Professor El-Omar has selected Professor Tine Jess to do the next #GUTBlog. Professor Jess is Director of the National Center of Excellence for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, at Aalborg University, Copenhagen, Denmark. She is MD from University of Copenhagen, DMSc from University of Copenhagen and Mayo Clinic, Minnesota, and Fellow of the Royal Danish Academy of Sciences and Letters. Professor Jess’ research focuses on the molecular epidemiology of inflammatory bowel disease.

The #GUTBlog focusses on the Recent advances in basic science paper “Early-life exposures and the microbiome: implications for IBD prevention” which was published in paper copy in GUT in March 2024. She co-authored the paper with Assistant Professor Lin Zhang, Dr Manasi Agrawal and Professor Siew Ng.

Professor Jess writes:

“Globally, millions of people suffer from inflammatory bowel disease (IBD) and the incidence is on the rise, especially in countries adopting a westernized lifestyle.

In the Western world, almost twice as many young people are diagnosed with IBD than with type 1 diabetes.
The speed with which the incidence of IBD increases cannot be explained by genetics alone, i.e. that IBD is an inherited disease. In fact, only 10% of IBD patients have a family member with IBD.

Hence, we need to search for environmental factors that impact our health, potentially through our gut microbiome, to understand the rapidly increasing occurrence of these diseases. Such environmental factors are likely at play early in life.
We wondered if it was possible to identify specific maternal and offspring exposures that impose harmful effects on our intestinal health and thereby our risk of IBD. Identifying such factors would take us a crucial step towards prevention of these serious diseases.

To answer this question, we went through the world literature, identifying more than 150 studies representing different parts of the puzzle.

This search clearly demonstrated our hypothesis that the early-life period represents a window of opportunity for modulation of our gut microbiome and our immune function, which may help us avoiding disease later in life.

The development of our gut microbiome starts at birth with a bacterial community acquired from our mother. This community reflects the health of the mother and her exposures. When a child grows and is exposed to diet, the surrounding environment and antibiotics, the microbiome gradually changes and by age 2, the child’s microbiome starts resembling an adult microbiome.
The child’s early gut microbiome thereby represents a dynamic microbial ecosystem under great influence from external factors. This ecosystem in turn influences the development of the child’s immune system and metabolism, and consequently also the child’s later health.

Therefore, we should think of the microbiome as a mirror of what both the mother and child are exposed to, which in mothers are factors such as weight-changes during pregnancy, stress, low-fibre diet, smoking, exercise, sleep, gestational diabetes, and depression. Even mode of delivery plays a role, as Cesarian section will cause less vertical transfer of microbes and therefore greater dissimilarity in the microbiome between mother and infant.

But how does the gut microbiome impact disease risk? We find that the imbalance of the gut microbiome in patients with IBD bear striking resemblance to the gut microbiome changes induced by early-life disturbances. And we know that these changes influence the immune system, which is crucial in IBD development.

We also find that epidemiological studies corroborate these similarities. The same factors that influence microbiome development have been found to be linked to IBD development, including maternal health, prenatal and perinatal exposures, birth month, breast feeding, hygiene, immigration, antibiotics, infections and passive smoking.

We propose that development of IBD is a ‘multiple hits’ process, where things that happen during early life may lead to changes in the gut microbiome and in the immune system making an individual susceptible to IBD, and that later exposures may lead to actual onset of disease.

Thus, if we want to prevent IBD from happening, one important step is to maintain a healthy gut microbiome.
We find that several things can be done early in life to help our gut microbiome develop in a beneficial way. It is key to reduce the use of antibiotics and avoid exposure to smoke from tobacco. But there are also more proactive positive things you can do, such as healthy eating and encouraging breast feeding and greenspace exposure.

Most importantly, ensuring a healthy gut microbiome early in life is likely to have a positive impact on our health, minimising the risk of many chronic immune-mediated conditions.”

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@linzhang8385

@manasiagrawalmd

@PREDICTIBD

@DrTineJess

@Siew_C_Ng