By Asra Shah
Most people have experienced situations where they have “gone with their gut”, but have you ever wondered what that means? In such situations, unexpected signals are received from a “second brain” hidden deep in the walls of the digestive system—the Enteric Nervous System (ENS), a main division of the Autonomic Nervous System (ANS). The ENS consists of a wide network of neurons that control functions of the gastrointestinal (GI) tract. It is incapable of thought processing, but controls digestion and communication with the brain an efficient manner.1
There are over 1000 microbes in the gut, most of which are anaerobic bacteria. The intestinal microflora are important to the human body, with functions in processes including bowel movement, food digestion and nutrient absorption. Everyone’s gut microbiota has a specific composition as it is highly influenced by genetics, growth, and development.2 The brain and gut work in a bi-directional manner, affecting each other’s functions. This has prompted several studies into the importance of microbiomes in managing mental health issues. Gut commensals send signals to the Central Nervous System (CNS) under both stable and stressful conditions; this occurs by neurogenesis, neurotransmission, neuroimmune, neuroendocrine and sensory-neural pathways. 2
For decades, it was believed that mental health conditions like anxiety and depression contribute to problems like constipation, bloating, stomach pain and irritable bowel syndromes; recently , it has been demonstrated that this link is bidirectional.1 Specifically, it was reported thatan irritation in the GI tract sends signals to the CNS, triggering mood changes.1 Feelings of sadness, anger, anxiety or elation trigger gut contractions or enzyme release, leading to pain or bloating in the abdomen.3
Studies have demonstrated that for every disease, including mental health illnesses, there is a specific microbe involved.2 This highlights the intimate gut-brain connection which is powered by the vagus nerve that allows free flow of messages in both directions.
On stress exposure, major energy resources are directed to the brain and muscles. Cortisol release affects the gut microbiome by preventing the vagus nerve from reacting effectively to inflammation.4 In one study, rodents, those receiving faecal samples from patients with major depressive disorder (MDD) developed depression and rodents who experienced stress and depression showed a reduction in gut microbiome content and diversity.2
Similarly, imbalance in the gut microbiome affects overall mood. A diverse and balanced gut microbiome is important for preventing opportunistic bacteria from taking advantage of the uninhabited area and causing inflammation.4 Alterations in the gut microbiome composition trigger microbial lipopolysaccharides (LPS) production, which activates inflammatory responses. Cytokines send signals to the vagus nerve, which links to the hypothalamic-pituitary-adrenal axis, causing behavioural effects.2 Research suggests that the GI tract’s inflammation leads to neuroinflammation, fuelling microglial action and triggering the kynurenine pathway to induce depression. The bidirectional connection between gut microflora and depression has been established, but the direction of causality between the two entities has not yet been determined.
New research reveals that prolonged neuroinflammation affects brain functions, dictating one’s mood and behaviour. The interaction of depression and inflammation is a vicious cycle: inflammation triggers cytokine production due to external stressors, and poor diet and lack of exercise hastens the inflammatory reaction, worsening depression. Any stressful events experienced affect the diversity and composition of gut commensals. Thus, recurrent and chronic inflammation affects mental and physical conditions.2 Gut bacterial activity affects stress and anxiety, with a balanced gut microbiome improving stress resilience ,and an imbalanced one affects mental health.4
Butyrate is an essential short chain fatty acid (SCFA) produced by the healthy gut bacteria . It is the main fuel source for cells of the gut lining and helps keep this barrier intact to prevent inflammation. In dysbiosis, gut bacteria might reduce production of important nutrients, including butyrate.4 SCFAs communicate with serotonin-producing cells to control levels of anxiety and happiness. Similarly, Gamma-Aminobutyric Acid (GABA) regulates and improves mood by calming the nervous system and switching off stress reactions.4 Diet choices significantly affect body systems –such as the endocrine, immune and gastrointestinal systems – as this contributes to butyrate production.2,4 High-fat consumption causes obesity and inflammation of body systems. The gut microbiome can only alter the harmful effects of the high-fat diet and maintain mood up to a point. Anxiety and depression can be decreased by modulating gut microbiome composition through proper nutrition and probiotics.2
Probiotics help maintain a balanced gut ecosystem and preventing dysbiosis by allowing healthy bacteria to thrive and contribute to butyrate production. Certain probiotics even produce GABA. Probiotics like species in the Lactobacillus, Bifidobacterium, and Lactococcus genera improve mental health, stress resilience, and anxiety, and can reduce symptoms of depression.4The use of supplemental probiotics has shown reliable effects on resolving brain-associated problems; however, more research is needed to ascertain their mode of action and side-effects.2 Similarly, prebiotics directly provide sustenance to gut bacteria as they contain fibre which transforms into SCFAs like butyrate. Thus, increasing prebiotic intake may positively affect mental health as it is associated with reduction in anxiety-related behaviour.4 Essentially, it is shown that healthy diet helps gut bacteria to protect mental wellbeing because eating the right foods feeds happy bacteria and presence of healthy bacteria, diversifies the gut microbiome which produces substances which increase mood-lifting chemicals, like serotonin and GABA.4 A large-scale clinical trial showed insignificant effects of the Mediterranean diet (healthy eating) on adult behaviour with subclinical manifestations of depression. However, improved depression symptoms were noted on shifting the current diet to the Mediterranean diet in small-scale clinical trials.2
The effects of gut microbiota on mental health is a relatively new research topic and needs to be delved into further. More laboratory experiments must investigate the composition, qualities, and concentrations of gut microorganisms that affect behaviours associated with mental health illness; we are still far from fully characterizing the role of gut microbes to our thought process.2 Once fully understood, the hurdles in the management of intractable psychiatric diseases will be overcome more easily.
References:
- The brain-gut connection. [Online] Available from: https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-brain-gut-connection [Accessed: 25th October 2021]
- Limbana T, Khan F, Eskander N. Gut microbiome and depression: how microbes affect the way we think. Cureus. [Online] 12(8): e9966. Available from: doi:10.7759/cureus.99663.
- The gut-brain connection. [Online] Harvard Health. Available from: https://www.health.harvard.edu/diseases-and-conditions/the-gut-brain-connection [Accessed: 25th October 2021]
- Pre and probiotics: what are they and how do they work? [infographic]. [Online] Atlas Biomed blog | Take control of your health with no-nonsense news on lifestyle, gut microbes and genetics. Available from: https://atlasbiomed.com/blog/what-are-pre-and-probiotics-which-foods-and-how-do-they-work/ [Accessed: 25th October 2021]
Imperial Bioscience Review 