MoBa is short for The Norwegian Mother and Child Cohort Study which is a large pregnancy observational study. During the years 1999-2008 pregnant women in Norway were recruited to the study. The study is conducted by the Norwegian Institute of Public Health. Questionnaires regarding health, diet and environment were sent out to the women during and after pregnancy. Women are sent regular follow-up questionnaires. As the child grows up, the child also completes questionnaires. In addition, the fathers were invited to participate with a questionnaire when their partner was pregnant. Biological samples were also collected from the mother, father and child. Today there are 114 500 children, 95 000 mothers and 75 000 fathers participating in the study.
The study was set up to gain knowledge about the causes behind serious disease. The study is unique because it gathers information from fetal (in vitro) life and follows the offspring into adulthood. In this manner it is possible to look at early influences and later disease. The study is prospective, which means that information about mothers, fathers and their offspring is registered before a disease has manifested itself. With this design, women are asked questions several times during her pregnancy and do not have to try to remember what she did when looking back at her pregnancy.
MoBa is population-based and became nationwide with 50 participating hospitals in Norway. For more information on the many publications based on MoBa data, visit this link:
Recently, I participated in the Radboud Talks 2019, a scientific pitch competition, where I was lucky to be one of the eight finalists.
Why Radboud Talks? It is a perfect opportunity to share my work/ideas with the world and to gain more experience regarding presentation skills. They organized two workshops beforehand, where I had the opportunity to learn presentation techniques from professionals (actors and science communication advisors). We also received a lot of feedback, so I really learned a lot about how to present my scientific work to a general audience.
Below you can find the video from the preliminaries based on which I was chosen as a finalist. There you can hear about my research project which is about gut bacteria and their potential role in ADHD (Attention Deficit Hyperactivity Disorder). ADHD is a common worldwide neurodevelopmental disorder. Every person with ADHD has a unique combination of symptoms and challenges. Importantly, it has a significant social impact on patients’ lives, causing disruption at school, work and relationships. Despite its societal importance, progress in understanding disease biology has been slow.
The study of the human microbiome has become a very popular topic, because of their revealed importance in human physiology and health maintenance. Numerous studies have reported that gut bacteria may have an effect on our mental health. Some studies showed a potential role of gut bacteria in a psychiatric disorder like depression, autism or Parkinson (1). Above all, diet showed to have a profound effect of ADHD symptoms. This was earlier described in this blog: https://newbrainnutrition.com/investigating-the-effects-of-a-dietary-intervention-in-adhd-on-the-brain/ and we know that diet is one of the main factors influencing gut bacteria. Taking all together, I am curious (and investigating) if gut bacteria play a role in ADHD and if yes what kind of effect do they have on ADHD symptoms.
REFERENCES: Bastiaanssen, T., Cowan, C., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2018). Making Sense of … the Microbiome in Psychiatry. The international journal of neuropsychopharmacology, 22(1), 37–52. doi:10.1093/ijnp/pyy067
Recent research (1,2) on children and adolescents has reported that elevated levels of ADHD symptoms are positively associated with unhealthy dietary habits, including a higher consumption of refined sugars, processed food, soft drink, instant noodles, and a lower intake of vegetables and fruits. However, the link between low-quality diets and risk of ADHD in adults is still not well established, which would be further explored in the ongoing Eat2beNICE research project.
What is the underlying mechanism for an association between ADHD and unhealthy dietary habits? There is still no clear answer. Nemours’ potential biological pathways, by which dietary intake could have an impact on mental health, has been proposed in the literature (2). For example, iron and zinc are cofactors for dopamine and norepinephrine production (essential factors in the etiology of ADHD), so unbalanced diet with lower levels of iron and zinc may further contribute to the development of ADHD. However, we cannot overlook the possibility of a bi-directional relationship between diet quality and ADHD, especially when the interest in the concept of “food addiction” has received increased attention.
Food addiction refers to being addicted to certain foods (e.g. highly processed foods, highly palatable foods, sweet and junk foods) in a similar way as drug addicts are addicted to drugs. Animal models (3) have suggested that highly processed foods may possess addictive properties. Rats given high-sugar or high-fat foods display symptoms of binge eating, such as consuming increased quantities of food in short time periods, and seeking out highly processed foods despite negative consequences (e.g. electric foot shocks). One human study (4) found that individuals with high levels of ADHD-like traits (e.g. high levels of impulsively, disorganised, attention problems) were more likely to suffer from problematic eating behaviour with overconsumption of specific highly palatable foods in an addiction-like manner. Therefore, food addiction may, just as substance abuse, be over-represented among individuals with ADHD.
Thus, it seems there could be a vicious cycle between unhealthy dietary habits and ADHD: ADHD may lead to a worse choice of diet, lowering the health quality, which could eventually exacerbate ADHD symptoms. We will further test the bidirectional diet-ADHD associations in the ongoing Eat2beNice project.
This was co-authored by Henrik Larsson, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.
Lin Li, MSc, PhD student in the School of Medical Science, Örebro University, Sweden.
Henrik Larsson, PhD, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.
1. Kim KM, Lim MH, Kwon HJ, Yoo SJ, Kim EJ, Kim JW, et al. Associations between attention-deficit/hyperactivity disorder symptoms and dietary habits in elementary school children. Appetite. 2018;127:274-9.
2. Rios-Hernandez A, Alda JA, Farran-Codina A, Ferreira-Garcia E, Izquierdo-Pulido M. The Mediterranean Diet and ADHD in Children and Adolescents. Pediatrics. 2017;139(2).
3. Gearhardt AN, White MA, Potenza MN. Binge Eating Disorder and Food Addiction. Curr Drug Abuse Rev. 2011;4(3):201-7.
A little while ago, this blog featured an entry by Annick Bosch on the TRACE study, an amazing intervention study using the Elimination Diet to treat ADHD in kids (https://newbrainnutrition.com/adhd-and-elimination-diet/). Very shortly summarized, the Elimination Diet entails that participants can only eat a very restricted set of foodstuffs for several weeks, which can greatly reduce the number of ADHD symptoms in some kids. Subsequently, new foodstuffs are added back into the diet one by one, all the time checking that ADHD symptoms do not return. This ensures that every child for which the Elimination Diet proves successful ends up with a unique diet which suppresses their ADHD symptoms.
Now this is a fascinating study, since it indicates a direct influence of diet on ADHD behavior. What we know from the neurobiology of ADHD, is that it is caused by a myriad of relatively small changes in the structure, connectivity and functioning of several brain networks 1. For the most common treatments of ADHD, like medication with methylphenidate 2, we can quite accurately see the changes these interventions have on brain functioning. However, for the Elimination Diet, this has not been studied before at all. This is why we are now starting with the TRACE-MRI study, where kids that participate in a diet intervention in the TRACE program, are also asked to join for two sessions in an MRI scanner. Once before the start of the diet, and once again after 5 weeks, when the strictest phase of the Elimination Diet concludes. In the MRI scanner, we will look at the structure of the brain, at the connectivity of the brain, and at the functioning of the brain using two short psychological tasks. We made a short vlog detailing the experience of some of our first volunteers for this MRI session.
With the addition of this MRI session, we hope to be able to see the changes in brain structure and function over the first 5 weeks of the diet intervention. This will help us establish a solid biological foundation of how diet can influence the brain in general, and ADHD symptoms specifically. It can also show us if the effect of the Elimination Diet is found in the same brain networks and systems which respond to medication treatment. And lastly, we can see if there is a difference in the brains for those participants for whom the diet has a strong effect versus those where the diet does little or nothing to improve their ADHD symptoms. This can then help us identify for which people a dietary intervention would be a good alternative to standard treatment.
We will update you on the TRACE-MRI study and on the developments in this field right here on this blog!
Faraone, S. V et al. Attention-deficit/hyperactivity disorder . Nat. Rev. Dis. Prim. 1, (2015).
Konrad, K., Neufang, S., Fink, G. R. & Herpertz-Dahlmann, B. Long-term effects of methylphenidate on neural networks associated with executive attention in children with ADHD: results from a longitudinal functional MRI study. J. Am. Acad. Child Adolesc. Psychiatry 46, 1633–41 (2007).
Have you ever noticed that the type of food you eat can affect how you feel afterwards? Some food might make you wish to rest and relax, some food might give you the little extra energy you just needed. Evidence is accumulating that also in the long run, diet may play a pivotal role for your mental health. For example, it might have an effect on impulsive and compulsive behaviour .
But it’s not only the diet that affects our body, mind and brain – it’s also the amount of what we eat. Research shows that people don’t necessarily know what a suitable amount of food might be. Sure you can imagine that this can easily lead to obesity – which in turn can impair our general health.
A meta-analysis (that is, a study that investigates an effect among many independent studies that have been conducted so far) from 2018 came to the conclusion that serving size and the size of the tableware has an effect on the amount we eat: When offered larger-sized portions, packages or tableware, participants ate or drank more than when offered smaller-sized versions .
British nutritional scientists now developed a guideline for the British Nutrition Foundation (BNF) to help people estimate the suitable serving size. For example, they recommend that when having a pasta dish, you should take as much pasta for one person as fits into both of your hands (before cooking). A portion of fish or meat should be about half the size of your hand. However, this does not mean that when you eat more than one portion, you are an overeater.
According to their tipsheets, which can be found here, https://www.nutrition.org.uk/healthyliving/find-your-balance/portionwise.html
one should compose his or her daily menu based on a mixture of different portions. For example, 3-4 portions of starchy carbohydrates (such as the above-mentioned pasta) are recommended daily. Their guidelines, however, offer a few handy (literally!) advises to help you get a sense of how much food you should consume, thus preventing you from overeating. With a few simple tips kept in mind, you can do some good for your physical and mental health, daily.
 Hollands GJ, Shemilt I, Marteau TM, Jebb SA, Lewis HB, Wei Y, Higgins JPT,
Ogilvie D. Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco. Cochrane Database of Systematic
Reviews 2015, Issue 9. Art. No.: CD011045. DOI: 10.1002/14651858.CD011045.pub2
View here: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011045.pub2/full
Increasing evidence is showing that the gut microbiota can alter the brain and behavior, and thus may play a role in the development of psychiatric and neurodevelopmental disorders, such as autism and schizophrenia.
Animal models are a useful tool to study this mechanism. For example, germ-free (GF) mice, which have never been exposed to microorganisms, are compared with mice exposed to microorganisms, known as conventional colonized mice (CC). Recent studies have reported that GF animals show increased response to stress, as well as reduced anxiety and memory. In most cases, these alterations are restricted to males, in which there are higher incidence rates of neurodevelopmental disorders compared with females.
Mice, like humans, are a social species and are used to study social behavior. A recent study compared GF and CC mice using different sociability tests. GF mice showed impairments in social behavior compared with CC mice, particularly in males. Interestingly, they demonstrate that social deficits can be reversed by bacterial colonization of the GF gut (GFC), achieving normal social behavior.
Microbiota seem to be crucial for social behaviors, including social motivation and preference for social novelty. Microbiota also regulate repetitive behaviors, characteristic of several disorders such as autism and schizophrenia.
Bacterial colonization can change brain function and behavior, suggesting that microbial-based interventions in later life could improve social impairments and be a useful tool to effect the symptoms of these disorders.
This blog was co-authored by Noèlia Fernàndez and Judit Cabana
Real time measurements of intestinal
gases: a novel method to study how food is being digested
Researchers in Wageningen (The
Netherlands), have been able to identify for the first time, how gut microorganisms
process different types of carbohydrates by measuring in real time the intestinal
gases of mice. This is not only a novel method to understand how food is
digested but could also tell us more about the role of gut microorganisms in
The intestinal microbiota is a diverse and
dynamic community of microorganisms which regulate our health status. The
advancement of biomolecular techniques and bioinformatics nowadays allows
researchers to explore the residents of our intestines, revealing what type of microorganisms
are there. However, studying only the microbial composition of an individual
provides limited insights on the mechanisms by which microorganisms can
interact with the rest of our body. For example, far less is understood about
the contribution of the gut microorganisms in the production of intestinal
gases such as hydrogen, methane and carbon dioxide through the breakdown of
food and how these gases affect the biochemical pathways of our bodies.
Intestinal gases consist mostly of
nitrogen, and carbon dioxide, which originate primarily from inhaled air. Hydrogen
and methane though, are produced as by-products of carbohydrate fermentation
(break down), by intestinal microorganisms. However, not all carbohydrates are
digested in the same way. For instance, food with simple sugars can be rapidly absorbed
in the small intestine unlike complex carbohydrates such as fibers, which reach
the colon where they are digested by the colonic microbiota.
Measuring hydrogen in mouse intestines
To study these interactions and gain
knowledge on how microorganisms process carbohydrates, the research team led by Evert van
Schothorst from the Human and Animal Physiology Group of Wageningen University
(WU) in collaboration with the WU-Laboratory of Microbiology fed mice two
different diets with the same nutritional values but with different types of carbohydrates
(1). The first diet contained amylopectin,
a carbohydrate which can be digested readily in the small intestine while the
second diet contained amylose, a slowly digestible carbohydrate that is
digested by intestinal microorganisms in the colon.
Animals fed the easily digestible carbohydrates
showed minimal production of hydrogen whereas the group fed with the complex
carbohydrates presented high levels of hydrogen. Moreover, the two groups were
characterized not only by distinct microbial composition (different types of
bacteria present) but also distinct metabolic profiles (short chain fatty acids),
suggesting that the type of carbohydrate strongly affects microbial composition
The importance of
Hydrogen consumption is essential in any anoxic
(without oxygen) microbial environment to maintain fermentative processes. In
the intestine it can be utilised through three major pathways for the
production of acetate, methane and hydrogen sulphide. These molecules are
critical mediators of gut homeostasis, as acetate is the most predominant short
chain fatty acid produced in mammals with evidence suggesting a role in inflammation and obesity (2). Methane, which is produced by a specific type of microorganisms,
called archaea, has been associated with constipation related diseases, such as
irritable bowel syndrome(3) and also recently with athletes’ performance (4)! Finally hydrogen sulphide
is considered to be a toxic gas, although recent findings support the notion
that it also has neuroprotective effects in neurodegenerative disorders such as Parkinson and Alzheimer diseases (5).
To the best of our knowledge, this is the first time that food-microbiota interactions have been studied continuously, non-invasively and in real time in a mouse model. Hydrogen is a critical molecule for intestinal health and understanding its dynamics can provide valuable information about intestinal function, and deviations in conditions such as Crohn’s disease or irritable bowel syndrome (IBS).
1. Fernández-Calleja, J.M., et al., Non-invasive continuous real-time in vivo analysis of microbial
hydrogen production shows adaptation to fermentable carbohydrates in mice.
Scientific reports, 2018. 8(1): p.
Perry, R.J., et al., Acetate mediates a
microbiome–brain–β-cell axis to promote metabolic syndrome. Nature, 2016. 534(7606): p. 213
3. Triantafyllou, K., C. Chang, and M. Pimentel, Methanogens, methane and gastrointestinal
motility. Journal of neurogastroenterology and motility, 2014. 20(1): p. 31.
4. Petersen, L.M., et al., Community characteristics of the gut microbiomes of competitive
cyclists. Microbiome, 2017. 5(1):
Y.O., Provotella‐derived hydrogen sulfide, constipation,
and neuroprotection in Parkinson’s disease. Movement Disorders, 2015. 30(8): p.
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.
Why 12 genetic markers for ADHD are exciting news for New Brain Nutrition
We are finally here: for the first time, genome-wide significant markers are identified that increase the risk for Attention Deficit / Hyperactivity Disorder (ADHD). This research was conducted by an international consortium of more than 200 experts on genetics and ADHD, and includes several researchers that are also involved in our Eat2beNICE project (the scientific basis of this New Brain Nutrition website). The findings were recently published in the prestigious journal “Nature Genetics” and will greatly advance the field of ADHD genetics research.
Why is this finding so important?
The genetics of ADHD are very complex. While ADHD is highly heritable, there are likely to be thousands of genes that contribute to the disorder. Each variant individually increases the risk by only a tiny fraction. To discover these variants, you therefore need incredibly large samples. Only then can you determine which variants are linked to ADHD. The now published study by Ditte Demontis and her team combined data from many different databases and studies, together including more than 55,000 individuals of whom over 22,000 had an ADHD diagnosis.
We can now be certain that the twelve genetic markers contribute to the risk of developing ADHD. Their influence is however very small, so these markers by themselves can’t tell if someone will have ADHD. What’s interesting for the researchers is that none of these markers were identified before in much smaller genetic studies of ADHD. So this provides many new research questions to further investigate the biological mechanisms of ADHD. For instance, several of the markers point to genes that are involved in brain development and neuronal communication.
Why are our researchers excited about this?
A second important finding from the study is that the genetic variants were not specific to ADHD, but overlapped with risk of lower education, higher risk of obesity, increased BMI, and type-2 diabetes. If genetic variants increase both your risk for mental health problems such as ADHD, and for nutrition-related problems such as obesity and type-2 diabetes, then there could be a shared biological mechanism that ties this all together.
We think that this mechanism is located in the communication between the gut and the brain. A complex combination of genetic and environmental factors influence this brain-gut communication, which leads to differences in behaviour, metabolism and (mental) health.
The microorganisms in your gut play an important role in the interaction between your genes and outside environmental influences (such as stress, illness or your diet). Now that we know which genes are important in ADHD, we can investigate how their functioning is influenced by environmental factors. For instance, gut microorganisms can produce certain metabolites that interact with these genes.
The publication by Ditte Demontis and her co-workers is therefore not only relevant for the field of ADHD genetics, but brings us one step closer to understanding the biological factors that influence our mental health and wellbeing.
Demontis et al. (2018) Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics. https://www.nature.com/articles/s41588-018-0269-7
The first author of the paper, Ditte Demontis, also wrote a blog about the publication. You can read it here: https://mind-the-gap.live/2018/12/10/the-first-risk-genes-for-adhd-has-been-identified/
Breaking news: It has long been assumed that the gut and the brain communicate not only via a slow, hormonal pathway, but that there must be an additional, faster association between gut and brain. Melanie Maya Kelberer and her colleagues from Duke University, NC, now managed to detect this connection. Their paper has just been published in the renowned journal ‘Science’.
By researching a mouse model, they were able to show that the gut and the brain are connected via one single synapse. This is how it works: A cell in the gut (the so-called enteroendocrine cell) transfers its information to a nerve ending just outside the gut. At the connecting nerve ending (the synapse), the neurotransmitter glutamate – the most important excitatory transmitter in the nervous system – passes on the information about our nutrition to small nerve endings of the vagal nerve, which spreads from the brain to the intestines.
By travelling along this vagal nerve, the information from the gut reaches the brainstem within milliseconds. The authors now state that a new name is needed for the enteroendocrine cells, now that they have been shown to be way more than that. The name ‘neuropod cells’ has been suggested. The authors interpret their findings as such, that this rapid connection between the gut and the brain helps the brain to make sense of what has been eaten. Through back-signalling, the brain might also influence the gut. In sum, this finding is an important step towards a better understanding of how the gut and the brain communicate. Findings such as this one help us to find ways to positively influence our brain states and our mental health by our food choices.
Read the original paper here: http://science.sciencemag.org/content/361/6408/eaat5236.long
Kaelberer, M.M., Buchanan, K. L., Klein, M. E., Barth, B. B., Montoya, M. M., Shen, X., and Bohórquez, D. V. (2018), A gut-brain neural circuit for nutrient sensory transduction, Science,
Vol. 361, Issue 6408
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