UnveilMe: Unveiling the role of microbial metabolites in human infant development

Since the last report, four scientific original works have been published. The first work, which focuses on Bacteroides caccae, was accepted for publication in "Applied and Environmental Microbiology," a level 2 journal. In this work, we discovered a strong mother-child association with B. caccae. We also found that a specific strain of B. caccae is globally distributed. Based on the strain's gene composition, it appears to have the ability to induce the production of fucose in the intestine, which it can use as a nutrient source. This may help explain early colonization. The second published work examines the presence of bacteriocins and their possible role in explaining the bacterial diversity in the infant gut. This contributes to our understanding of the early stages of gut flora development and may have implications for child health. In this work, we searched all available data on gut microbiota from both children and adults. This search revealed that bacteriocin genes are more common in the infant gut than in adults. Furthermore, we showed that the presence of bacteriocin genes increased strain diversity. We created an explanatory model based on the rock-paper-scissors principle to explain the relationship between bacteriocins and strain diversity. In the third work published this year, we investigated the relationship between butyric acid, function, and composition of gut microbiota. In this work, we showed that the composition provides a better explanation for the amount of butyric acid than the function of intestinal bacteria itself. This indicates a complex interaction related to butyric acid production, and this interaction is difficult to predict directly from gene composition. In the fourth work accepted for publication, we focus on predicting the composition of immune cells in one-year-olds based on the composition at 6 months. This has the potential to predict health outcomes and understand the development of the immune system in young children. We showed that children could be grouped into four categories based on immunological patterns at one year of age. These groups could then be related to specific bacterial groups present in the children's intestines at 6 months of age. Ongoing activities include a study with approximately 1000 children at 6 and 12 months of age. Based on data from the PreventADALL study, this study seeks to understand the relationship between diet, the composition of short-chain fatty acids, and microbiota composition at the strain level. The results could provide new insights into allergy development in children. In connection with the final phase of the project, we are conducting laboratory experiments with mice to examine the extent to which fucose induction affects the gut flora. By examining mice with and without fucose in the intestine, we are investigating the significance of fucose for the transfer of gut bacteria. The experimental phase of this work is expected to be completed in early 2024. This research will help us understand the interaction between bacteria and the host related to how both microbes and the host develop. Overall, we consider the project to be on track

Humans have evolved as an integral part of the microbial world, and we cannot live without bacterial services. We exploit microbial metabolic capacities in order to produce short chain fatty acids (SCFA), and other essential metabolites. SCFAs are key metabolites for humans, being the main energy source for gut epithelial cells, immune modulation, and glucose production. Microbial exposure during infancy represents a crucial part of a human life, as it is essential for immunological and developmental programming. SCFAs represent the main microbial metabolites that affect infant maturation and immunological development. Recent evidence suggests that there are age-related windows of opportunities for microbial and SCFA exposure during infancy. If these are not met, the result may be aberrant, lifelong cognitive and immunological disorders. This paricularily relates to the two main SCFAs butyrate and propionate. The primary hypothesis in this application is that a shift in the propionate to butyrate ratio during infancy is important for proper immunological- and developmental maturation. This project will address the gut microbiota/SCFA in the transition from an infant- to and adult-like composition and the function. We will focus on SCFAs due to their essential role in gut and immunological maturation. We will further focus on the key SCFA metabolites propionate and butyrate, and the main metabolic pathways of formation. Our analytical approach will first be to establish correlation patterns between SCFA and the microbiota composition and function at different age categories (WP1). Then we will use prior knowledge about metabolic pattern associations to derive mechanistic models related to SCFA metabolism in the infant gut (WP2). Finally, we will test the mechanistic models by in vitro and in vivo experimental studies (WP3-WP5). The project main deliverable will be a mechanistic understanding of SCFAs and microbiota during human infant development/maturation.