Project results: What is the impact of maternal obesity on the offspring in later life?

Obesity affects almost 30% of all pregnant women. Maternal obesity is associated with lower cognitive abilities and behavioural disorders in the offspring. Also gut microbiota influence brain function. Early life is found to be fundamental for brain and microbiota development. Maternal obesity affects maturation of gut microbiota and is an important predictor of cognitive dysfunction in the offspring. Since the burden of cognitive dysfunction is increasing due to aging population and the growing occurrence of predisposing conditions (metabolic diseases, unhealthy diets), strategies are needed to (partly) prevent cognitive decline already in early life.

In the past 4 years (2018-2022), the ‘Maternal obesity and cognitive dysfunction in the offspring: cause-effect role of the GUT MicrobiOMe and early dietary prevention (GUTMOM) project investigated the impact of obesity in pregnant women on the cognition and metabolism of their offspring later in life. Research groups from Italy, Spain, the Netherlands, Germany were involved in the project. Three additional partners from Finland, Italy, the Netherlands participated with their own resources. The project was cofunded by the European Commission within the HDHL-INTIMIC cofunded call.

Aims

The project focused on maternal obesity and cognitive dysfunction in offspring and the relationship that gut microbiota holds between these two areas. The aim was to evaluate whether the negative effects of maternal obesity on cognitive function in the offspring are partly mediated by the microbiota and its metabolites, potentially offering the opportunity for non‐invasive risk‐screening and risk‐reduction by tailored foods and diets, since earliest life stages. GUTMOM used two existing children cohorts to identify the gut bacteria and metabolites that are related to maternal obesity and offspring’s cognitive development in early, pre-scholar and scholar age. Mice were used to investigate cause-effect mechanisms, and develop tailored dietary interventions to counteract the effects of maternal obesity on the gut microbiota improving offspring’s cognition. Also, the effect of early life stress on the offspring gut microbiome composition and cognitive function was studied, by limiting nesting and bedding material of the mother mice, making it challenging for them to take proper care of their offspring. 

GUTMOM vlog

As part of the JPI HDHL conference in 2019, a science vlog (video log) contest for early career scientists was organised. Lea Brix, early career scientist within the GUTMOM project, won the contest. Watch the vlog on our Youtube channel.

Results

The researchers have not been able to establish direct or strong correlations between cognition and gut microbiome composition, but they did make some other observations regarding the functioning of the gut microbiome. For example, there were big differences in the composition of the intestinal microbiome immediately after birth compared to subsequent periods. They also found that children whose mothers were overweight during pregnancy have a different microbiome composition. Although they were not able to establish a direct link between gut microbiota and cognitive functions of the children per age phase, they did see that cognitive ability measured in three-year-old children is slightly higher in those children whose mothers had a healthy weight during pregnancy. Finally, it was observed that specific bacteria in the first stool of new-borns, namely Bifidobacterium and Veillonella, appear to be predictive of the development of cognitive skills later in life in five-year-old children.

From the experiments in mice the researchers conclude that maternal high-fat diet (58% kcal from fat) during gestation affects cognition and emotion in the adult offspring, rather than maternal obesity. This suggest that diet quality might be more relevant than body weight. In addition, another key conclusion was that  exposure to early life stress may be an important early disruptor of the microbiota and its function. This could pave the way for exploring interventions that actually target underlying causes of maternal stress which in turn can have an affect on dietary quality and obesity.

Overall, the GUTMOM project provided new perspectives in the prevention and treatment of cognitive decline and neurodevelopmental disorders in children.

In total, 11 projects were funded within the HDHL-INTIMIC cofunded call. All results will be shared on our website. Stay tuned! See ‘more information’ below for already published project results. 

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