Yakult endorses one health system connecting gut microbiota to mental health

23 Oct 2023 --- Yakult Europe hosted thought leaders to present emerging research findings on the link between gut health and its effect on mental health. In the last 30 years, there has been a steep upward trend in rising cases of depression and anxiety in Western countries. Researchers have connected the upward trend and the gut microbiome’s role in preventing these mental and mood disorders to avoid “catastrophic collapse.”

Short-chain fatty acids (SCFA), which are microbial metabolites, as well as the probiotic Bifidobacterium longum (B. longum) NCC 3001 strain, were shown to have an impact on these kind of disorders.

“In our lab, we mainly focus on SCFA — acetic acid, propionic acid and butyric acid. These are the main actors in the colon and major metabolites that are produced from bacterial fermentation of dietary fiber and to a lesser extent from fermentation of proteins,” Kristin Verbeke, professor at the Translational Research Center in Gastrointestinal Disorders (TARGID) at the department of chronic diseases and metabolism, faculty of medicine, KU Leuven, tells the symposium audience, attended by Nutrition Insight.

“Most of what we know about the effect of SCFA on the brain we know from in vitro studies on animals and we are only beginning to understand how the composition and function of the microbiome influences diseases and mental health in humans.”

Old friends microbiota
Putting the situation in perspective, Dr. Olaf Larsen, senior manager of the science team at Yakult Netherlands and professor in One Health Innovation at Athena Institute, Vrije Universiteit Amsterdam, explains the rise of autoimmune diseases and the burgeoning need to address it at the root. 

“In the second half of the 20th century, crowd infections (measles, mumps, tuberculosis) were going down dramatically. This is not so surprising and can be linked to improved hygiene standards and more vaccines at the time. In parallel, autoimmune diseases were heavily on the rise,” says Larsen.

Today, scientists know that exposure to beneficial microbes called “old friends” trains the immune system to exhibit a proportional response to all kinds of components. Hence, a diminished exposure to these old friends may lead to health consequences in later life. 

An illustration of the compounds needed for a healthy gut (Graphic credit: Yakult).

“If you have trained your immune system, a later exposure to self-antigens will not lead to an excessive reaction to your immune system, which is typical for autoimmune type disorders, but also the exposure to all kinds of allergens will be dampened because of the initial exposure to ‘old friends,’” explains Larsen.

The researchers were interested to know whether the upward trends concerning the incidence of autoimmune disease, indicative for a diminished exposure to old friends, are also continuing in the 21st century. continues. “We were able to show that these trends do continue. Data on the incidences of multiple sclerosis and type-1 diabetes from Western European countries such as Finland, France, Germany, Italy, the Netherlands, the UK and the US indicate this.”   

Eurostat data shows that in 2019, before COVID, at least one in 14 European people suffered from chronic depression and the number kept rising. “For 30 years, it was really progressing. It is also known nowadays that the susceptibility to these types of diseases — but also the progression — whether it’s a mild or severe form of the disease is very intimately related to the quality of the gut microbiome and the gut microbiome is influenced by numerous factors such as typical delivery or cesarean section, exposure to animals, soil and so on,” Larsen continues. 

“Striving for a high microbiota diversity is essential. We see the microbial repertoire from generation to generation going down and ultimately, there’s no backup anymore, and then you start losing functionalities. That’s what we call a ‘catastrophic collapse.’ The ultimate goal is to prevent these catastrophic collapses by living in a one-health system,” Larsen explains.

Mental health mechanisms
Common thinking about food is that it provides energy and is a building material for the body. 

“Its ability to prevent and protect against mental diseases is only starting to be recognized and we think the gut microbiome plays a critical role in that,” notes Verbeke.

“It’s clear, of course, that the connection between physical and mental well-being is nuanced, complex and intricate, but little by little, we start gaining insight into how the brain and the microbiota community in our gut communicate.”

SCFAs have been identified as pivotal to the mechanisms that can improve mental health. These fatty acids enter the circulation system and can affect the liver, pancreas, brain and adipocytes.

“Daily production amounts to 500 mmol and we think that connects the diet, the microbiome and the host. This can already be considered as a health benefit. They are responsible for the pH drop in the proximal colon because it leads to inactivation of proteases — enzymes that ferment proteins in the large intestine — and inactivation of enzymes leads to a lesser degree of protein fermentation,” Verbeke explains.

In addition, the low pH inactivates many pathogens, such as salmonella, protecting people against infections from pathogens.

SCFA affects the brain via several pathways. The pathways of communication between the gut (microbes) and the brain comprise are, roughly,  the immune system, the vagus nerve and hormones (endocrine system). “At the moment, we do not know if all these pathways are also important in humans. This still needs to be investigated, but at least we have a hypothesis of how it could work,” Verbeke says. 

Stress response is an essential psychobiological function that underlies the development of several mental disorders, such as depression, mood disorders or anxiety.Short-chain fatty acids can improve gut health and reduce signs of depression and anxiety as they move via several pathways to the brain. 

“How our body reacts to the intensity of the stress response, duration and recovery may play a critical role in the development of gastrointestinal disorders, cardiovascular diseases and mental disorders,” explains Verbeke.

A well trained immune system, with sufficient exposure to old friends, will react with an inflammatory reaction to a stress response that is in accordance with the intensity of the psychosocial stressor being experienced. Without the training by old friends, an exaggerated inflammatory reaction, which is more intense and prolongs longer, and is not in proportion anymore to the external stressor. 

Strengthening symbiotic connections
Premysl Bercik, professor of internal medicine and gastroenterology, at McMaster University, revealed that the probiotic B. longum NCC 3001 benefits mental health. In one study, a six-week treatment of B. longum improved depression scores in 77% of patients compared with 35% placebo.  

The metabolite, 4-cresol sulfate, has been identified as capable of inhibiting the conversion from dopamine to norepinephrine. Dopamine is a key neurotransmitter in mammals, which is transformed into norepinephrine, a key neurotransmitter involved in depression and anxiety.

“The beneficial effect was not immune-mediated but dependent on the integrity of the vagus nerve. It is a metabolite secreted by the probiotic NCC3001 responsible for the benefits up until a month after administration of the probiotic being stopped,” Bercik says. 

In summary, gut microbiota affect the function and structure of the central and enteric neural systems. Gut bacteria communicate with the brain through the immune, neural and metabolic pathways and are different during individual stages of life. The altered structure and function of gut microbiota have detrimental effects on the host’s behavior and some probiotics may be beneficial for patients with mental health issues. 

In addition, research into the gut microbiome’s role in health continues to advance. US-based scientists at Harvard Medical School found a link between suppressing emotions and gut health among women but found no association with diets. 

By Inga de Jong