Are we what we eat, or who we are?

Plastered across stores, buses, hoardings, the ubiquitous Yakult probiotics have taken the market by storm. Whether to seek a novel experience or to advance in the health game, people throng to the stands to indulge in these products. My mother bought them too, and my grandfather almost acknowledged he had a life-changing sensation ingesting it. However, this market phenomenon remained inexplicable to me.

Some time ago, as an initial foray into science non-fiction, I happened upon a book-10% Human by Alanna Colleen that shook my foundation. Tiny microbes which constitute 90% of our being, influence our health, and bizarrely enough, this includes our mental health. The human body is the most brilliant design; the cogs must work perfectly to achieve good health; thus, it should not be surprising that our gut influences our mood… after all we do feel an unmatched euphoria after a good meal. What is astonishing is the role of microbe colonies in the gut in maintaining good mental health.

In 1998, mice were administered with the bacteria Campylobacter jejuni orally to incite a reaction. Surprisingly, they developed characteristic anxious behaviour. Brain scans revealed that the neural centres which receive information from the vagus nerve were activated. The vagus nerve is the 10th cranial nerve; the longest and the most complicated nerve, running an extensive course, connecting the brain to various parts of the body-face, thorax as well as abdomen. However, what is interesting, is that it innervates a large portion of the digestive tract, controlling involuntary muscles in the gut. Thus, questions arose on whether the microbial colonies in the gut could possibly influence brain plasticity and development via the vagus nerve.

Three specific mice populations, namely, germ-free (GF), specific-pathogen free (SPF) and gnotobiotic mice were examined for differences in their gut microbiome and their influence on stress response. GF mice are grown in completely sterile environments devoid of any microbe colonies. SPF mice are exempted from certain defined pathogens. Gnotobiotics are unique populations colonized only by a specific population of eight microorganisms (the altered Schaedler flora), all derived from mice and cultured separately to raise a pure lineage with only those eight microorganisms flourishing in them. Alterations in the hypothalamic-pituitary-adrenal axis’ (HPA) response to stress was tied to their microbiome, hence producing the first definitive report of commensal microbes influencing stress response.

The gut-brain axis is a bidirectional pathway, both the nervous system and the gut influence each other’s activities. The vagus nerve stimulates the enteric nervous system in the gut to activate neurotransmitters like serotonin, GABA, acetylcholine etc., to modulate neurological responses in the brain. Incidentally, the autonomic nervous system affects immune response in the gut to create an environment for microbe colonies to thrive harmoniously with our bodies. Immune modulation is an extremely delicate balance that must be maintained. In the absence of such balance, inflammation becomes a major threat which can alter digestion and emotions, affecting mental health. The gut microbiota also produces a number of metabolites, e.g. monoamines like serotonin, norepinephrine, dopamine that regulate mood alterations, stress response, etc. Together inflammation and monoamine disruptions are the most prominent symptoms of stress-induced mental disorders like clinical depression.

When there is an imbalance in the gut microbiota (dysbiosis), our entire health system fails. The “monoamine depletion theory of depression” postulates that underlying decrease in monoamine concentration affects the pathophysiology of depression. Both selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) show antidepressant properties. These chemicals increase serotonin and norepinephrine levels in the brain to alleviate depressive symptoms. Gut dysbiosis has been related to disruptions in monoamine concentrations, commonly observed in clinically depressed patients.

Inflammation in the gut is mostly regulated by cytokines which are chemical messengers, like interleukins, tumour necrosis factor alpha, interferons, etc. Gut dysbiosis upregulates production of proinflammatory cytokines which promote inflammatory response while downregulating anti-inflammatory cytokines which protect against uncontrolled inflammation. Elevated proinflammatory cytokines like IL-1β, specifically, triggers the NLRP3 inflammasome pathway. Basically, this cytokine is a major player in the gut-immune-brain communication. When our body senses stress, IL-1β, amongst others, activate the NLRP3 inflammasome which is an immune sensor capable of identifying stress, danger, etc. and initiates metabolic cascades to restore homeostasis. Connections between gut dysbiosis-caused inflammation and depressive disorder fostered the “inflammation hypothesis of depression”. This states that major changes in gut microbiota due to dysbiosis can manifest as stress that activates the NLPR3 inflammasome pathway resulting in lesser availability of mood-regulating neurotransmitters and neuropeptides.

So, what do these probiotics do! They are a combination of live bacteria and yeast aiding in reviving and sustaining microbiome balance. Our gut microbiome has a tremendous role in maintaining our health. Continuously working to secrete metabolites and with their involvement in every bodily function- these little invisible creatures keep us happy or unhappy. Tiny changes in diet result in giant changes to our well-being.  Fortuitously, the path to our mental well-being does indeed traverse across the gut. Thus, a happy gut means a happy life.

References:

  1. The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health by Jeremy Appleton
  2. Normal gut microbiota modulates brain development and behaviour by Rochellys Diaz Heijtz, Shugui Wang, Farhana Anuar, Yu Qian, Britta Björkholm, Annika Samuelsson, Martin L Hibberd, Hans Forssberg, Sven Pettersson. PMID: 21282636, PMCID: PMC3041077, DOI: 10.1073/pnas.1010529108
  3. Gut microbiota and depression: Pathophysiology of depression: hypothalamic-pituitary-adrenal axis and microbiota-gut-brain axis by J M Lima-Ojeda 1, R Rupprecht 2, T C Baghai 3 PMID: 33136173, DOI: 10.1007/s00115-020-01029-1
  4. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice by Premysl Bercik 1, Emmanuel Denou, Josh Collins, Wendy Jackson, Jun Lu, Jennifer Jury, Yikang Deng, Patricia Blennerhassett, Joseph Macri, Kathy D McCoy, Elena F Verdu, Stephen M Collins PMID: 21683077, DOI: 10.1053/j.gastro.2011.04.052
  5. The microbiota‐inflammasome hypothesis of major depression. Inserra, A., Rogers, G.B., Licinio, J. and Wong, M.L., 2018.  Bioessays, 40(9), p.1800027.

Written by Sakura Koner, Master’s student at University of Calcutta.

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