The Gut Microbiome, The Brain, and Cognitive Development in Infants

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Athanasia Ioannou
About the Author

Athanasia Ioannou is a PhD candidate at Wageningen University, The Netherlands. She works on the PRIDE (PRegnancy and Infant Development) dataset, with an interest in how the infant gut microbiome contributes to socioemotional cognitive development.

Lieke Haanstra
About the Author

Lieke Haanstra is a MSc student at Wageningen University, The Netherlands. She works on the PRIDE (PRegnancy and Infant Development) dataset, with an interest in how the infant gut microbiome contributes to socioemotional cognitive development.

The gut microbiome is activated at birth

Humans are capable of complex activities such as decision-making, using tools and forming societies. The human body consist of 30 trillion cells that have differentiated to give each body part its unique properties. Human cells are the pillars that enabled man to go to the moon, design massive computers, genetically modify plants, eradicate diseases and reach the golden age of mean 85.7 years. But let us tell you the truth: this is only half the story!

The human body is home to 39 trillion bacteria that, collectively with other microbes, are called our microbiome.1 So, does that mean that we are the shelter of a bacterial blob? Before you fall into existential crisis, we will explain why these bacteria are so important and how they shape you from the day you are born.

The birth of the gut microbiome

The moment you take your first breath signifies a milestone, for you and your family. It is also a milestone for your microbiome because it is the moment that the first bacteria touch your skin and enter your gastrointestinal tract. If you are delivered via vaginal birth, a mix of bacteria from your mother’s colon and vagina will come in contact with you. Now, your inner hypochondriac may be uncomfortable with what was just described, but the truth is, it is very crucial that these bacteria end up swallowed. They then travel to your lower gut where they are the first to inhabit an uncharted territory: the gut. From that moment on, the story becomes more complicated.

Bacteria are actually a lot like humans. They need food and, often, they are quite picky about what they eat.2 Sometimes, they even share their food or they stick with the fellow that can give them their preferred snack. They interact with one another, and they form a community. Also, changes in their environment, such as your diet, have an effect on members of the community. The way you are born, your feeding mode, your environment, medication and other health related issues greatly affect the bacterial communities in your gut.3

This relationship with your gut microbiome is a two-way street. Not only you affect it, but it also affects you.4 Did you know that these bacteria can eat the fibers you cannot digest and give you almost 10% of your daily energy intake? As a baby, the functionality of the gut microbiome also has lifelong effects. The interplay between the microbiome and the gut trains your immune system so that it recognizes friends from foes.

Gut-brain talk

The bacteria in your gut also connect with your brain.5 Bacteria have been found to produce hundreds of compounds that affect brain-related activities like mood, behavior or hormones. Certain factors, like diet and medications, that are associated with a healthy gut microbiome are also related to better cognitive development.6–8

Could it be that your gut microbiome is responsible for your mood swings?9 Or predisposes you to Alzheimer’s or Parkinson’s disease?10,11 Could it affect pain perception12 or your susceptibility to certain medicines?13 There are indications for these relationships, however, we still cannot give a definite answer to these questions.

To understand the intricate interplay between the gut microbiome and disease, we first need to understand how the microbiome evolves and matures in healthy individuals. That is why we are now investigating  the trajectory of the gut microbiome in the first year of life, in healthy infants followed from pregnancy until, at least, the age of 2 years. This data is part of the PRegnancy and Infant DEvelopment (PRIDE) Study of the Radboud University Medical Center Nijmegen, in the Netherlands. In our research project, the groups of Alejandro Arias Vasquez (Radboudumc Nijmegen) and Clara Belzer (Wageningen University) join forces. With the results of the PRIDE study we aspire to connect the gut microbiome with the socio-emotional cognitive development in infants, but also pave the way towards novel opportunities for health improvement.

References

1.           Ursell, L. K., Metcalf, J. L., Parfrey, L. W. & Knight, R. Defining the human microbiome. Nutr. Rev. 70, S38–S44 (2012).

2.           Zhang, N., Ju, Z. & Zuo, T. Time for food: The impact of diet on gut microbiota and human health. Nutrition 5152, 80–85 (2018).

3.           Hasan, N. & Yang, H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ 7, e7502 (2019).

4.           Visconti, A. et al. Interplay between the human gut microbiome and host metabolism. Nat. Commun. 10, 4505 (2019).

5.           Dinan, T. G. & Cryan, J. F. Brain–gut–microbiota axis — mood, metabolism and behaviour. Nat. Rev. Gastroenterol. Hepatol. 14, 69–70 (2017).

6.           Strøm, M. et al. Is breast feeding associated with offspring IQ at age 5? Findings from prospective cohort: Lifestyle During Pregnancy Study. BMJ Open 9, e023134 (2019).

7.           Quigley, M. A. et al. Breastfeeding is Associated with Improved Child Cognitive Development: A Population-Based Cohort Study. J. Pediatr. 160, 25–32 (2012).

8.           Minter, M. R. et al. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1ΔE9 murine model of Alzheimer’s disease. Sci. Rep. 7, 10411 (2017).

9.           Huang, T. T. et al. Current Understanding of Gut Microbiota in Mood Disorders: An Update of Human Studies. Front. Genet. 10, (2019).

10.        Tran, T. T. T. et al. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology. FASEB J. 33, 8221–8231 (2019).

11.        Unger, M. M. et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat. Disord. 32, 66–72 (2016).

12.        Shiro, Y., Arai, Y. C., Ikemoto, T., Ueda, W. & Ushida, T. Correlation Between Gut Microbiome Composition and Acute Pain Perception in Young Healthy Male Subjects. Pain Med. 22, 1522–1531 (2021).

13.        Clayton, T. A., Baker, D., Lindon, J. C., Everett, J. R. & Nicholson, J. K. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc. Natl. Acad. Sci. 106, 14728–14733 (2009).