You’ve probably heard of the gut-brain axis, but what does it mean?

Extreme emotions or stress are well known to cause bowel upsets. The expressions ‘gut-wrenching’, ‘worried sick’ and ‘butterflies in the stomach’ are in common parlance. The connection between our gut and our feelings is widely accepted but it might also influence our cognition as well. The gut is referred to as the ‘second brain’, but how could it be?

The marvellous gut

The intestine is a complex sensory organ with a huge surface area that, like the skin, faces the external environment. It has numerous ways in which it detects gut contents: neurons, endocrine cells and immune cells, and these detection systems are more extensive than in any other organ in the body. The enteric nervous, an enteric division of the autonomic nervous system, contains 10⁸ neurons. The gut endocrine system uses more than 20 identified hormones, and the gut has 70-80% of the body’s immune cells. All these enable absorption of nutrients but also protect against intrusion of harmful toxins and bacteria that may come along with food. (Furness 1999)

Gut microbiota

The human intestinal microbiota is one of the most densely populated microbial communities on earth. It contains around 150 times more genes that the human genome. It can be influenced by genetics, host physiology and host environment factors such as lifestyle, medications and of course, diet. Dietary fibre and whole grains are associated with increased microbial diversity and shifts can occur in as little as 24 hours after a dramatic change in dietary fibre intake. (Holscher 2017)

What is the gut-brain axis?

Essentially, the gut-brain axis describes the cross-talk between the gut and the brain, facilitated by the central and enteric nervous system. We now know the gut microbiota influence these interactions, and ultimately the way we think and feel. Gut bacteria can interact with intestinal cells and the enteric nervous system, but also on the central nervous system through both neuroendocrine and metabolic pathways. It is now common to see gut-brain axis referred to as the microbiota-gut-brain axis.

How does the gut microbiota affect the brain?

Production, expression and turnover of neurotransmitters
Protection of intestinal barrier
Modulation of gut sensory neurons
Bacterial metabolites
Mucosal immune regulation

Studies on rats have identified clear effects of microbiota on stress reactivity, anxiety and depression behaviours, memory and learning. Probiotics and prebiotics have been used successfully to normalise these behaviours. (Zagórska 2020)

How does the brain effect the gut microbiota?

Ateration in mucus and biofilm production
Alteration in motility
Alteration in intestinal permeability
Alteration in immune function

The brain influences the gut in several ways, using both neural and hormonal pathways. The gut microbiota also affects the same intestinal cells. Psychological stressors can influence the microbiota in as little as two hours. Stress has numerous adverse effects including altering the mucous layer, affecting intestinal motility and permeability, and immune response. It appears that ‘worrying yourself sick’ has some physiological foundation.

When things go wrong in the microbiota-gut-brain axis

Adverse composition and diversity of microbiota have been associated with several chronic diseases including colorectal cancer, metabolic, autoimmune and allergic diseases and neurological disorders (Dorelli 2021). Microbiota dysbiosis, or imbalance of the gut microflora, is implicated in nervous disorders such as anxiety and depression - even autism, which is characterised by specific alterations in microbiota.

Functional Gastrointestinal Disorders (FGID) with no known cause such as Irritable Bowel Syndrome (IBS), bloating, constipation and diarrhoea are highly associated with mood disorders. Irritable Bowel Syndrome is now proposed as a disorder of the microbiota-gut-brain axis, specifically of brain-gut function (rather than gut-brain function) (Carabotti, 2015).

The gut-brain axis in obesity

There is growing evidence that the gut microbiota plays a role in obesity. People with obesity have different and more adverse microbiota profiles compared to those who are not. There are numerous mechanisms through which microbiota may contribute to obesity, including by influencing insulin resistance, inflammation, fat deposition, metabolism regulation, adiposity, energy balance, appetite and food reward signalling. The potential for dietary interventions and faecal microbiota transplantation are being investigated as promising metabolic therapies for healthy weight (Torres-Fuentes, 2017).

The microbiome (the microbiota and their genes) may also help or hinder weight loss. In a small lifestyle intervention study, researchers identified 31 metagenomic functional features associated with weight loss responses, including the major finding that the ability of the microbiome to break down starches was increased in people who did not lose weight (making more energy available). In people who lost more weight, there were more genes that help bacteria grow faster, multiply, replicate and assemble cell walls (Diener 2021).

Diet and the microbiota

There is a lack of consensus about what a healthy microbiota should be and there are a multitude of factors at play. Individuals vary in their responses to dietary interventions and effects are hard to disentangle from broader lifestyle, diet and environmental factors. A review of the effects of diet on the microbiota found good support for probiotics and prebiotics, and promising effects for polyphenols. The microbiota is adversely affected in people who are alcoholic, but studies with alcohol in healthy people are mixed and may involve synergy between polyphenols, fibres and ethanol- more research is needed (Redondo-Useros 2020).

Sugars, sweeteners and the microbiota

There is scarce evidence from human studies evaluating effects of added sugars on the microbiota. Most describe lower bacteria diversity from diets that are generally characterised by energy-dense, nutrient-poor, highly processed foods with additives. There are adverse effects on the microbiota of large doses of alternative sweeteners in animal studies, but scant research in humans using realistic amounts within a habitual diet (Redondo-Useros 2020).

Probiotics

Probiotics, or live beneficial bacteria in food or supplements that confer benefit to the host, are a key therapeutic tool to improve the microbiota-gut-brain axis. There is potential for specific strains of bacteria to help with different conditions. For example, there is strong evidence for Lactobacillus reuteri for the treatment of infantile colic, and some evidence for Lactobacillus rhamnosus for the treatment of IBS (Hojsak 2019). Probiotics have been investigated for the treatment of psychiatric disorders and a new term ‘psychobiotics’ coined. Promising results have been found for depressive symptoms, although further evidence is required to identify strains, dosage, treatment duration and interactions (Zagórska, 2020).

Prebiotics

Prebiotics are the term given to the different types of dietary fibre that can enhance the activity of beneficial microbes, and thus confer benefit to the host. Not all dietary fibres are prebiotic- as they need to be fermentable by gut bacteria. Bacteria then produce short chain fatty acids (SCFA) that not only feed the microbiota but are also transported through the bloodstream to affect distant organs. Plant food rich diets can provide a variety of fibre types that support a diverse microbiota. (Holscher 2017).

Fermented foods

A review of 19 human intervention studies found promising results that fermented foods (such as kimchi, kefir) can positively modify gut microbiota however more studies are needed to confirm benefit (Stiesma, 2020).

Exercise

Exercise is thought to positively influence the gut microbiota-gut-brain axis. Microbes that produce Short Chain Fatty Acids (SCFA) may have a role in reducing neuroinflammation and mental fatigue, thus offering a mechanistic explanation for the protective benefit of exercise on mental wellbeing. A systematic review identified ten studies and most reported higher variability and prevalence of phylum firmicutes (healthy bacteria) in active people, especially athletes (Dorelli 2021).

Conclusion

A healthy and diverse microbiota appears to have many and broad benefits for both physical and mental wellbeing. A balanced and varied plant-based diet with plenty of dietary fibre types along with physical activity and psychological fitness are prudent for beneficial interplay between the gut and the brain.

 REFERENCES

• Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015 Apr-Jun;28(2):203-209. PMID: 25830558; PMCID: PMC4367209.
• Diener C, Qin S, Zhou Y et.al. Baseline Gut Metagenomic Functional Gene Signature Associated with Variable Weight Loss Responses following a Healthy Lifestyle Intervention in Humans. mSystems, 2021; DOI: 10.1128/mSystems.00964-21 (open access)
• Dorelli B, Gallè F, De Vito C, Duranti G et.al. Can Physical Activity Influence Human Gut Microbiota Composition Independently of Diet? A Systematic Review. Nutrients. 2021 May 31;13(6):1890. doi: 10.3390/nu13061890. PMID: 34072834; PMCID: PMC8228232.
• Furness JB, Kunze WAA, Clerc N. Nutrient tasting and signaling mechanisms in the gut II. The intestine as a sensory organ: neural, endocrine, and immune responses. Am J Physiology 1999; 277: G922-G928. doi/pdf/10.1152/ajpgi.1999.277.5.g922
• Hojsak I. Probiotics in Functional Gastrointestinal Disorders. Adv Exp Med Biol. 2019;1125:121-137. doi: 10.1007/5584_2018_321. PMID: 30578460.
• Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017 Mar 4;8(2):172-184. doi: 10.1080/19490976.2017.1290756. Epub 2017 Feb 6. PMID: 28165863; PMCID: PMC5390821.
• Redondo-Useros N, Nova E, González-Zancada N, Díaz LE, Gómez-Martínez S, Marcos A. Microbiota and Lifestyle: A Special Focus on Diet. Nutrients. 2020 Jun 15;12(6):1776. doi: 10.3390/nu12061776. PMID: 32549225; PMCID: PMC7353459.
• Stiemsma LT, Nakamura RE, Nguyen JG, Michels KB. Does Consumption of Fermented Foods Modify the Human Gut Microbiota? J Nutr. 2020 Jul 1;150(7):1680-1692. doi: 10.1093/jn/nxaa077. PMID: 32232406; PMCID: PMC7330458.
• Torres-Fuentes C, Schellekens H, Dinan TG, Cryan JF. The microbiota-gut-brain axis in obesity. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):747-756. doi: 10.1016/S2468-1253(17)30147-4. Epub 2017 Aug 24. PMID: 28844808.
• Zagórska A, Marcinkowska M, Jamrozik M, Wiśniowska B, Paśko P. From probiotics to psychobiotics - the gut-brain axis in psychiatric disorders. Benef Microbes. 2020 Dec 2;11(8):717-732. doi: 10.3920/BM2020.0063. Epub 2020 Nov 16. PMID: 33191776.