Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated prevalence rate of 5.3% among children and of about 2.5% among adults. It is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity, being associated with significant impairment of social, academic, and occupational functioning across the lifespan.

However, despite many efforts, the exact etiology of ADHD still remains unknown and data about modificable risk and protective factors are largely lacking. Recent evidence has suggested an association between inflammation, immunological disturbances and ADHD. Supporting this idea, an increased incidence of immune-mediated disorders (e.g. asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, psoriasis, thyrotoxicosis or type 1 diabetes) accompanied by elevated serum/plasma and cerebrospinal levels of inflammatory markers (especially interleukin (IL)-6) or auto-antibody levels (e.g. antibasal ganglia antibodies, antibodies against the dopamine transporter) have been found in these patients.

Importantly, recent studies have shown the gut flora as an important immunoregulator (1-3) and it is hypothesized that an imbalance in the gut microbiota (dysbiosis) may have a negative effect on cerebral development and behavior (4). About 95% of all circulating serotonin, dopamine or noradrenaline precursors are produced by our gut microbiota, being this ‘enteric nervous system’ bidirectional connected to the central nervous system through hormonal or immune/inflammatory pathways.

In line with this, recent findings suggest that some aliments as probiotics can not only revert dysbiosis, but also modulate brain neurodevelopment, activity and improve cognition, mood and behavior due to their immunoregulatory and anti-inflammatory properties (5-7).

Therefore, understanding the microbiota and how the gut connects to the brain would be important both for the better comprehension of the biological bases that underlie some psychiatric disorders such as ADHD, as for the future development of new evidenced-based drugs for these conditions.

This was co-authored by Josep Antoni Ramos-Quiroga, MD PhD psychiatrist and Head of Department of Psychiatry at Hospital Universitari Vall d’Hebron in Barcelona, Spain. He is also professor at Universitat Autònoma de Barcelona.

REFERENCES:

1. Felix KM, Tahsin S, Wu HJ. Host-microbiota interplay in mediating immune disorders. Ann N Y Acad Sci. 2018; 1417(1):57-70.

2. Yadav SK, Boppana S, Ito N, Mindur JE, Mathay MT, Patel A, et al. Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood. Proc Natl Acad Sci U S A.2017; 114(44): E9318-27.

3. Mandl T, Marsal J, Olsson P, Ohlsson B, Andreasson K. Severe intestinal dysbiosis is prevalent in primary Sjögren’s syndrome and is associated with systemic disease activity. Arthritis Res Ther.2017;19(1):237.

4. Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016; 21(6):738-48.

5. Slykerman RF, Kang J, Van Zyl N, Barthow C, Wickens K, Stanley T, et al. Effect of early probiotic supplementation on childhood cognition, behavior and mood. A randomized, placebo-controlled trial. Acta Paediatr.2018; 107(12):2172-78.

6. Kane L, Kinzel J. The effects of probiotics on mood and emotion. JAAPA. 2018; 31(5):1-3.

7. Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci.2011;12(8):453-66

 

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Our body is colonized by trillions of microorganisms that are important for vital processes. Gut microbiota are the microorganisms living in the intestinal gut and play an essential role in digestion, vitamin synthesis and metabolism, among others. The mouth and the large intestine contain the vast majority of gut microbiota whether the stomach only contains few thousands of microorganisms, especially due to the acidity of its fluids. Microbiota composition is constantly changing, affecting the well-being and health of the individual.

Each individual has a unique microbiota composition, and it depends on several factors including diet, diseases, medication and also the genetics of the individual (host) (Figure). Some medicines, especially antibiotics, reduce bacterial diversity. Strong and broad spectrum antibiotics can have longer effects on gut microbiota, some of them up to several years. Genetic variation of an individual also affects the microbiota composition, and the abundance of certain microorganisms is partly genetically determined by the host.

The main contributor to gut microbiota diversity is diet, accounting for 57% of variation. Several studies have demonstrated that diet’s composition has a direct impact on gut microbiota. For example, an study performed on mice showed that “Western diet” (high-fat and sugar diet), alters the composition of microbiota in just one day! On the other hand, vegetarian and calorie restricted diet can also have an effect on gut microbiota composition.

Prebiotics and probiotics are diet strategies more used to control and reestablish the gut microbiota and improve the individual’s health. Probiotics are non-pathogenic microorganisms used as food ingredients (e.g. lactobacillus present in yoghurt) and prebiotics are indigestible food material (e.g. fibers in raw garlic, asparagus and onions), which are nutrients to increase the growth of beneficial microorganisms.

In the last years the new term psychobiotics has been introduced to define live bacteria with beneficial effects on mental health. Psychobiotics are of particular interest for improving the symptomatology of psychiatric disorders and recent preclinical trials have show promising results, particularly in stress, anxiety and depression.

Overall, these approaches are appealing because they can be introduced in food and drink and therefore provide a relatively non-invasive method of manipulating the microbiota.

AUTHORS:
Judit Cabana-Domínguez and Noèlia Fernàndez-Castillo

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Maladaptive or uncontrolled impulsivity and compulsivity lead to emotional and social maladjustment, e.g. addiction and crime, and underlie psychiatric disorders. Recently, alterations in microbiota composition have shown to have implications for brain and social behaviors as we have been explaining in our lasts blogs. The microbiota-gut-brain axis may be involved in this process but the mechanisms are not fully identified (1). The supplementation of probiotics can modulate the microbial community and now has been suspected to contribute to ameliorating symptoms of a psychiatric disease with possible influence on social behaviors (2). To date, no randomized controlled trial has been performed to establish feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. This gave us the idea to perform a study to investigate the effects of supplementation with probiotics, working with adults with Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD) which in most cases present high levels of impulsivity, compulsivity and aggression.

Probiotics for healthWe call our project PROBIA, which is an acronym of “PROBiotics for Impulsivity in Adults”. This study will be performed in three centers of Europe including, Goethe University in Frankfurt, Semmelweis University in Budapest and Vall d’Hebron Research Institute (VHIR) in Barcelona, the coordinator of the clinical trial. We are planning to start recruiting patients in January of 2019 and obtain the results in 2021. In our study, we will explore the effects of probiotics by measuring the change in ADHD or BPD symptoms, general psychopathology, health-related quality of life, neurocognitive function, nutritional intake, and physical fitness. The effect of the intervention on the microbiome, epigenetics, blood biomarkers, and health will be also explored by collecting blood, stool, and saliva samples.

We are looking forward to having the results of this amazing study in order to understand the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If improvement effects can be established in these patients, new cost-effective treatment will be available to this population.

 This was co-authored by Josep Antoni Ramos-Quiroga, MD PhD, psychiatrist and Head of Department of Psychiatry at Hospital Universitari Vall d’Hebron in Barcelona, Spain. He is also professor at Universitat Autònoma de Barcelona.

Sources

  1. Desbonnet L, Clarke G, Shanahan F, Dinan TG, Cryan JF. Microbiota is essential for social development in the mouse. Mol Psychiatry [Internet]. The Author(s); 2013 May 21;19:146. Available from: http://dx.doi.org/10.1038/mp.2013.65
  2. Felice VD, O SM. The microbiome and disorders of the central nervous system. 2017 [cited 2017 Oct 16]; Available from: https://ac.els-cdn.com/S0091305717300242/1-s2.0-S0091305717300242-main.pdf?_tid=b52750d8-b2ae-11e7-819b-00000aab0f02&acdnat=1508185089_58e99184d2c0f677d79ff1dd88d02667

 

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What is inflammation?

Inflammation is the response of the body’s immune system against external factors that can put your health in danger. When this system feels it is attacked by something that may harm your health, it activates some molecules that are called cytokines in order to neutralize or avoid any damage so you can be safe.

Why is inflammation bad? What does it do?

Inflammation isn’t bad by itself, since its purpose is to protect our body. In some cases however, when the duration of this response is extended for too long- I’m talking about years- it can cause harmful effects to your health. Especially, it can affect the brain by active transport of cytokines throughout this organ.

Neuro-inflammation may occur if this process continues past early stages. Neuro-inflammation plays an important role in the development of mental diseases such as attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, depression, anxiety, bipolar disorder (BD), and obsessive-compulsive disorder (OCD), where elevated levels of inflammation have been found(1).

What causes inflammation? 

Inflammation can occur by different factors. Some of them could be: pathogens, injuries, chronic stress, and diseases like dermatitis, cystitis or bronchitis to mention a few.

Nutritional factors like overweight and poor diet quality can also trigger this process by increasing fat accumulation in our cells and damaging them (2). The exact mechanisms that are involved in these processes are still in research.

What decreases inflammation?

Research has found that adhering to a healthy diet, like the Mediterranean diet, characterized by high intake of fruit, vegetables, whole grains, fish, lean meats and nuts, can decrease inflammation and protect you against depressive symptoms and anxiety (3,4).

There is evidence that prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) can also help lowering inflammation. In addition, you should avoid eating pro-inflammatory foods that have been found to increase the risk of inflammation, and with it mental disorders. Some of these are refined carbohydrates, beverages with a lot of sugar added like soda, juice and sports drinks, processed meat and foods high in saturated fats (5).

What are anti-inflammatory foods

Anti-inflammatory foods are the contrast of pro-inflammatory foods. These are foods that have been found to promote or induce low levels of inflammation in our body, which may protect us against neurological disorders. Briefly, these foods include fruits, vegetables, olive oil, fish and spices like curcuma (turmeric).

Here’s what YOU can do to minimize inflammation and improve your mental health.

Inflammation and Foods

This was co-authored by Josep Antoni Ramos-Quiroga, MD PhD psychiatrist and Head of Department of Psychiatry at Hospital Universitari Vall d’Hebron in Barcelona, Spain. He is also professor at Universitat Autònoma de Barcelona.

Sources

  1. Mitchell RHB, Goldstein BI. Inflammation in children and adolescents with neuropsychiatric disorders: A systematic review. J Am Acad Child Adolesc Psychiatry [Internet]. Elsevier Inc; 2014;53(3):274–96. Available from: http://dx.doi.org/10.1016/j.jaac.2013.11.013
  2. Ogłodek EA, Just MJ. The Association between Inflammatory Markers (iNOS, HO-1, IL-33, MIP-1β) and Depression with and without Posttraumatic Stress Disorder. Pharmacol Reports [Internet]. 2018;70:1065–72. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1734114017305923
  3. Lassale C, Batty GD, Baghdadli A, Jacka F, Sánchez-Villegas A, Kivimäki M, et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol Psychiatry [Internet]. Springer US; 2018;1. Available from: http://www.nature.com/articles/s41380-018-0237-8
  4. Phillips CM, Shivappa N, Hébert JR, Perry IJ. Dietary inflammatory index and mental health: A cross-sectional analysis of the relationship with depressive symptoms, anxiety and well-being in adults. Clin Nutr. 2017;37.
  5. Shivappa N, Bonaccio M, Hebert JR, Di Castelnuovo A, Costanzo S, Ruggiero E, et al. Association of proinflammatory diet with low-grade inflammation: results from the Moli-sani study. Nutrition. 2018;54:182–8.

 

 

 

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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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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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