactate can increase brain inflammation[xxxi] and has been connected to panic attacks[xxxii] and schizophrenia.[xxxiii] One study found higher levels of d-lactate-producing Enterococcus and Streptococcus species in chronic fatigue syndrome (CFS).[xxxiv] One recent study showed a correlation between increased size of brain regions and changes in the gut microbiota (higher Firmicutes, especially Clostridium and lower Bacteroides) in people with IBS, speculating that bacterial metabolites could induce specific changes in the brain.[xxxv]
Further research is needed to determine exactly how probiotics can affect mental health in humans, but for now, it is an empowering prospect. By altering the gut bacteria for the better, it may be possible to improve your brain health. It encourages us to think laterally about possible stressors on the microbiome, such as caesarean birth, antibiotics and processed food. Supporting neurotransmitter balance and reducing intestinal permeability with probiotics may help us to combat today’s rising number of mood and anxiety disorders.
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[ii] Bravo JA et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS. 2011; 108 (38): 16050-16055.
[iii] Lyer LM et al. Evolution of cell-cell signalling in animals: did late horizontal gene transfer from bacteria have a role? Trends Genet. 2004;20:292-299.
[iv] Valles-Colomer, M et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology (2019).
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