Psychobiotics are helpful bacteria (probiotics) or support for these bacteria (prebiotics) that influence the relationship between bacteria and brain. The human digestive system houses around 100 trillion of these bacteria, outnumbering the human body cells 10:1. Probiotics provide a great deal of functions vital to our well-being, like supporting the digestion process and improving the absorption of nutrients. Based on the latest research, helpful gut bacteria that can also positively affect the brain – psychobiotics – benefit people suffering from chronic stress, poor mood, or anxiety-like symptoms (1).

There are 3 ways psychobiotics can affect your mental health:

  • Brain chemicals like serotonin, dopamine, and noradrenaline can be produced in the intestines directly by gut microbiota.
  • Battling with and protecting from stress by modifying the level of stress hormones.
  • When an inflammation occurs, inflammatory agents are elevated throughout the body and brain and can cause depression and other mood and cognitive disorders. Psychobiotics can affect the brain by lowering inflammation.

Lactobacillus and Bifidobacterium are the most popular probiotics with respect to mental health (1).

Disruption of the balance of gut bacteria is quite common due to the use of different kinds of medications, antibiotics, artificial preservatives, poor food and water quality, herbicides, stress, and infections (2, 3, 4).

In order to support a healthy microbiota, one should start from eating a diverse range of foods rich in different plant sources. Foods that contain lots of fiber or are fermented also promote the growth of beneficial gut bacteria. Excessive consumption of sugar and artificial sweeteners should be minimized. Managing stress levels, exercising on a regular basis, not smoking and getting enough sleep are also important for keeping microbiota in good condition. When taking antibiotics, one should make sure to consume probiotics so the body can maintain the bacteria it needs to stay healthy.

For people needing help regarding mental health problems, psychobiotics may be a promising relief. Psychobiotics are well-adapted to the intestinal environment and naturally modulate gut–brain axis communications, thereby reducing the chance of adverse reactions.

It is possible that even simple prescribing of a particular diet may be sufficient to promote the selective proliferation of natural or therapeutically introduced psychobiotics (5). Further research focusing on the strain and dosage of psychobiotics, duration of treatment, and the nature of mental disorders will help to determine the most efficient ways of helping people to improve their mental health.

REFERENCES
Abhari A, Hosseini H (2018) Psychobiotics: Next generation treatment for mental disorders? J Clin Nutr Diet. 4:1. doi:10.4172/2472-1921.100063

Carding et al (2015) Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 26: 10.3402/mehd.v26.26191

Lozano et al (2018) Sex-dependent impact of Roundup on the rat gut microbiome. Toxicol Rep. 5:96–107. doi: 10.1016/j.toxrep.2017.12.005

Paula Neto et al (2017) Effects of food additives on immune cells as contributors to body weight gain and immune-mediated metabolic dysregulation. Front Immunol. 8:1478. doi:10.3389/fimmu.2017.01478

Kali (2016) Psychobiotics: An emerging probiotic in psychiatric practice. Biomed J. 39(3):223-224. doi:10.1016/j.bj.2015.11.004

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Mediterranean diet could prevent depression, new study finds” [CNN]; “Mediterranean diet ‘may help prevent depression‘” [BBC]. The publication of Lassale and her colleagues in the prestigious scientific journal Molecular Psychiatry on the association between Mediterranean Diet and depression, received a lot of attention in the media last week.

So, can diet really influence your mental health? The publication of Lassale shows that there are indications that what you eat is related to how you feel. But because this study is an observational study, we can’t conclude anything yet about causation. In other words, we don’t know yet whether eating healthy causes you to feel less depressed, or whether feeling depressed causes you to eat unhealthy.

Causal links between diet and mental health

Diet and mental healthThe researchers of the European consortium Eat2beNICE are investigating exactly this causal link. The way we do this is through clinical trials. In this way, we first let chance decide whether a person receives a particular diet or is part of the control group. Through this randomization we can be sure that the differences that we find between the two groups are really due to the dietary intervention that people received, because all other factors are the same between the two groups.

Specifically for the effects of the Mediterranean diet on behaviour, in the Eat2beNICE project we are using the information and measurements available from the PREDIMED-PLUS trial. In this study, we are looking specifically for the effect of a calorie-restricted Mediterranean diet, combined with physical activity, on several behavioral outcomes related with several psychiatric diseases of adults at high cardiovascular risk.

At the same time, we are conducting three other clinical trials:

  1. In Nijmegen (The Netherlands), we investigate the effects of a very strict, hypo-allergenic diet on behavioural problems in children with ADHD.
  2. We are investigating the effects of vitamin supplements in a clinical trial that will be conducted in Mannheim(Germany) and Groningen(The Netherlands).
  3. Researchers in Barcelona (Spain) and Frankfurt (Germany) are investigating the effects of probiotics (i.e. bacteria that are good for you) on mental health in adults that are highly impulsive and/or aggressive.

Through these studies we hope to be able to identify if these types of food improve mental health and in which circumstances. This can have big implications for psychiatry, where putting someone on a specific, personalised diet may be a way to improve treatment. Also, people who are at a risk for developing mental health problems may benefit from specific diets to reduce this risk. But before this can be put into action, we first need good scientific data on what really works.

How can food drive human behaviour?

A second aim of our large research consortium is to identify the mechanisms between nutrition and the way the brain works. We think that the bacteria that live in your gut play a large role in this, as they interact with other systems in your body, including your brain. So we are collecting poop samples of the people that are participating in our clinical trials to identify which bacteria are more or less common in our participants compared to the control population. We are also measuring our participants’ behaviour and we will scan their brains. We hope that this will help us understanding better why certain types of food can be beneficial for mental health, and why some others increase the risk for mental health problems. This too will help to elucidate, and understand, the causal links between food and behaviour.

In short, we are very thankful for the study of Lassale and her colleagues, for backing up the evidence that what you eat is related to how you feel and behave. Now there’s work for us to do to prove the causal and mechanistic links. We’ll keep you posted here!

 

Authors Jeanette Mostert and Alejandro Arias-Vasquez work at the department of Genetics at the Radboud University Medical Center in Nijmegen, The Netherlands. Alejandro Arias-Vasquez is the project coordinator of the Eat2beNICE project. Jeanette Mostert is the dissemination manager.

 

Further reading

Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, Akbaraly T. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry. 2018 Sep 26. doi: 10.1038/s41380-018-0237-8.

 

Blog by Jordi Salas explaining the Lassale paper and the PREDIMED trial:
http://newbrainnutrition.com/category/nutrition/mediterranean-diet/

Blog by Jolanda van der Meer on hypo-allergenic diet (TRACE study): http://newbrainnutrition.com/adhd-and-food-elimination-diet/

Blog by Julia Rucklidge on trials with vitamin supplements: http://newbrainnutrition.com/micronutrients-and-mental-health/

Blog by Judit Cabana on the Gut-Brain axis: http://newbrainnutrition.com/the-gut-brain-axis-how-the-gut-relates-to-psychiatric-disorders/

 

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Recently, the idea that gastrointestinal microbiota are able to affect host behaviour is gaining momentum and it is based on studies conducted with animal models but also in humans with neurological disorders. However, the mechanisms that underlay this complex interplay between gut, brain and microbiota are not completely understood. Here we discuss recent findings on how microbial products could potentially affect the gut-brain axis.

Intestinal microbiota grow through the fermentation of undigested carbohydrates that end up in the large intestine. It was shown that absence of microbes or disruption of the microbiota, led to increased populations of impaired microglia cells in mice. Microglia cells are the primary effector cells for immune signalling to the central nervous system. The presence of a complex microbiota community, was shown to be essential for proper microglia maturation and function [1].

The main products of microbial fermentation in the gut are; acetate, propionate and butyrate, collectively known as short chain fatty acids(SCFA’s). Their beneficial role in human physiology have been well described, and recently evidence suggests that these molecules are able to cross blood brain barrier [2]. Moreover, gut microbiota have been associated with the brain barrier integrity. Mice raised in absence of bacteria are reported to have reduced brain barrier integrity. Once colonized with either a butyrate or an acetate/propionate producing bacteria, significant improvements were reported in the barrier [3]. Notably the integrity of the blood-brain barrier from the germ free mice was able to be restored through the oral administration of butyrate.

Gut_Microbes and Mental HealthSCFA’s are among the molecules having the privilege to cross the blood brain barrier and access the brain directly, their role should be studied in detail.

Recent studies also demonstrate that gut microbes regulate levels of intestinal neurotransmitters. The enteric nervous system interacts with a plethora of neurotransmitters (more than 30 have been identified so far.) Actually, the bulk of serotonin production ~90%, a neurotransmitter associated with mood and appetite is located in the gut. Specialized cells known as enterochromaffin cells are the main serotonin producers in the gut. In the absence of intestinal microbiota gastrointestinal serotonin levels are depleted. However, they can be restored by the addition of a specific spore forming consortium of intestinal bacteria. Specific bacterial metabolites have been reported to mediate this effect [4].

Other intestinal microbiota have been reported also to regulate the levels of the GABA neurotransmitter. Reduced levels of GABA have been associated with anxiety, panic disorder and depression. Bacterial GABA producers have been known to exist for years but it was not until 2016 that a gut bacteria was identified as GABA consumer [5]. For example, decreased levels of bacterial GABA producers were identified in a human cohort of depressed individuals. Studies in mice reinforce these findings. Intervention with the lactic acid bacteria Lactobacillus rhamnosus (JB-1) in healthy mice reduced anxiety related symptoms (accompanied by a reduction in the mRNA expression of GABA receptors in the Central Nervous System.) Lactic acid producing bacteria have also been reported to produce GABA in several food products such as kimchi, fermented fish and cheese [6].

Collectively, our gut microbiota encodes for ~100 times more genes than the human genome. The potential for some of these microbial genes to produce compounds able to interact with the nervous system and regulate critical pathways implicated in the gut brain axis is realistic and worth being explored.

Authors Prokopis Konstanti, MSc and Clara Belzer, PhD are working in the Department of Molecular Ecology, Laboratory of Microbiology, Wageningen University, Netherlands.

Footnotes

  1. Erny, D., et al., Host microbiota constantly control maturation and function of microglia in the CNS. Nature neuroscience, 2015. 18(7): p. 965-977.
  2. Joseph, J., et al., Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia? Frontiers in Neuroscience, 2017. 11(155).
  3. Braniste, V., et al., The gut microbiota influences blood-brain barrier permeability in mice. Science translational medicine, 2014. 6(263): p. 263ra158-263ra158.
  4. Yano, J.M., et al., Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 2015. 161(2): p. 264-276.
  5. P. Strandwitz, K.K., D. Dietrich, D. McDonald, T. Ramadhar, E. J. Stewart, R. Knight, J. Clardy, K. Lewis; , Gaba Modulating Bacteria of the Human Gut Microbiome. 2016.
  6. Dhakal, R., V.K. Bajpai, and K.-H. Baek, Production of gaba (γ – Aminobutyric acid) by microorganisms: a review. Brazilian Journal of Microbiology, 2012. 43(4): p. 1230-1241.

 

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As described in my previous blog post (Nutrition, Gut Microbiota and Behavior, 4th of April), I will investigate the association between nutrition, gut microbiota and behavior. One of the main focuses within my research is to investigate the association between early life nutrition, gut microbiota development and inhibitory control within toddlers and pubertal children.

The first 1000 days of life (starting from conception) were shown to be a critical window for child development. In this phase, nutritional intake of the infant can stimulate the body and brain towards a healthy development, also known as nutritional programming1. Hence, early life nutrition, i.e. breastfeeding, can exert a major influence on infant development and thus future behavior. Breast milk contains many beneficial components such as sugars, immune factors and bacteria which are difficult to process in bottle formulas. Thus, exclusive breastfeeding is recommended until six months of age in the Netherlands.breastfeeding and early nutrition

Several studies have looked at the association between infant breastfeeding duration and future executive functioning. (Executive functions are cognitive processes in the brain that contribute to regulating thoughts and behaviors. Executive functions can be roughly divided into three core functions, namely: inhibitory control, working memory, and cognitive flexibility. Inhibitory control, which can be interpreted as the opposite of impulsivity, is necessary to suppress impulses.) Two studies found positive associations with breastfeeding duration and executive functioning in childhood2,3. However, some studies have found no associations between infant breastfeeding and future executive functioning 4,5. These studies have examined general executive functioning and mainly focussed on attention, and not inhibitory control. Furthermore, different ages and populations were examined which makes it difficult to draw firm conclusions about the association between breastfeeding duration and future executive functioning. Thus, it is of particular interest whether inhibitory control is association with breastfeeding duration.

In addition, previous literature has focused mostly on duration of breastfeeding, while the composition of breast milk is also of major importance. Breastmilk contains many nutrients that are finely attuned to the needs of the infant. It contains biologically active compounds which have diverse roles, among others guiding the development of the infant’s intestinal microbiota6. Breast milk also contains specific sugars, also known as human oligosaccharides, which have been shown to influence the types of microbiota colonizing in the infant gut7. This may potentially be associated with impulsive behaviour8. Thus, in addition to examining breastfeeding duration in relation to inhibitory control, I will also examine the breastmilk composition in relation to inhibitory control.

  1. Agosti, M., Tandoi, F., Morlacchi, L. & Bossi, A. Nutritional and metabolic programming during the first thousand days of life. La Pediatr. Medica e Chir. 39, (2017).
  2. Hayatbakhsh, M. R., O’Callaghan, M. J., Bor, W., Williams, G. M. & Najman, J. M. Association of Breastfeeding and Adolescents’ Psychopathology: A Large Prospective Study. Breastfeed. Med. 7, 480–486 (2012).
  3. Julvez, J. et al. Attention behaviour and hyperactivity at age 4 and duration of breast-feeding. Acta Paediatr. 96, 842–847 (2007).
  4. Belfort, M. B. et al. Infant Breastfeeding Duration and Mid-Childhood Executive Function, Behavior, and Social-Emotional Development. J. Dev. Behav. Pediatr. 37, 43–52 (2016).
  5. Groen-Blokhuis, M. M. et al. A prospective study of the effects of breastfeeding and FADS2 polymorphisms on cognition and hyperactivity/attention problems. Am. J. Med. Genet. Part B Neuropsychiatr. Genet. 162, 457–465 (2013).
  6. Andreas, N. J., Kampmann, B. & Mehring Le-Doare, K. Human breast milk: A review on its composition and bioactivity. Early Hum. Dev. 91, 629–635 (2015).
  7. Lewis, Z. T. et al. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome 3, 13 (2015).

 

 

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The reason why I look at impulsive behavior is because mental disorders are the single largest contributors to disease burden in Europe. Impulsivity and compulsivity increase the risk of psychiatric disorders, especially Attention Deficit Hyperactivity Disorder, alcohol and drug abuse disorders, conduct disorder and antisocial disorders (including aggression). The urgency of addressing impulsivity and compulsivity is additionally strongly supported by the fact that these problems increase the risk for mortality.

My name is Yvonne Willemsen and I have started my PhD track at Radboud University in the Netherlands in October 2017. For my project I will assess the association between nutrition, gut microbiota composition and impulsive behavior in toddlers and young adolescents. In the following paragraphs, I will explain the first study that I am currently conducting.

Many previous studies have examined the association between nutrition and executive functions. Executive functions are cognitive processes in the brain that contribute to regulating thoughts and behaviors. Executive functions can be roughly divided into three core functions, namely: inhibitory control, working memory, and cognitive flexibility. Inhibitory control, which can be interpreted as the opposite of impulsivity, is necessary to suppress impulses. It is also an important core function of executive functions, as it supports working memory and cognitive flexibility.  To date, studies have examined the association between nutrition and executive functions in general (1). Whether nutrition is related to inhibitory control specifically (in toddlers and young adolescents) is something that still needs to be investigated.

The next step of my study is to understand how nutrition is associated with inhibitory control. To explain a possible mechanism, we will look at the gut microbiota. The reason why the gut microbiota is a point of interest is because gut microbiota can secrete molecules that may influence brain function, and thus may influence inhibitory control (2). This connection between the gut and the brain is also known as the gut-brain axis. Gut microbiota composition can change according to nutritional intake, and can therefore play a role in the gut brain axis (3). To assess the association between nutrition, gut microbiota and behavior in toddlers and young adolescents, we will use questionnaires and different behavioural measures.

  1. Cohen, J. F. W., Gorski, M. T., Gruber, S. A., Kurdziel, L. B. F. & Rimm, E. B. The effect of healthy dietary consumption on executive cognitive functioning in children and adolescents: a systematic review. Br. J. Nutr. 116, 989–1000 (2016). Link
  2. Rogers, G. B. et al. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol. Psychiatry 21, 738–748 (2016). Link
  3. Oriach, C. S., Robertson, R. C., Stanton, C., Cryan, J. F. & Dinan, T. G. Food for thought: The role of nutrition in the microbiota-gut–brain axis. Clin. Nutr. Exp. 6, 25–38 (2016). Link
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The human gut is colonized by microorganisms in a similar number as the cells of the human body.

“Microbiota” refers to these microorganisms, and it maintains a symbiotic relationship with the host, contributing to essential functions such as food digestion, energy harvest and storage, the function of the intestinal barrier, and the immune system and protection against pathogenic organisms. Prenatal and postnatal factors can alter the composition of the microbiota, such as stress and diet or the use of antibiotics (see image).

Prenatal and Postnatal factors influence gut-brain axis and mental healthFor instance, stress during pregnancy can alter the composition of vaginal microbiota, which affects the composition of the microbiota of the newborn and is related to gastrointestinal (GI) symptoms and allergic reactions. Interestingly, there is a bidirectional communication between the GI tract and the central nervous system (the gut-brain axis) that involves neuronal and metabolic pathways, immune and endocrine mechanisms. Changes in the composition of the microbiota can lead to altered development of the brain and increased risk of psychiatric and neurodevelopmental disorders, such as anxiety, depression and autism (see image).

Depression is one of the most recurrent stress-related disorders that highly impacts the quality of life. Fecal samples of patients with depression have a decreased microbial richness and diversity than controls. The use of probiotics have been shown to help with sad mood and negative thoughts, which may be a potential preventive strategy for depression.

Autism is characterized by impaired communication, poor social engagement and repetitive behaviours, with frequent GI symptoms. We know that the bacteria composition is more diverse in autistic individuals than in unaffected subjects.

For other psychiatric disorders, such as Attention deficit/hyperactivity disorder (ADHD) and Schizophrenia, there is indirect evidence for a role of the microbiota, but more studies are needed.

This connection between the gut and brain is two way communication, and is known as “The Gut-Brain Axis.”

Our knowledge of the impact of gut microbiota on brain function is growing fast, which may pave the way to possible applications for the treatment of psychiatric and neurodevelopmental disorders.

Authors Judit Cabana, Bru Cormand, and Noelia Fernandez Castillo are in the Department of Genetics, Microbiology & Statistics, University of Barcelona, Catalonia, Spain

More information can be found in: Felice VD, O’Mahony SM. The microbiome and disorders of the central nervous system. (2017) Pharmacol Biochem Behav. Sep;160:1-13.
https://www.ncbi.nlm.nih.gov/pubmed/28666895

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