The role of gut bacteria on mental health

Over the past few years, Atlantia Clinical Trials has been looking at how the gut microbiota influences brain function and how it can be targeted to improve mental health.

The average adult gut contains over a kilo of bacteria. Yet, the composition of that microbiota varies from person to person. Microbiota composition is almost as unique as an individual’s DNA profile or fingerprint, and there are many different factors that determine gut microbiota.

What determines microbiota?

Genetics play a significant role as they determine what bacteria can colonize the colon, but in terms of the initial microbiota, the main determinant is how we were born. If a baby is born per vaginum then the initial bacteria are acquired from the mother’s vagina. A baby born per vaginum will have a microbiome largely consisting of lactobacilli.

On the other hand, if a baby has been born by cesarean section, the initial bacteria that are acquired will be from the skin of the doctor, the nurse, the mom, and it’ll be a far more diverse microbiota than that of the baby born by cesarean section.

What impacts microbiota?

As we age, the microbiota alters, and it is now clear that loss of diversity of the microbiota due to aging actually precedes the onset of frailty, so we really want to maintain a diverse microbiota as we age.

The factors that can impact microbiota as we get older would be things such as stress. Stress can have quite a dramatic impact on the gut microbiota. Antibiotics will dramatically alter the gut microbiota, and indeed, many medications that are routinely prescribed in clinical practice can impact the gut microbiota. Two things that enable a more healthy microbiota relate to diet and exercise.

How do gut microbes influence the brain?

Gut microbes influence the brain in a number of different ways. The vagus nerve is the long meandering nerve that connects the brain and the gut, and signals travel from the gut to the brain and from the brain to the gut.

Certain microbes require an intact vagus nerve for brain-gut communication to take place. A number of years ago, it was shown that certain lactobacilli, for instance, could not transmit signals to the brain if the vagus nerve was severed.

Another important root of communication is the production of 5-HT and the 5-HT metabolite tryptophan. Tryptophan is the precursor 5-HT, and we know that the human brain requires a constant supply of tryptophan in order to maintain normal mood, sleep patterns and appetite. Certain bacteria, particularly bifidobacteria, can increase the levels of tryptophan in the plasma.

The production of short-chain fatty acid is also an important root of communication. The most extensively studied short-chain fatty acids are butyrate, propionate and acetate. They are produced by the metabolism of fiber in the intestine and they can have a profound impact on brain function.

Butyrate is an epigenetic modulator, specifically an HDAC inhibitor, so it can impact the way in which genes in the brain function. It also acts on classic G-protein-coupled receptors. There are two receptors, FFR2 and FFR3, and butyrate can act through those receptors.

For normal brain function, we require the production of various molecules by the gut microbiota as gut microbes produce molecules that we cannot produce ourselves, and our brains require some of these molecules. It is a synergistic interaction. Gut microbes are fed, and, in turn, they produce molecules that our brains require.

Common ways to alter gut microbiota

At present, we cannot change the genes in our cells, but there are ways in which we can change the genes in our microbiota. We can do this in a variety of ways, including diet and using drugs such as antibiotics.

Gut Microbiota can be altered with probiotics, which, in terms of the US regulatory authorities, are now referred to as live biotherapeutics. These include prebiotics, which are fibers that promote the growth of good bacteria and the more genital dietary way. However, a radical way of altering the gut microbiota is through fecal microbiota transplantation, which is used to treat conditions like C. difficile infection in the elderly.

Over 75% of the commonly prescribed drugs in clinical practice impact the gut microbiota, some in very dramatic ways. Proton-pump inhibitors are widely used for treating hyperacidity or peptic ulceration. They dramatically impact the gut microbiota, but so do many different drugs routinely prescribed in clinical practice.

Stress is another important driving factor for many psychiatric disorders like anxiety disorders and depression and irritable bowel syndrome. We can, however, alter stress responses by altering the gut microbiota, as shown in a study published by Atlantia Clinical Trials a few years ago.

Aside from stress, there are a number of other scenarios where the gut microbiota has been implicated, including disorders like schizophrenia and autism and various degenerative conditions such as Parkinson’s disease. Recently there have been suggestions that the gut microbiota may even be involved in addiction, particularly with regard to alcoholism.

A wide variety of conditions are associated with abnormalities of the gut microbiota. The concept of psychobiotics, which was introduced into the literature a few years ago, had a positive mental health benefit when ingested in adequate amounts. The concept of psychobiotics might even be beneficial in treating milder forms of depression or milder forms of anxiety.

Bacteria with psychobiotic activity

To support the concept of psychobiotics, a bif longum study was undertaken. It was given to mice and it was demonstrated that these mice were less anxious when they were taking bif longum. They also seemed to have enhanced cognitive function.

This study was then trialed in humans as a placebo control trial. The results concluded that when subjects were taking this bif longum they felt less stressed and their cortisol level in the morning was reduced. Not only were stress levels reduced, frontal mobility – a marker of anxiety – was altered upon ingestion of this particular bif longum.

When this probiotic was trailed with students, an improvement in sleep duration was seen as opposed to when they were taking the placebo. So it does seem to indicate that not only does this probiotic reduce anxiety levels, but it also improves sleep quality.

It is important to note that not all probiotics translate from animals to humans. This is a study of the most promising probiotic we worked with pre-clinically and it failed miserably in our studies in humans. We found no evidence whatsoever to indicate that it had any impact on any aspect of psychological functioning or any aspect of immune functioning.

Another probiotic study involved pregnant women who were given a probiotic or placebo for six months and followed up after the pregnancy. There were some limitations to the study, but it essentially demonstrated that the women who were taking the probiotic had less postpartum depression than the women who were not.

Summary

To conclude, gut microbiota is an appropriate target for intervention in relation to mental health. Atlantia Clinical Trials do clinical trials for the food and, to some extent, farm industry. Atlantia Clinical Trials designs trials for companies and does actual clinical trials on their behalf.

About Atlantia Clinical Trials

Atlantia Clinical Trials Ltd is a CRO that specializes in conducting studies in foods, beverages and supplements for companies world-wide that want to scientifically validate their functional ingredients to support an: EFSA (European Food Safety Authority) Health Claim; FDA (Food & Drug Administration) Structure Function Claim; or General Product Marketing Claim.

Atlantia works with world leading scientists (among the top cited 1% internationally, in the areas of digestive health and functional foods) at the: APC Microbiome Institute in University College Cork, Ireland; Teagasc, Moorepark, Ireland and recognized centers of excellence globally.

Atlantia runs and operates its own clinic sites and conducts all studies to ICH-GCP standard (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice). Its team includes physician experts in digestive health, mental health (psychological stress and cognition), cardiovascular health, sports performance, metabolic disease, bone health, immune health and healthy ageing. The clinical team also includes project managers, research nurses, nutritionists, certified sports trainers and lab researchers.

Atlantia manages all elements from protocol design, placebo manufacture, recruitment, and study execution, to sample and data analysis, statistics and report/dossier preparation to provide a service which is technically, scientifically and clinically superior.

The clinical studies cover a broad spectrum of functional food and beverage categories, such as dairy, cereal, probiotic, different protein forms, infant-specific foods, vitamins/minerals, plant or marine extracts and medical foods.


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Last updated: Feb 8, 2022 at 9:22 AM

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