By Dr. David Vauzour 

The health of your gut, and the balance of the bacteria and other microbes that make up your gut’s microbiome, are increasingly being associated with playing a role in memory, learning, anxiety, stress, brain growth and potential protection against neuro-degenerative disorders including dementia.

This superhighway called the gut microbiota- -brain axis, is one of the hottest fields of research with as many as 30 new studies published every day!

Consequently, attention is now turning to how the microbiota can become the target of nutritional and therapeutic strategies for improved brain health and well-being. However, while such strategies that target the gut microbiota to influence brain health and function are currently under development with varying levels of success, still very little is yet known about the triggers and mechanisms underlying the gut microbiota’s apparent influence on cognitive or brain function.

How does your gut health affect your brain?

Much of the excitement comes from studies of specific bacteria that appears to be associated with improving memory [7], learning [7], stress resilience [8], and mood [6, 9, 10]—and even neurodevelopmental [11, 12] and neurodegenerative disorders [2]. 

But the big burning question is how? How does the gut microbiota influence brain development [13] and function [14]? Are brain disorders potentially shaped by the gut microbiota [15]? What role does diet play and what is its scope in influencing the gut microbiota–brain axis [16, 17]? How do dietary supplements exert their apparent effect(s) on stress, mood, and cognition [18, 19]? What physiological mechanisms are at play [20]? And do alterations in gut microbiota–brain interactions through life reflect the cause or symptom of an underlying brain condition [21]? 

The normal route of scientific discovery is first finding an association – that a particular dietary component is associated with, for example, better memory. Then, the question is how – what is the mechanism that can explain the effect?  Then, if possible, randomised placebo-controlled trials drill down to prove an effect. But it isn’t always easy to do this kind of linear research when many dietary factors may be involved, and the effects might take some time to occur.

The two-way street between gut and brain

A ‘gut feeling’ or the sensation of ‘butterflies’ in the stomach are common illustrations of how a response in the brain is felt in the gut. Meanwhile, what happens in the gut affects many aspects of health. The gut microbiota has a myriad of functions including education of the immune system, protection against pathogens, energy balance and metabolite production. What you eat is a key determinant of composition of your gut microbial populations, also impacting the time it takes for food to pass through the gut, which is largely a function of the fibre content of your diet. The fibre also slows down the release of sugars, which bacteria use to nourish themselves and multiply. As a result, they also produce short-chain fatty acids or SCFAs (see below). This then changes the gut’s environmental conditions, and critically determines the supply of substrates for microbial growth [22, 23]. Therefore, gut microbiota has the potential to be both a mediator of the effect of diet, for example, by reducing the body’s sugar load through its own consumption of slow-releasing sugar found, for example, in whole fruit rich in fibre but not fruit juices where the most of the fibre has been removed.

But the gut microbiome also changes the body’s digestive and metabolic response to diet. Thus, the effect of diet on metabolism depends on the microbiota but the effect is not due to diet-induced changes in the microbiota. Thus, the gut microbiota is modifiable by diet and specific dietary components, and it plays a key role in shaping the composition and activity of the microbiota from birth, which impacts lifelong health [24–27].

Your immune system starts in the gut

There are more immune cells in your gut than the whole of the rest of your body. The gut is, after all, your ‘inner skin’ the barrier between the outside and inside world of your body. The immune system functions as the bouncers, checking out everything you eat. When the immune system is out of whack, chronic low-grade inflammation develops. Low grade inflammation is found in most neurological conditions, including autism spectrum disorders (ASD), epilepsy, Alzheimer’s disease, Parkinson’s disease and cerebrovascular diseases such as strokes [32]. Gut bacteria also produce SCFAs such as butyric acid which helps protect the integrity of the gut wall and the blood-brain barrier (BBB) [52]. A progressively leaky BBB is being reported in Alzheimer’s disease [15]. 

Hormones and neurotransmitters are made in the gut

Critical hormones and neurotransmitters, the chemical messengers of the body, are made in the gut as well as the brain. Three critical messengers that affect the brain are dopamine, which is key to the ‘reward’ system of the brain, linked to addiction and is also the precursor for adrenalin; serotonin often called the mood hormone and GABA, which switches off adrenal stress hormone response and is believed to have a role in behaviour, cognition and the body’s response to stress, anxiety and fear [40]. Low GABA levels are associated with psychiatric illnesses, including schizophrenia, autism and depression [41]. GABA is also produced by some Lactobacilli [43] and specific strains of Bifidobacterium [13, 44]. 

Serotonin is involved in mood, cognition, sleep, and appetite control [46]. It is estimated that 90 percent of the body’s serotonin is made in the digestive tract and that gut microbiota may influence tryptophan uptake, the amino acid that serotonin is made from, and, in that way, serotonin synthesis [47].

Your gut microbiome is key to early-life brain health programming

Research has established many links, associations, and hypotheses about the lifelong influence of the gut microbiota on brain health. Underlining this critical role, one review ranks the gut microbiota as the fourth key factor in early-life programming of brain health and disease, alongside prenatal and postnatal environment, and host genetics [64]. The scientific challenge is to identify opportunities to alter and fine-tune the microbiota and, through that, enhance human health and well-being. Many scientists now believe in the close relationship between microbial diversity and healthy ageing. Studies in mice have shown that faecal microbiota transplantation can correct age-related defects in immune function [33]—and that a similar transplant from aged to young mice has a detrimental impact on key functions of the central nervous system [79, 80]. These and other findings highlight the importance of the gut microbiota–brain axis during ageing and raise the possibility that a ‘young’ microbiota may maintain or improve cognitive functions in life’s later years [81, 82]. Neurological research suggests the microbiota also play a role in neurodegenerative diseases [83]. This supports the idea that an ageing gut microbiota could be linked to immune and neuronal dysfunction in Alzheimer’s disease. 

What is a healthy microbiome?

While great advances are being made this field is in its infancy. The definition, that is the characteristics and function of a ‘healthy’ gut microbiota are still unknown. Generally, studies have found less diversity associated with more health disorders [61].  As yet there is little understanding of how the microbiota changes over time and may reflect the impending onset of disease. Recent data from more than 9000 adults of different ages show that, as individuals age, the gut microbiome becomes increasingly unique, increasingly different from others, starting in mid-to-late adulthood. 

Are probiotic supplements a daily essential?

Several systematic reviews and meta-analyses, albeit with different search criteria, have investigated the effects of probiotic (live friendly bacteria) and prebiotic (nutrients that feed bacteria) supplements, and even fermented foods on symptoms of depression, anxiety, and mood, as well as on cognition. Interestingly, while the majority of studies did conclude there were some positive effects of dietary interventions or supplements on depression and anxiety symptoms [18, 19, 70, 92], others concluded that the data to support the role of dietary interventions on mood and cognitive function were insignificant [93, 94]. It is therefore not possible to conclude that a daily probiotic supplement is a brain health essential. Many studies are underway, and we’ll keep you informed as to what they mean for you in terms of diet and probiotic supplementation.

Diet for your microbiome-gut-brain axis

However, eating whole foods rich in fibre and soluble fibres, such as oats and oatcakes, beans, nuts, seeds, whole fruit and vegetables is consistent with the scientific evidence. The integrity of the gut barrier is negatively affected by alcohol, gliadin in wheat, and lack of antioxidants and anti-inflammatory omega-3 fats which influence the microbiota[DV(S1]  so drinking less alcohol, eating less wheat, more fresh fruit, vegetables, herbs, spices and omega-3 rich seafood and plant food such as walnuts, chia or flax seeds is likely to be good for your microbiome and your brain.

Dr. David Vauzour is Senior Research Fellow and Principal Investigator at Norwich Medical School at the University of East Anglia, UK. He completed his PhD in Chemical and Biological Sciences for Health, Faculty of Pharmacy at the University of Montpellier in France. His research interests concern novel dietary or therapeutic strategies to delay brain ageing, cognitive decline and cardiovascular disease, including stroke and vascular dementia and involves the fields of oxidative stress, free radical biochemistry, neurodegeneration and the health effects of dietary polyphenols, as well as the role and impact of the microbiota and the microbiome-gut-brain axis on mental health.

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References and Further Reading

This article is adapted from A.Chakrabarti et al’s paper entitled  ‘The microbiota–gut–brain axis: pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice’. Cellular and Molecular Life Sciences (2022) 79:80, co-authored with Dr David Vauzour
https://doi.org/10.1007/s00018-021-04060-w.

The reference numbers given are those found in this research paper, downloadable at https://link.springer.com/article/10.1007/s00018-021-04060-w