Biology and human biology in particular are proving to be the New World for scientific explorers in the twenty-first century. Human beings and multicellular life itself are incredibly complex – think of DNA and hierarchical complexity. Evolution has, over millions and billions of years, created amazing life forms bearing a rich fabric of nuanced workings. Who would have thought that the annals of gastroenterology would shed such a bright light on the delicate feelings and behaviours of us Homo Sapiens? The gut brain axis (GBA) is emerging as a prominent player in the way we experience life via our thoughts, feelings, and sensations. Science is revealing the important role that gut microbiota performs in bidirectional communication with the brain and its network of systems.

How Did We Discover the Gut Brain Axis?

It’s a little-known fact today that doctors throughout history, prior to the pharmacological revolution of the twentieth century, regularly studied the urine and stools of their patients in a bid to diagnose their state of health. This knowledge can be somewhat disturbing to those immured in the squeaky-clean visage of GPs doling out prescriptions for pharmaceutical drugs as cures for everything. Medicos using their senses to analyse the waste products of their patients seem positively anachronistic. However, the wheel is turning, and we’re returning to an understanding of the link between guts and minds in the twenty-first century. The gut brain axis: scientists foregrounding the #GutBrainAxis hashtag – is hot on the agenda in 2021.

In many ways new studies into the gut brain axis are a reflection of the shift from reductionist models in academia to an appreciation of more system-based learnings. Science has expanded its vision to incorporate an understanding of how seemingly separate bodily systems interact. The last couple of decades have seen research by microbiologists, neurologists, and nutrition scientists grow substantially. Their findings have radically transformed our understanding of how influential the GBA is on the emotional wellbeing of human beings (Miller, 2018).

Mice played a major role in many of the studies which showed the interconnectedness between gut microbiota and brain systems. Germ free (GF) mice, bred for the occasion, showed considerable differences in brain chemistry and responses to stresses in comparison to those mice with microbiota. A range of studies have observed the contribution of microbiome in modulating the GBA. These have involved probiotics, antibiotics, and infectious agents.

“In humans, the most compelling evidence of a gastrointestinal microbe-brain interaction arose more than 20 years ago from the observation of the often dramatic improvement in patients with hepatic encephalopathy, after the administration of oral antibiotics. In the meantime, emerging data support the role of microbiota in influencing anxiety and depressive-like behaviors and, more recently, of dysbiosis in autism. In fact, autistic patients present specific microbiota alterations according to the severity of the disease.” (Carabatti, 2015)

Mood, Food & The Psychobiotic Revolution

The gut brain axis has become hot property in psychiatric circles, with lively discussion and speculation foregrounding a psychobiotic revolution. This excitement revolves around the ingestion of live microorganisms as an alternative treatment for some mental health conditions. There has long been a global concern at the rising prevalence of depression and the related dependence upon pharmacological antidepressants in western societies. Psychobiotics are live bacteria (probiotics), which, when ingested in adequate quantities, can, via the GBA, deliver positive wellbeing outcomes. The definition of psychobiotics has been expanded recently to include prebiotics, which enhance the growth of good gut bacteria (Sarkar, 2016).

“In contrast to researchers in cancer and heart disease who have sought cures and preventions, biological psychiatrists in both academia and industry have set their sights on incremental and marketable advances, such as drugs with fewer adverse effects.” (Insel, 2006)

It has been posited that probiotics are, in effect, delivery vehicles for neurochemicals. For instance:

Escherichia, Bacillus, and Saccharomyces can produce Norepinephrine.

Streptococcus, Escherichia, and Enterococcus can produce Serotonin.

Bacillus and Serratia can produce Dopamine. (Roschina, 2010)

Bacteria can also modulate neurotransmitters in the human body.

Lactobacillus acidophilus can modulate the expression of cannabinoid receptors in the spinal cord.

Bif. Infantis can increase plasma tryptophan levels and modulate 5HT.

Lactobacillus rhamnosus alters central GABA receptor expression.

A review in Biological Psychiatry 2013, Psychobiotics: A Novel Class of Psychotropic stated that “as a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which acts on the brain-gut axis.” (Dinan, 2013)

Thus, certain psychobiotics contain antidepressant rendering qualities and have been successfully used and studied in psychiatric settings, especially in patients with irritable bowel syndrome (IBS).

Depression is an inflammatory disease and diet is a major cause of inflammation in human beings (Jacka, 2015). Diet changes were responsible for 57% of the total structural variation in gut microbiota in contrast to genetic mutation being only 12% (Zhang, 2010).

How Does the Gut Brain Axis Work?

The gut has recently been called the body’s ‘second brain’ (Hadhazy, 2010). New thinking sees the holistic paradigm revealing the interconnectedness of all things. However, many older forms of medicine have always understood this wider perspective on human health. Science has confirmed the bidirectional communication between the “central and the enteric nervous system, linking emotional and cognitive centres of the brain with peripheral intestinal functions.” (Carabotti, 2016)

There are signals going back and forth via neural, endocrine, immune, and humoral connections within our bodies. Nothing functions alone, it is a beautiful sea of influence. Researchers in this field use terms like ‘gut-brain crosstalk’ to reveal the complex nature of the interactive communication occurring. The information streams are flashing up and down our spinal cords, involving the autonomic and enteric nervous systems. The GBA is involving both the sympathetic and parasympathetic limbs of the autonomic nervous system. Thus, including both afferent and efferent neural signals to and from the gut and brain. Our brains are involved via the hypothalamic pituitary adrenal (HPA) axis. Signals are transmitted through enteric, spinal, and vagal pathways. These involve the limbic system, which is predominantly concerned with memory and emotional responses. Stress hormones like cortisol play a major role in dealing with environmental stress and how the brain/body functions in this regard. We now know that “both neural and hormonal lines of communication combine to allow the brain to influence the activities of intestinal functional effector cells, such as immune cells, epithelial cells, enteric neurons, smooth muscle cells, interstitial cells of Cajal and enterochromaffin cells. These same cells, on the other hand, are under the influence of the gut microbiota whose contributing role in brain-gut reciprocal communications has recently been assessed.” (Carabotti, 2016)

There are around 100 billion neurons in the human brain.

While there are 500 million neurons in the gut connected to the brain via the nervous system.

The vagus (wanderer in Greek) nerve travels throughout the human body. It is the largest nerve in the body and links many different systems and organs, including the cardiovascular, digestive, and reproductive systems. The vagus nerve travels from the brainstem down. Our vagus nerve takes readings from our gut microbiota. It then releases anxiogenic (anxiety increasing) and anxiolytic (anxiety reducing) reactions within our body/brain. We need to have good vagal tone to effectively deal with stress and poor tone has been linked to sufferers of irritable bowel syndrome (IBS).

“The system is way too complicated to have evolved only to make sure things move out of your colon,” says Emeran Mayer, professor of physiology, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles (U.C.L.A.). For example, scientists were shocked to learn that about 90 percent of the fibres in the primary visceral nerve, the vagus, carry information from the gut to the brain and not the other way around.” (Hadhazy, 2010)

The Gut Brain Axis is a Hot Topic in Scientific Circles

Our immune system development has been adversely altered by our reduced exposure to the microbes in our environment due to urban lifestyles and the preponderance of antibiotic usage and antibacterial cleaning agents in western cities (Toy, 2021). Our microbiome is established in the first few years of our life and is responsible for instructing our metabolism, immune system, and is involved in programming the brain. Interaction with the natural world, other humans, and animals is essential for the optimal development of gut microbiota. Scientists have clearly pointed the finger at the rising tide of chronic health conditions like asthma, depression, food allergies, diabetes, obesity, chronic fatigue syndrome, and such as being linked to issues with human microbiome. Bad diets due to eating high volumes of processed foods with little fibre are a major factor in poor microbiome diversity in modern human beings. A few facts to consider:

Antibiotic usage reduces microbiome diversity.

Diets rich in plant diversity produce greater microbiome diversity.

Microbiome diversity is better for your health.

There are companies marketing their microbiome analysis services to the general public in countries like Australia, the United States, China and the United Kingdom. The GBA is a fast-growing wellbeing concept, which is being readily embraced by those wishing to optimise their understanding of their body’s health. Consumers receive a detailed report, which promises to provide a personalised picture of their microbiome, with recommendations and comparisons.

The gut brain axis is illuminating a wide diversity of health challenges facing human beings in the modern world. Medical scientists across the globe are studying with relish the influence of our gut microbiota upon diseases, disorders, and the human condition. We are so much more than we first thought. We have spent the last century and a half quarantining ourselves and our families from germs thought to be bad for our health. We were only half right about that and have now discovered that we have cut ourselves off from a lot of good bacteria. Our immune systems need to be exposed to these microbes to develop healthy responses to stressors. The gut brain axis shows us that we can apply remedial dietary and probiotic and prebiotic treatments to realign our microbiome diversity. Eat more fibre and plant diversity to improve microbiome diversity. The more diversity in your gut microbiota the healthier you will be and less likely to suffer from disease. The gut-brain-axis-awareness is like having a new lever with which to meet the challenges of ageing and living a good life.

Sudha Hamilton is a natural health writer, historian, and chef. His published titles include: House Therapy: Discover Who You Really Are At Home; Healing Our Wellbeing; and Sacred Chef.

 

REFERENCES

 

Anderson. S, The Psychobiotic Revolution, Published: 26th December 2019, ISBN: 9781426219641

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Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28(2):203-209.

Dinan. T, Microbiome, Brain and Behaviour, National Genome Research Institute, 2013, watched on video on YouTube April 2021.

Hadhazy. A, Think Twice: How the Gut’s “Second Brain” Influences Mood and Well-Being, Scientific American, February 2010.

Insel. T, Scolnick, E. Cure therapeutics and strategic prevention: raising the bar for mental health research. Mol Psychiatry 11, 11–17 (2006).https://doi.org/10.1038/sj.mp.4001777

Jacka. F, Cherbuin, Anstey, Butterworth. Dietary Patters and Depressive Symptoms over Time: Examining the relationships with Socioeconomic Position, Health Behaviours and Cardiovascular Risk, BMC Med. 2015.

Lowry. C, The Microbiome and Mental Health, Brain & Behaviour Research Foundation, 2017, watched on video on YouTube April 2021.

Miller I. The gut-brain axis: historical reflections. Microb Ecol Health Dis. 2018;29(1):1542921. Published 2018 Nov 8. doi:10.1080/16512235.2018.1542921

Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PWJ. Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals. Trends Neurosci. 2016;39(11):763-781. doi:10.1016/j.tins.2016.09.002

Toy. S, Modern Life is Messing with Our Microbiomes, But Science is Fighting back, The Wall Street Journal, 11 March 2021.

Zhang C, Zhang M, Wang S, Han R, Cao Y, Hua W, Mao Y, Zhang X, Pang X, Wei C, Zhao G, Chen Y, Zhao L. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 2010 Feb;4(2):232-41. doi: 10.1038/ismej.2009.112. Epub 2009 Oct 29. Erratum in: ISME J. 2010 Feb;4(2):312-3. PMID: 19865183.