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).

 

 

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

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