In my previous blogs, I explained the research questions of my study. This study will be performed in two cohorts which I will elaborate on in this current blog about early life nutrition and studying gut microbiota. The cohorts are called BIBO and BINGO.
BIBO stands for ‘Basale Invloeden op de Baby’s Ontwikkeling’ (in English: basal influences on infant’s development). Recruitment of this cohort started in 2006, and a total of 193 mothers and their infants were included. At age 10, 168 mothers and their children still joined the BIBO study; the attrition rate is thus low. The majority of the mothers are highly educated (76%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. A unique aspect of the BIBO study is the number of stool samples collected in early life. Also, detailed information about early life nutrition has been recorded during the first six months of life (e.g. information on daily frequency of breastfeeding, formula feeding, and mixed feeding). Together, these stool samples and nutrition diaries provide important insights in the relations between early life nutrition and gut microbiota development. Data about children within the BIBO cohort will be collected at age 12,5 years and 14 years. At 12,5 years, the participants will be invited to the university for an fMRI scan (more information about the fMRI scan will be given in a future blog). At age 14, children’s impulsive behavior will be assessed by means of behavioral tests and (self- and mother-report) questionnaires.
BINGO stands for ‘Biologische INvloeden op baby’s Gezondheid en Ontwikkeling’ (in English: biological influences on infant’s health and development). When investigating biological influences on infant’s health and development, it is important to start before birth. Therefore, 86 healthy women were recruited during pregnancy. Recruitment took place in 2014 and 2015. One unique property of the BINGO cohort is the fact that not only mothers were recruited, but also their partners. The role of fathers is often neglected in research, and thus an important strength of this BINGO cohort. Another unique property is that samples of mothers’ milk were collected three times during the first three months of life, to investigate breast milk composition. As for many infants their diet early in life primarily consists of breast milk, it is interesting to relate breast milk composition to later gut microbiota composition and development. Currently, 79 mothers and children, and 54 fathers are still joining the BINGO study. The average age of the participants at the time of recruitment was 32 years for mothers and 33 years for the father. Majority of the parents within this cohort are highly educated (77%) and from Dutch origin (89%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. At age 3, children’s impulsive behavior will be assessed by means of behavioral tests and mother-report questionnaires.
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.
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.
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).
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).
Julvez, J. et al. Attention behaviour and hyperactivity at age 4 and duration of breast-feeding. Acta Paediatr.96, 842–847 (2007).
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).
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).
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).
Lewis, Z. T. et al. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome3, 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.
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
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
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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